Abstract: Leprosy is characterized by spectrum of histologically different granulomatous skin lesions that reflects the patient's immune response to Mycobacterium leprae. Presence, frequency, and distribution of both CD4+ CD25+ FoxP3+ T regulatory cells (T-regs) and CD123+ plasmacytoid dendritic cells in leprosy have never been investigated. We performed a retrospective immunohistochemical study on 20 cases of leprosy [tuberculoid tuberculoid (TT): 1 patient; borderline tuberculoid (BT): 3 patients; borderline lepromatous (BL): 5 patients; lepromatous lepromatous (LL): 5 patients; borderline borderline in reversal reaction (BB-RR): 1 patient; BT-RR: 2 patients; and erythema nodosum leprosum (ENL): 3 patients]. FoxP3-positive cells were present in 95% of the cases with an average density of 2.9% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was no statistical difference of FoxP3 expression between TT, BT, BL, and LL, whereas a statistical significant increment (P = 0.042) was observed in patients affected by reversal leprosy reactions (BT-RR and BB-RR) compared with patients affected by ENL and patients with nonreactional disease forms (BL, LL, BT, TT). CD123 expression was not observed in any of the biopsy specimens evaluated; with the exception of 2 cases of ENL, in which a focal positivity for CD123 was observed. Our results show that plasmacytoid dendritic cells are not involved in the immune response against M. leprae while T-regs are present in leprosy skin lesions. These data raise the question if T-regs have a pathogenetic role in HD as previously demonstrated in Leishmania major and Mycobacterium tuberculosis.
Abstract: In the present study, we report the occurrence of Lyme's borreliosis in patients from the Brazilian Amazon Region. Borreliosis was investigated by immunohistochemistry and focus floating microscopy for Borrelia burgdorferi in skin biopsy samples from 22 patients with both clinical and histopathology evidences compatible with Erythema Migrans. Spirochetes were detected by specific immunohistochemistry and focus floating microscopy for Borrelia burgdorferi in samples from five patients. Clinical cure of the cutaneous lesions was observed in all the patients after treatment with doxycycline regimen as proposed by the Center Disease Control guidelines. A limitation of our study was the fact that we were not able to isolate and culture these organisms. These are the first known Brazilian cases of borreliosis to have Focus Floating Microscopy confirmation.
Abstract: Teledermoscopy has become in the last years one of the most florid reality of teledermatology. Parallel to the achievement of dermoscopy in clinical settings, teledermoscopy has grown in different fields, namely tele-education and teleconsulting. Blogs, atlases, discussion forums, on line courses and Diploma Courses do not only offer a second opinion consultation but give the opportunity to residents in dermatology and dermatologists with different level of expertise in dermoscopy to easily learn at home, to train or to improve their level in dermoscopy. On the other side, in some countries demand for melanoma screening has led to commercialization of "teledermoscopy" by different companies. Images nowadays can be transmitted over telecommunication networks not only via e-mail or a specific web application but also with last generation cellular phones. This reality opens the new incoming field of mobile teledermatology. Mobile teledermoscopy is a new horizon that might become in the future the basis of the self examination of pigmented skin lesions as a screening tool for malignant cutaneous tumors or to follow-up of high risk patients.
Abstract: BACKGROUND: Thrombocytopenia has been reported to be associated with efalizumab therapy, but has only sporadically been reported with other anti-tumor necrosis factor alfa (TNF-alpha) agents. OBJECTIVE: To describe the frequency of thrombocytopenia in a cohort of patients who underwent biological therapies for psoriasis. METHODS: This was a retrospective observational study of 93 patients. RESULTS: One hundred eighteen courses of biological therapies were administered to 93 patients. Four of 67 patients who received anti-TNF-alpha agents developed drug-induced thrombocytopenia during treatment, compared with none of the 51 patients receiving efalizumab therapy. The platelet count recovered after suspension of anti-TNF-alpha agents in 3 patients and relapsed after re-exposure in two patients. The overall estimated frequency of thrombocytopenia in our cohort was 4.30% (95% confidence interval [CI], 0% to 6.2%). LIMITATIONS: These findings should be validated in larger studies. CONCLUSIONS: Drug-induced thrombocytopenia is a potential side effect of anti-TNF-alpha agents. Immediate monitoring of platelet counts is recommended if autoimmunity is suspected.
Abstract: Papular-purpuric gloves and socks syndrome is a self-limited febrile illness of children and young adults. Only 50 well documented cases have been reported, most of which were associated with parvovirus B19 infection. Molecular detection of the virus from lesional skin has been described in only 5 patients. The syndrome is characterized by a papular-purpuric edematous rash in a distinct "gloves and socks" distribution. Extracutaneous manifestations are usually mild and transient. We report a 42-year-old female with a highly unusual expression of the syndrome, including bullous lesions, lingual aphthae, and conjunctivitis, accompanied by arthritis and a high-grade fever. She had immunoglobulin M and immunoglobulin G antibodies to parvovirus B19, which was detected from lesional skin with the use of polymerase chain reaction for the first time in such a clinical constellation. Because parvovirus B19 infections are generally more severe in adults, we suspect that the unusual disease expression in our patient was related to being more than 40 years of age.
Abstract: BACKGROUND: Palmo-plantar psoriasis (PPP) is a disabling condition that significantly impairs quality of life. PPP tends to be resistant to conventional therapies and may last for several years. Topical treatments are usually ineffective. Systemic therapy with oral retinoids and psoralen plus ultraviolet A is frequently required, although it rarely leads to remission. STUDY DESIGN: We conducted an open-label, pilot study to evaluate treatment of PPP with efalizumab, an anti-CD11a monoclonal antibody approved for the treatment of chronic, refractory moderate to severe plaque psoriasis in adults. METHODS: Five patients with severe PPP received efalizumab treatment for 24 weeks. RESULTS: All five patients responded favourably by week 12 and showed further improvement at week 24 of uninterrupted therapy. Mean physician-assessed severity scores and patient-reported outcome scores improved almost 75% after 12 weeks and 90% after 24 weeks. At week 32, three patients maintained the response seen at week 24, while two patients suspended efalizumab. CONCLUSIONS: Efalizumab therapy was well tolerated and effective in five patients with severe PPP, allowing a significant improvement in quality of life.
Abstract: Radiation therapy, even at low doses, can induce a wide spectrum of vascular skin proliferations ranging from nonmalignant ones, such as benign lymphangiomatous papules (BLAP), to frankly malignant pathologies, such as angiosarcoma. We describe a 50-year-old Caucasian woman with a past history of uterine rhabdomyosarcoma, treated 22 years prior with surgical excision, chemotherapy, and radiotherapy. She presented with a few skin-colored papules and a clear discharge located in the previously irradiated area (right inguinal region). Histopathology showed a proliferation of irregular, interanastomosing vascular channels, thin walled and lined by prominent endothelial cells with focally hobnail features. Cytological atypia of endothelial cells, mitotic figures, hemorrhagic areas, and necrosis were not observed. The endothelial cells expressed D2-40 and CD31. A diagnosis of BLAP following radiotherapy for uterine rhabdomyosarcoma was made. The patient was treated with complete excision using electrodessication. At the 20-month follow-up visit the patient was still free of recurrence.
Abstract: A new resorbable filler, Matridex, became commercially available during the last years with scarce evidence regarding side effects. A 43-year-old woman complained of multiple, painful, reddish, nonulcerated, hard nodules on both cheeks and periocular regions. Four weeks before, she had been injected by a general practitioner with Matridex for aesthetic purposes to correct wrinkles in the same areas of the nodular eruption. Histopathology showed a diffuse suppurative granulomatous reaction with the presence of multinucleate giant cells and many neutrophils involving the entire dermis. No areas of caseation were observed. The inflammatory granulomatous reaction surrounded 2 different types of nonpolarizing, bluish, exogenous material: one arranged in filamentous structures and the second composed by large spherical particles. All nodules were incised and drained; the patient received systemic antibiotic treatment for 2 consecutive weeks. The nodules progressively regressed and almost complete resolution was seen after 6 months. Matridex is a new resorbable filler constituted by a mixture of nonanimal-stabilized hyaluronic acid (HA), cross-linked HA, and dextranomer microspheres. Foreign body reactions have been described in association with other HA fillers, but a granulomatous reaction after the injection of Matridex has not been reported yet. Interestingly, in our patient, we were able to identify both fragments of HA: the filamentous particles and the spherical particles of dextranomer microspheres within the infiltrate, these last giving a characteristic and recognizable appearance to the histopathological picture.
Abstract: BACKGROUND: We tested the relevance of clinical information in the histopathologic evaluation of melanocytic skin neoplasm (MSN). METHODS: Histopathologic specimens from 99 clinically atypical MSN were circulated among ten histopathologists; each case had clinical information available in a database with a five-step procedure (no information; age/sex/location; clinical diagnosis; clinical image; dermoscopic image); each step had a histopathologic diagnosis (D1 through D5); each diagnostic step had a level of diagnostic confidence (LDC) ranging from 1 (no diagnostic certainty) to 5 (absolute diagnostic certainty). The comparison of the LDC was employed with an analysis of variance (ANOVA) for repeated measures. FINDINGS: In D1 (no information), 36/99 cases (36.3%) had unanimous diagnosis; in D5 (full information available), 51/99 cases (51.5%) had unanimous diagnosis (p for difference between proportions <0.001). The observer agreement expressed as kappa increased significantly from D1 to D5. The mean LDC linearly increased for each observer from D1 through D5 (p for linear trend <0.001). On average, each histopathologist changed his initial diagnosis in 7 cases (range: 2-23). Most diagnostic changes were in D2 (age/sex/location). INTERPRETATION: The histopathologic criteria for the diagnosis of MSN can work as such, but the final histopathologic diagnosis is a clinically-aided interpretation. Clinical data sometimes reverse the initial histopathologic evaluation.
Abstract: Brooke-Spiegler syndrome is an autosomal dominant inherited disease with predisposition to cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas. Its onset is in the second or third decades of life. The histopathological exams of the lesions revealed a plethora of benign adnexal neoplasms, showing apocrine, follicular, and sebaceous differentiation. The treatment can be performed by excisional surgery, laser, cryotherapy, electrofulguration and dermabrasion. Due to the risk of malignancy, there is the need for clinical follow-up and genetic counseling.
Abstract: Summary Phaeohyphomycosis is a distinct mycotic infection of the skin or internal organs caused by darkly pigmented (dematiaceous) fungi, which are widely distributed in the environment. Phaeohyphomycosis is most frequently an opportunistic infection in immunosuppressed patients (HIV, corticotherapy, transplant patients) or is frequently associated with chronic diseases and diabetes. The spectrum of the disease is broad and includes superficial infections, onychomycosis, subcutaneous infections, keratitis, allergic disease, pneumonia, brain abscesses and disseminated disease. Rarely, immunocompetent patients may be affected. We describe two new cases of subcutaneous phaeohyphomycosis in immunocompetent patients: in the first patient, the causative agent was Exophiala jeanselmei, a common cause of phaeohyphomycosis; and in the second, Cladophialophora carrionii, which could be identified by culture. Cladophialophora carrionii is mainly the aetiological agent of chromoblastomycosis and only rarely the cause of phaeohyphomycosis. The first patient was treated with surgical excision and oral itraconazole, and the second patient responded to oral itraconazole only. Lesions improved in both patients and no recurrence was observed at follow-up visits.
Abstract: Scleromyxoedema is a rare disease of unknown aetiology that is characterized by progressive cutaneous mucinosis and paraproteinaemia. A variety of systemic (e.g. gastro intestinal, neurological, pulmonary, cardiac and renal) complications may lead to significant morbidity and mortality necessitating therapeutic intervention. The latter remains challenging. Numerous treatment modalities have been reported in the literature, often, however, with inconsistent responses, frequent relapses and potentially serious side-effects. Moreover, the rarity of scleromyxoedema has prevented the execution of controlled therapeutic trials. This paper discusses current proposed therapeutic strategies and reports the case of a 64-year-old male patient with progressive scleromyxoedema associated with IgG-lambda paraproteinaemia in whom monthly administrations of vincristine, idarubicin and dexamethasone in addition to daily oral thalidomide led to clinical and laboratory remission within 12 weeks.
Abstract: Mobile telemedicine integrates wireless communications for different telemedical applications, such as mobile phones and personal digital assistants, and with the implementation of modern wireless telecommunication, wireless local area network and satellite communication is a reality. New generation cellular phones or personal digital assistants have overcome limitations of image quality seen in older devices and, with dermatology being a visual profession, mobile teledermatology is perhaps the most recent development in this field. Mobile teledermatology may provide a triage service aimed toward management of patients with emergent skin disease or for follow-up with patients requiring systemic treatment. Teledermoscopy enables rapid transmission of dermoscopic images via e-mail or specific web-application and studies have demonstrated a high, 91%, concordance between face-to-face diagnosis and remote diagnosis of such images. Further to this, telediagnosis of melanocytic skin neoplasms achieved a diagnostic accuracy of 83% versus the conventional histopathologic diagnosis. Mobile teledermoscopy is the combination of such approaches enabling transfer of images captured with cellular phones coupled with a pocket dermatoscope and preliminary studies have demonstrated the feasibility and potential of its use in triage of pigmented lesions. Such applications are of benefit to physicians in enabling easy storage of data for follow-up or referral of images for expert second opinion and may facilitate a "person-centered health system" for patients with numerous moles and pigmented skin lesions who could forward images for evaluation. The incidence of skin cancers has reached epidemic proportions among whites and the trend is still going upward. Mobile teledermatology and teledermoscopy may be implemented as a triage or screening tool for malignant tumors to facilitate early detection and diagnosis, which is crucial for improved patient outcomes. While the legal aspects concerning teleconsultations need to be evaluated, the communications technologies provide a unique opportunity for physicians and patients alike and we foresee a place for these tools in dermatology soon.
Abstract: BACKGROUND: Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level. OBJECTIVES: To assess cytomorphological and architectural RCM features of facial LM/LMM. METHODS: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. The histopathological diagnosis of LM was made in 15 areas; the other two were diagnosed as early LMM. RESULTS: A focal increase of atypical melanocytes and nests surrounding adnexal openings, sheets of mainly dendritic melanocytes, cord-like rete ridges at the dermoepidermal junction (DEJ) and an infiltration of adnexal structures by atypical melanocytes were found to be characteristic RCM features of facial LM/LMM. Areas with a focal increase of atypical melanocytes and nests surrounding adnexal openings were observed at the basal layer in three cases. The remaining cases displayed these changes at suprabasal layers above sheets of mainly dendritic melanocytes. Cord-like rete ridges at the DEJ and an infiltration of adnexal structures by atypical melanocytes were observed in all cases. Previously described criteria for RCM diagnosis of melanoma, such as epidermal disarray, pleomorphism of melanocytes and pagetoid spreading of atypical melanocytes, were additionally observed. CONCLUSIONS: We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.
Abstract: Trigeminal trophic syndrome is a rare condition resulting from self-manipulation of the skin after a peripheral or central injury to the trigeminal system. The syndrome consists of a classic triad of anesthesia, paresthesias, and secondary persistent or recurrent facial ulcerations. The most common causes include destruction of the trigeminal ganglion, rhizotomy, and stroke. We describe a patient who developed the syndrome as a sequel to brainstem infarction and trigeminal neuropathy. Whereas a-lipoic acid and gabapentin were ineffective, a remarkable benefit was achieved by administering carbamazepine (200 mg 3 times a day), which influences both neuropathic and behavioral factors in this rare syndrome. Our experience with the presented case, together with the scarce information in the literature, indicates that carbamazepine should be the first treatment option for trigeminal trophic syndrome.
Abstract: We investigated the diagnostic agreement between teledermatology based on images from a mobile phone camera and face-to-face (FTF) dermatology. Diagnostic agreement was assessed for two teledermatologists (TD) in comparison with FTF consultations in 58 subjects. In almost three-quarters of the cases (TD1: 71%; TD2: 76%), the telediagnosis was fully concordant with the FTF diagnosis. Furthermore, the diagnosed diseases were almost all in the same diagnostic category (TD1: 97%; TD2: 90%). If mobile teledermatology had been used for remote triage, TD1 could have treated 53% subjects remotely and 47% subjects would have had to consult a dermatologist FTF. TD2 could have treated 59% subjects remotely, whereas 41% subjects would have had to consult a dermatologist FTF. Forty-eight subjects responded to a questionnaire, of whom only 10 had any concerns regarding teledermatology. Thirty-one subjects stated that they would be willing to pay to use a similar service in future and suggested an amount ranging from euro5 to euro50 per consultation (mean euro22) (euro = pound0.7, US $1.4). These results are encouraging as patient acceptance and reimbursement represent potential obstacles to the implementation of telemedicine services.
Abstract: Most cases of intravascular large cell lymphoma have a B-cell phenotype, but rare T-cell and natural killer (NK)-cell variants have been reported. We describe the clinicopathologic features of 4 patients (M:F=3:1; age range: 63 to 87; median age: 65) with intravascular large NK/T-cell lymphoma. The skin was the site of presentation in all patients (leg: 1 case; trunk: 1 case; trunk and extremities: 2 cases). Two patients had lesions confined to the skin; in 1 case concomitant involvement of the brain was detected and in 1 case no further studies were carried out. Immunohistology showed positivity for cytotoxic markers in 3/4 cases. One case had an NK phenotype similar to NK/T-cell lymphoma, nasal-type, whereas the other cases could not be precisely classified into specific categories (peripheral T-cell lymphoma, NOS). One of these cases was negative for cytotoxic markers and was positive only for CD2 and CD3 epsilon. Association with Epstein-Barr virus (EBV) was demonstrated in 2 cases by in situ hybridization, whereas 1 case was negative. All our patients had aggressive disease and died between 2 weeks and 7 months from presentation. Analysis of our cases and of those published in the literature shows that intravascular large NK/T-cell lymphoma is a rare, aggressive lymphoma with variable phenotypic features, frequent expression of cytotoxic proteins, true NK-cell phenotype and association with Epstein-Barr virus infection, and common presentation in the skin. Homogeneous studies on larger number of patients and reevaluation of cases published with incomplete phenotypic data would be necessary to gather more information on this extremely rare type of lymphoma.
Abstract: In the WHO classification, subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a distinct type of T-cell lymphoma with an aggressive clinical behavior. Recent studies suggest that distinction should be made between SPTL with an alpha/beta T-cell phenotype (SPTL-AB) and SPTL with a gammadelta T-cell phenotype (SPTL-GD), but studies are limited. To better define their clinicopathologic features, immunophenotype, treatment, and survival, 63 SPTL-ABs and 20 SPTL-GDs were studied at a workshop of the EORTC Cutaneous Lymphoma Group. SPTL-ABs were generally confined to the subcutis, had a CD4-, CD8+, CD56-, betaF1+ phenotype, were uncommonly associated with a hemophagocytic syndrome (HPS; 17%), and had a favorable prognosis (5-year overall survival [OS]: 82%). SPTL-AB patients without HPS had a significantly better survival than patients with HPS (5-year OS: 91% vs 46%; P<.001). SPTL-GDs often showed (epi)dermal involvement and/or ulceration, a CD4-, CD8-, CD56+/-, betaF1- T-cell phenotype, and poor prognosis (5-year OS: 11%), irrespective of the presence of HPS or type of treatment. These results indicate that SPTL-AB and SPTL-GD are distinct entities, and justify that the term SPTL should further be used only for SPTL-AB. SPTL-ABs without associated HPS have an excellent prognosis, and multiagent chemotherapy as first choice of treatment should be questioned.
Abstract: Ancient melanocytic nevi are benign melanocytic neoplasms that show degenerative and atypical changes, sometimes leading to a misdiagnosis of melanoma. We describe 6 patients (M:F ratio 4:2; age range, 15-84 years; median, 50 years) who presented with cellular blue nevi showing stromal changes resembling those of ancient melanocytic nevi. The lesions were located on the buttocks (4 patients) and on the trunk (2 patients) and clinically consisted of heavily pigmented nodules. Histology revealed the architectural pattern of cellular blue nevi. However, the architecture was strikingly altered by stromal changes like those seen in ancient melanocytic nevi, including increased number of large, dilated vessels with pseudoangiomatous features in 4 cases, hyaline angiopathy in 4 cases, myxoid changes, sclerosis or hyalinization of the stroma in all cases, and variable amounts of edema in 4 cases. In 2 cases, a large edematous area was present in the center of the lesion, and nests of ovoidal melanocytes and single dendritic melanocytes appeared to "float" in the stroma. Pleomorphic melanocytes were observed in all cases. Ancient blue nevi represent a morphologic variation of cellular blue nevi-Masson neuronevi with degenerative stromal changes. Recognition of these lesions can help prevent overdiagnosis of melanoma.
Abstract: BACKGROUND: A systematic examination and comparison of confocal scanning laser microscopy (CSLM) features of benign naevi showing different dermoscopic patterns has never been performed. OBJECTIVES: Systematically to assess CSLM features of dermoscopically benign reticular, globular and homogeneous naevi and to correlate CSLM findings with dermoscopy and histopathology. METHODS: CSLM was performed on 30 naevi in 29 patients including 10 reticular, 10 globular and 10 homogeneous naevi showing a uniform pigmentation pattern with dermoscopy. Cytomorphological and architectural features of each naevus were assessed and distinct characteristics for each group of naevi were defined. CSLM features were correlated with the histopathological findings and their applicability for the diagnosis of naevi with different dermoscopic patterns was assessed by two blinded observers. RESULTS: A correct diagnosis was made in 26 and 28 of 30 cases, respectively, by two blinded observers using previously defined CSLM features. Well-defined melanocytic caps, well-defined edged papillae and black papillae concurrently with the absence of white papillae were found in all reticular naevi (10 of 10). Numerous, large junctional/dermal melanocytic nests (10 of 10), ill-defined edged papillae (eight of 10) and white papillae (nine of 10) were found in globular naevi. Homogeneous naevi showed an intermediate pattern between reticular and globular naevi: ill-defined edged papillae (10 of 10), black and white papillae within the same naevus (eight of 10) and junctional/dermal melanocytic nests (three of 10) were seen. CONCLUSIONS: Different dermoscopic patterns of benign naevi are reflected in different architectural features in CSLM. As benign naevi show a regular architecture of monomorphous melanocytes in contrast to melanomas, similar dermoscopic features of naevi and early melanomas may be differentiated by CSLM.
Abstract: BACKGROUND: Primary cutaneous anaplastic large T-cell lymphoma (PCALCL) is a well-defined entity with prognostic differences from the nodal counterpart [nodal anaplastic large cell lymphoma (NALCL)]. Several histological variants of NALCL have been characterized (common, lymphohistiocytic and small cell). However, studies on morphological variants of PCALCLs are lacking. METHODS: We analyzed retrospectively the clinicopathologic features of 66 biopsies from 47 patients (M : F = 27 : 20; median age: 53 years; mean age: 51.8 years; range: 14-82) with PCALCL, in order to better characterize the spectrum of this unusual neoplasm. RESULTS: The 'common variant' was the most frequent (40.4%). In contrast to NALCL, in PCALCL, marked reactive infiltrates are more commonly present. In fact, 26 cases were classified as 'inflammatory type' (15 cases) and 'lymphohistiocytic' (11 cases). Concerning the predominant cell morphology, large anaplastic cells (33%) were almost as frequent as large pleomorphic (36%) and small to medium-sized cells (26%). We reported for the first time in the skin 2 rare cases with the predominance of large cells with a 'signet-ring'-like appearance. Epidermotropism and presence of eosinophils were found in a proportion of cases in all PCALCL variants. CONCLUSIONS: PCALCL is characterized by variable histopathological presentations and a broad cytomorphologic spectrum.
Abstract: BACKGROUND: The influence of phenotype and detection of clonality on prognosis in early mycosis fungoides has never been addressed in large studies. OBJECTIVES: To correlate immunophenotype and detection of clonality with clinical outcome. METHODS: We analysed 73 biopsy specimens from 68 patients with early mycosis fungoides (stage Ia or Ib) and at least 10 years of follow up (or dead of disease). RESULTS: Four phenotypic groups could be identified: group A (alpha/beta+ CD4+ CD8- TIA1-), 51 patients; median survival time 160 months; group B (alpha/beta+ CD4- CD8+ TIA1+), 10 patients; median survival time 195 months; group C (alpha/beta- CD4- CD8+/- TIA1+), five patients; median survival time 165 months; and group D (alpha/beta+ CD4- CD8- TIA1-), two patients; median survival time 130 months. Survival curves did not show statistical differences among the groups. Monoclonality was detected in 36 of 67 tested biopsies (54%), and statistical analyses did not show prognostic differences between the clonal and nonclonal cases. CONCLUSIONS: We conclude that cytotoxic phenotype and detection of monoclonal T-cell receptor-gamma gene rearrangement in early lesions of mycosis fungoides do not have any prognostic significance.
Abstract: Dermatology is perhaps the most visual specialty in medicine, making it ideally suited for modern telemedicine techniques, as has been shown in a number of recent studies investigating feasibility and reliability of teledermatology. It has generally demonstrated high levels of concordance in diagnosis and management plans compared with face-to-face consultations. Teledermatology has been also used for various purposes, including triage, diagnostic and management services, and second opinion services for primary care practitioners. It has been set up in a number of ways: 1) direct referral for primary care using images and clinical history sent to secondary care dermatology services for second opinion and for triage referrals; and 2) facilitating community-based clinics led by nurses or general practitioners. Moreover, in the last years new fields in teledermatology have grown up. Teledermoscopy is a promising area for melanoma screening as well as for diagnosis and management of equivocal pigmented skin lesions. The feasibility of mobile teledermatology and mobile teledermoscopy has been recently proved and these new facilities have the potential to become an easy applicable tool for everyone and may open the door for a new flexible triage system for detection of skin cancer in general and melanoma in particular. The implementation of virtual slide systems for teledermatopathology has allowed avoiding the limitations imposed by conventional photographs. Finally, web consultations in dermatology are a rather new tool that became available in the last years and teledermatologic services through the Internet offer many possibilities, including continuing medical education, on-line atlases and databases, and specific web application suited for teledermatology (i.e. www.telederm.org).
Abstract: Dermatology is perhaps the most visual specialty in medicine, making it ideally suited for modern telemedicine techniques, as has been shown in a number of recent studies investigating feasibility and reliability of teledermatology. It has generally demonstrated high levels of concordance in diagnosis and management plans compared with face-to-face consultations. Teledermatology also has been used for various purposes, including triage, diagnostic and management services, and second-opinion services for primary care practitioners. It has been set up in a number of ways: (1) direct referral for primary care using images and clinical history sent to secondary care dermatology services for second opinion and for triage referrals and (2) facilitating community-based clinics led by nurses or general practitioners. Moreover, in the last years new fields in teledermatology have grown up. Teledermoscopy is a promising area for melanoma screening as well as for the diagnosis and management of equivocal pigmented skin lesions. The feasibility of mobile teledermatology and mobile teledermoscopy recently has been proven, and these new facilities have the potential to become an easy applicable tool for everyone and may open the door for a new flexible triage system for detection of skin cancer in general and melanoma in particular. The implementation of virtual slide systems for teledermatopathology has allowed avoiding the limitations imposed by conventional microphotography. Finally, web consultations in dermatology are a rather new tool that became available in the last years and teledermatologic services through the Internet offer many possibilities, including continuing medical education, on-line atlases and databases, and specific web application suited for teledermatology (ie, www.telederm.org).
Abstract: Teledermatopathology may involve real-time transmission of images from distant locations to consulting pathologists by the remote manipulation of a robotic microscope. Alternatively, the static store-and-forward option involves the single-file transmission of subjectively preselected and captured areas of microscopic images by a referring physician. The recent introduction of virtual slide systems (VSS) involves the digitization of whole slides at high resolution thus enabling the user to view any part of the specimen at any magnification. Such technology has surmounted previous restrictions caused by the size of preselected areas and specimen sampling for telepathology. In terms of client access, these VSS may be stored on a virtual slide server, made available on the Web for remote consultation by pathologists via an integrated virtual slide client network. Despite store-and-forward teledermatopathology being the most frequently used and less expensive approach to teledermatopathology, VSS represents the future in this discipline. The recent pilot studies suggest that the use of remote expert consultants in diagnostic dermatopathology can be integrated into daily routine, teleconsultation, and teleteaching. The new technology enables rapid and reproducible diagnoses, but despite its usability, VSS is not completely feasible for teledermatopathology of inflammatory skin diseases as the performance seems to be influenced by the availability of complete clinical data. Improvements in the diagnostic facility will no doubt follow from further development of the VSS, the slide processor, and of course training in the use of virtual microscope. Undoubtedly, as technology becomes even more sophisticated in the future, VSS will overcome the present drawbacks and find its place in all facets of teledermatopathology.
Abstract: BACKGROUND: CD4+/CD56+ hematodermic neoplasm (HN) (blastic natural killer (NK)-cell lymphoma) is a rare entity characterized by dense, monomorphous infiltrates of medium-sized cells with blastic appearance and a characteristic immunophenotype (positivity for CD4, CD56 and CD123). The combination of CD4 and CD56 positivity is thought to be so striking that it has been used to name this entity. METHODS: Three cases of HN with ambiguous phenotypic profile were included in this study. In all cases, phenotypic, molecular and in situ hybridization studies were carried out. RESULTS: All three cases showed an aberrant phenotype with negativity for CD4. CONCLUSIONS: CD4-negative or CD56-negative cases of HN have been rarely reported in the literature and represent a diagnostic problem. Our three cases confirm that CD4 is not always expressed in these neoplasms. The term 'CD4+/CD56+ hematodermic neoplasm' adopted in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas may be misleading and should probably be revised in the light of all data published in the literature.
Abstract: BACKGROUND: Cutaneous infectious and inflammatory diseases may contain a significant number of CD30-positive cells, thus mimicking lymphomatoid papulosis (LyP) or anaplastic large cell lymphoma. METHODS: We reviewed our cases of non-neoplastic skin conditions with large, CD30-positive cells and searched the literature for similar cases. RESULTS: A total of 28 cases were included in the study: Milker's nodule (n = 8), Herpes simplex virus infection (n = 7), lymphomatoid drug reaction (n = 3), molluscum contagiosum (n = 3), nodular scabies (n = 2), leishmaniasis (n = 1), syphilis (n = 1), pernio (n = 1), ruptured infundibular cyst (n = 1) and pseudolymphoma in a scar (n = 1). CD30-positive cells were often arranged in clusters and revealed both Golgi and membrane positivity, similar to what was observed in LyP and CD30+ anaplastic large T-cell lymphoma. CONCLUSIONS: Analysis of our data and of those published in the literature shows that viruses and drugs are the most common cause for occurrence of large CD30-positive cells in cutaneous pseudolymphomatous infiltrates. Arrangement of these large, CD30-positive cells in small clusters is not unique to cutaneous CD30-positive lymphomas, and in many cases a precise diagnosis can be made only upon accurate clinicopathological correlation or using ancillary methods such as polymerase chain reaction analysis for viral DNA.
Abstract: BACKGROUND: The dermoscopic diagnosis of cutaneous melanoma (CM) may be difficult because some CM lack specific dermoscopic features for melanoma diagnosis. OBJECTIVE: To evaluate whether a diagnosis of CM could be achieved using the classic dermoscopic melanoma-specific criteria, we conducted a retrospective multicenter study of 508 CM samples. METHODS: All the dermoscopic images were analyzed to identify the dermoscopic criteria found in dermoscopically difficult melanomas (DDM) and to examine the possible relation of dermoscopic diagnosis with respect to the difficulty of the dermoscopic diagnosis and the melanoma thickness. RESULTS: A significant percentage of melanomas, 89 of 508 (17.5%), were DDM. The criteria leading to a significant increased risk of DDM were presence of streaks [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.15-4.47), absence or presence of regular pigmentation (OR, 3.41; 95% CI, 1.70-6.85), absence of a blue-whitish veil (OR, 4.04; 95% CI, 2.33-6.99), absence of regression structures (OR, 4.31; 95% CI, 2.42-7.66), and the presence of hypopigmentation (OR, 2.61; 95% CI, 1.49-4.58). CONCLUSION: A significant number of melanomas defy even dermoscopic diagnosis. Only a meticulous comparative and interactive process based on an assessment of all the individual's other nevi ("ugly ducking" sign) and a knowledge about recent changes can lead to the recognition of DDM.
Abstract: BACKGROUND: Telemedicine is the practice of healthcare using interactive processes of communication to facilitate healthcare delivery, including diagnosis, consultation and treatment, as well as education and transfer of medical data. The aim of teledermatology, just as telemedicine, is to promote best practice procedures and to improve the consistency and competence of health care. AIM: To investigate the diagnostic additive value of second opinion teleconsulting in patients with challenging dermatoses, among dermatologists working in two different dermatology departments. SETTING: Thirty-three cases of patients with challenging inflammatory and neoplastic skin diseases at the University of L'Aquila Department of Dermatology were sent for teleconsultation to the Department of Dermatology, Medical University of Graz, Austria. METHODS: All cases were selected in the outpatient service in L'Aquila. After face-to-face consultation with a local colleague had been completed, images were sent using a store-and-forward (SAF)-based system (http://www.telederm.org) to Graz. Histopathological examination together with follow-up of the patient represents the diagnostic gold standard for this study. RESULTS: Telediagnosis was correct in 26 of 33 (78.8%) cases. Sixteen of 33 cases (48.5%) had already been diagnosed face-to-face by at least one of the two dermatologists in L'Aquila. In 10 of 33 cases (30.3%), the correct diagnosis was made in teleconsultation only. CONCLUSIONS: Second opinion teleconsulting may represent an additive value in the diagnosis of numerous challenging inflammatory and neoplastic skin diseases. It may be particularly useful as a best practice model for smaller departments in order to discuss and/or to confirm diagnoses and also for the management of patients with unusual difficult dermatoses.
Abstract: BACKGROUND: Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. METHODS: A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. RESULTS: Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal-type extranodal natural killer/T-cell lymphoma; and (4) "classical" cases of cutaneous T-cell lymphoma (CTCL) with co-expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2-72 months), whereas all patients with CD56+ CTCL were alive at the last follow-up. CONCLUSION: Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders.
Abstract: BACKGROUND/PURPOSE: Polymorphic light eruption (PLE) is a common photodermatosis of potential autoimmune origin, and an overlap with lupus erythematosus (LE) has been described. Plasmacytoid dendritic cell (PDC)-induced expression of interferon (IFN)-alpha has been found to be present in LE skin lesions and plays a pivotal role in the pathogenesis of LE by promoting autoimmunity. We therefore asked whether PDCs may also be involved in the pathogenesis of PLE and searched for those cells [which can be identified by their high levels of interleukin (IL)-3 receptor alpha chain (CD123), combined with other cell markers such as CD68] in skin lesions. METHODS: Paraffin-embedded biopsy specimens from a total of 27 patients with clinically and histologically confirmed PLE (nine women, mean age 32.7 years, age range 18-43), LE (seven women, four men, CCLE: n=4, SCLE: n=2, lupus tumidus: n=5, mean age 48.5 years, age range 41-65) or psoriasis (four women, three men, mean age 43.3 years, age range 19-54) (as control group) were analyzed by immunohistochemical CD68/CD123 double staining. Quantification of the immunohistochemical staining was performed by visual cell counting of CD68-/CD123+, CD68+/123-, and CD68+/CD123+ cells separately in the epidermis and dermis of the samples in at least 10 random fields per sample at x 400 microscopic magnification by two of the investigators in a blinded fashion. RESULTS: Microscopic examination of the immunohistochemically stained sections revealed that CD68+/CD123+ cells were present in most specimens obtained from LE [10/11 (91%)] and psoriasis [6/7 (86%)] patients but not at all in those obtained from PLE patients. Quantification and statistical analysis of the dermal infiltrate revealed that CD68+/CD123+ cells were present at a mean+/-SEM field density of 5.6+/-1.3 in LE, 1.6+/-0.6 in psoriasis but totally absent in PLE (P=0.0010 vs. LE, P=0.0135 vs. psoriasis by an unpaired Student's t-test). CONCLUSION: The results confirm the potential significance of PDCs in LE and psoriasis, however the absence of PDCs in PLE contradicts the hypothesis that these cells might play a role in the latter disease.
Abstract: BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria). Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp) where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.
Abstract: We investigated the feasibility and diagnostic agreement of a virtual slide system (VSS) in teledermatopathology. Forty-six biopsy specimens from inflammatory skin diseases were selected and scanned with a VSS at the Research Unit of Teledermatology, Medical University of Graz, Graz, Austria. Images were stored on a virtual slide server on which a specific Web application suited for telepathology (http://telederm.org/research/dermatopath/) runs. Twelve teleconsultants from 6 different countries reviewed the 46 cases, working directly on the Web application. Telediagnoses agreed with gold standard and conventional diagnosis with an average of 73% and 74%, respectively. Complete concordance among all teleconsultants with gold standard and conventional diagnosis was found in 20% of the cases. In 10 cases in which complete clinical data were missing, the average agreement of telediagnosis with gold standard diagnosis and conventional diagnosis decreased to 65% and 66%, respectively. Only 3 of 4 cases of inflammatory skin diseases were correctly diagnosed remotely with VSS. The system that we have used, despite its usability, is not completely feasible for teledermatopathology of inflammatory skin disease. Moreover, the performance seems to have been influenced by the availability of complete clinical data and by the intrinsic difficulty of the pathology of inflammatory skin diseases.
Abstract: Pseudolymphomas are a rare complication of vaccination, presenting with dense lymphoid infiltrates and prominent follicular pattern. We report our observations on 4 patients with vaccination-induced B-cell pseudolymphoma (all females; age range 19 to 60 years; median: 34.5 years). Clinically 3 patients presented with subcutaneous nodules and 1 presented with a large, indurated, erythematous plaque. Histology revealed in all cases dense lymphoid infiltrates in the subcutaneous fat with prominent follicular pattern. The follicles displayed features of reactive germinal centers (normal mantle zone, presence of tingible body macrophages, normal proliferation). Necrotic areas surrounded by palisaded histiocytes were seen in 3 biopsies from 2 patients. A mixed-cell infiltrate with eosinophils and plasma cells was present in all cases. In addition, histiocytes with granular basophilic cytoplasm could be observed around the focal area of necrosis or within the inflammatory infiltrate. Follow-up was available for 3 patients. One patient was alive with persistent disease 6 months after the first observation. Two patients were treated with local radiotherapy and are alive and free of disease after 12 and 72 months, respectively. One of these two patients had a second pseudolymphoma on the contralateral arm after a new injection of vaccine. Cutaneous pseudolymphoma after vaccination should be distinguished histopathologically from low-grade cutaneous B-cell lymphomas (follicle center cell lymphoma, marginal zone lymphoma) and from other B-cell pseudolymphomas with prominent follicular pattern requiring different treatment (eg, Borrelia burgdorferi-induced lymphocytoma cutis).
Abstract: BACKGROUND: Antibodies to stratified epithelia characterize chronic ulcerative stomatitis, an entity that very closely resembles erosive lichen planus both clinically and histologically. These antibodies are directed against a 70-kd antigen. OBJECTIVE: Our aim was to verify whether antibodies to stratified epithelia are present in patients with common lichen planus. PATIENTS AND METHODS: One hundred thirty-eight patients with various forms of lichen planus were studied. Indirect immunofluorescence was performed on both monkey esophagus and HEp2-2000 cells. Immunoblotting was done with cultured keratinocytes used as the source antigen. RESULTS: Nineteen patients had antibodies to stratified epithelia (in 9 directed against an antigen of 70 kd). Forty-eight patients had circulating antibodies detected by indirect immunofluorescence on both monkey esophagus and HEp2-2000 cells (in 7 directed against an antigen of 70 kd). Indirect immunofluorescence was positive only on HEp2-2000 cells in 21 patients. Indirect immunofluorescence was negative in 50 patients on both HEp2-2000 cells and monkey esophagus. None of the last 71 patients had antibodies directed to an antigen of 70 kd. LIMITATIONS: This is a serological study; results from direct immunofluorescence studies would be interesting. CONCLUSION: Antibodies to stratified epithelia directed to an antigen of 70 kd are not exclusive to chronic ulcerative stomatitis, but are also present in some patients with lichen planus.
Abstract: A 52-year-old man was examined for an ulcerated, rapidly growing reddish nodule. It was 5.5 cm high with an 11 x 6-cm base and located on the left clavicle. The lesion had been present for approximately 7 years, and the patient complained occasional burning and pain. Clinical differential diagnoses included cutaneous lymphoma, sarcoma, squamous cell carcinoma, and cutaneous metastasis. Histopathologic examination revealed a well-circumscribed tumor involving the whole dermis and the subcutis and composed of partially confluent aggregates of matrical cells admixed with eosinophilic cornified material containing shadow cells. In addition, multinucleated giant cells, areas of calcification and metaplastic ossification, edema, and hemorrhage were also observed. On the basis of histopathologic features, the diagnosis of pilomatricoma was made. Our report highlights an unusual clinical appearance of pilomatricoma that made us consider a variety of primary or secondary cutaneous neoplasms in its differential diagnosis.
Abstract: A non-commercial teledermatology network based on store-and-forward operation was established in April 2002. The aim was to create an easy-to-use platform for teleconsultation services, where physicians could seek diagnostic advice in dermatology from a pool of expert consultants and where they could present and discuss challenging dermatology cases with special emphasis on diagnosis and therapy. An online moderated discussion forum was added in October 2003. During the first two years, 348 health-care professionals from 45 countries registered to use the Website. A total of 783 requests for consultations were answered; 285 requests concerned pigmented skin lesions, 440 requests were from the whole range of clinical dermatology and 58 requests were about non-melanoma skin cancer. Of a total of 133 requests analysed, 80 (60%) were answered within one day, 47 (35%) within one week, five (4%) within two weeks and one (1%) consultation was answered in more than two weeks. Our experience with a discretionary, non-commercial, multilingual Website for open-access teleconsulting in dermatology appears to be successful. The Website represents an example of user-generated content, together with active interaction between users, who can present and discuss cases with remote colleagues.
Abstract: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features. Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.
Abstract: BACKGROUND: Melanocytic nevi with eccentric foci of hyperpigmentation ("Bolognia sign") can be considered as a melanoma-simulating type of acquired melanocytic nevus. We report on the morphologic changes of this type of melanocytic nevus over a 39-month period of dermoscopic follow-up. OBSERVATIONS: A 5-year-old girl had a 4-mm brown papule with a peripheral blue-black area on her right upper arm. The eccentric focus of the hyperpigmentation corresponded dermoscopically to a blue-gray area of pigmentation associated with irregular brown-black globules or dots and partially with a superficial black network. After 39 months, a globular type of acquired melanocytic nevus was detectable, which clinically and dermoscopically appeared to be completely benign. A nearly identical situation was observed in 5 other melanocytic nevi, underlining the involution of the pigmented foci in these nevi. The histopathologic diagnoses of 2 lesions were consistent with a compound type of acquired melanocytic nevus with eccentric foci of hyperpigmentation. CONCLUSIONS: Dermoscopy allows identification of a morphologic pathway of modifications, probably typical for this type of melanocytic nevus in children, and therefore enables avoidance of surgical excision with attendant hypertrophic scarring in children. Conversely, in adults, when dermoscopic follow-up of melanocytic nevi reveals eccentric foci of hyperpigmentation, surgical excision of the lesion is indicated.
Abstract: BACKGROUND: Subcutaneous T-cell lymphoma (STCL) represents a controversial entity and a confused concept in the field of cutaneous T-cell lymphomas (CTCLs). Recently, alpha/beta+/CD8+ STCL has been recognized by the new World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphomas as a distinct entity in the group of CTCLs. OBSERVATIONS: We reviewed a series of 53 biopsies from 26 patients (F : M = 19:7; median age: 48; range 18-87) of cutaneous B- and T-cell lymphomas characterized by prominent involvement of the subcutaneous tissue. We could classify our cases according to the following seven categories--(i) STCL: n = 16; (ii) extranodal NK/T-cell lymphoma, nasal type: n = 2; (iii) cutaneous gamma/delta T-cell lymphoma: n = 2; (iv) anaplastic CD30+ large T-cell lymphoma: n = 1; (v) diffuse large B-cell lymphoma, secondary cutaneous: n = 3; (vi) lymphoplasmacytic lymphoma, secondary cutaneous: n = 1; (vii) specific cutaneous manifestations of myelogenous leukemia: n = 1. CONCLUSIONS: We demonstrated the protean nature of lymphomas with prominent involvement of the subcutaneous fat tissues. The term STCL should be restricted to a homogeneous group of cases characterized morphologically by an exclusive involvement of subcutaneous tissues, immunohistochemically by a T-cytotoxic alpha/beta phenotype, and biologically by a relatively good prognosis.
Abstract: Pseudoporphyria is a blistering disease with skin fragility and shallow scarring that clinically and histopathologically closely resembles porphyria cutanea tarda. The two conditions can be distinguished by porphyrin levels that typically are elevated in porphyria cutanea tarda, but not or only slightly in pseudoporphyria. Pseudoporphyria can be induced by various medications (e.g. non-steroidal anti-inflammatory drugs, antibiotics, diuretics, retinoids), intense UV(A) exposure, or haemodialysis. Treatment of haemodialysis-associated pseudoporphyria is not yet standardized. We report here a 65-year-old male patient with chronic renal failure due to Waldenström's macroglobulinaemia who was treated with conventional 3 times/week haemodialysis. He developed blistering skin changes on both hands, which were diagnosed as pseudoporphyria based on clinical, histopathological, and laboratory findings, and could be successfully managed with initial oral N-acetylcysteine and a switch from low-flux to high-flux membrane haemodialysis. The beneficial effect of the high-flux membrane technique in haemodialysis-associated pseudoporphyria has not been previously reported.
Abstract: BACKGROUND: Clark nevi (atypical melanocytic nevi) can be considered as risk markers and potential precursors of melanoma. The authors report on the morphologic changes of an atypical nevus by dermoscopic follow-up examination over a 7-year period. CASE REPORT: A 43-year-old man had a brown macule on his back, sized 5 mm, with an irregular shape, clinically and dermoscopically diagnosed as an equivocal melanocytic lesion. Dermoscopically during the initial examination, a predominant reticular pattern with peripheral eccentric hyperpigmentation in the lower portion of the lesion could be seen. After 7 months, the area of peripheral eccentric hyperpigmentation had regressed, and after 4.5 years the atypical pigment network had almost disappeared. After 7 years of follow-up, a diffuse area of hypopigmentation and a residual light brown pigmentation were detectable. The histopathologic diagnosis was consistent with an atypical junctional nevus with regression with features of a Clark nevus. CONCLUSION: Based on our observation, even a dermoscopically atypical nevus may undergo regression as documented by long-term dermoscopic follow-up.
Abstract: Telepathology is the practice of diagnostic histopathology performed on digital pictures. In this study, we focused on the technical requirements for achievement of a correct diagnosis on digital histopathologic images. A collection of 560 melanocytic lesions was selected from the files of the Department of Dermatology, Medical University of Graz, Austria. From each lesion one histologic slide was completely digitally scanned with a robotic microscope. Digital pictures were reviewed by 4 dermatopathologists using a presentation program, which recorded the number of image calls, applied magnifications, overall time needed, and amount of transmitted bits during the digital sign-out. One month later, the 4 microscopists had to review the corresponding slides and render a direct diagnosis on each case. Telepathologic diagnoses corresponded with the original diagnoses in a range from 90.4% to 96.4% of cases (kappa 0.80 to 0.93; P < 0.001). The median time needed for achievement of a diagnosis was 22 seconds and was significantly higher for melanomas compared with nevi. The median transmission effort for each diagnosis was 510 kilobytes after JPEG compression. Using an ISDN line with a transmission capacity of 64 kilobits/ second, this correlates to a transmission time of about 1 minute. Our results demonstrate that correct reporting on digital histopathologic images is possible with only a little time exposure. For an adequately fast transmission ISDN lines are suffcient after JPEG compression.
Abstract: In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the examination of skin morphology in real time at a resolution equal to that of conventional microscopes. The aim of the study was to test the applicability of CLSM to the diagnostic discrimination of benign nevi and melanoma. five independent observers without previous experience in CLSM received a standardized instruction about diagnostic CLSM features. Subsequently, 117 melanocytic skin tumors (90 benign nevi and 27 melanoma), imaged using a commercially available, near-infrared, reflectance confocal laser scanning microscope, were evaluated by each observer. Overall, sensitivity of 88.15% and specificity of 97.60% was achieved by the five observers. Logistic regression analysis revealed that mainly cytomorphology, architecture and keratinocyte cell borders should be taken into account for diagnostic decisions. Remarkably, using the presence or absence of monomorphic melanocytes as a single diagnostic criterion, the classification results with a sensitivity of 98.15% and a specificity of 98.89% were superior to the intuitive, integrative judgement of the observers. This first sensitivity and specificity study with CLSM has yielded promising results. CLSM provides new and useful information to the clinician diagnosing melanocytic skin tumors.
Abstract: The histologic diagnosis of early mycosis fungoides (MF) is one of the most vexing problems in dermatopathology. We reviewed the histopathologic features of 745 biopsy specimens from 427 patients (male:female = 277:150; median age, 52 years; range, 3-95 years) with early (patch) lesions of MF collected from the lymphoma database of the Department of Dermatology of the Medical University of Graz (Austria). In all patients, the diagnosis was established by clinicopathologic correlation. The most common histopathologic pattern consisted of a band-like or patchy lichenoid infiltrate admixed with coarse bundles of collagen in the superficial dermis. Epidermotropism of lymphocytes was observed in most cases in one or more forms (single lymphocyte epidermotropism, 22%; basilar lymphocytes, 23%; Pautrier's microabscesses, 19%; "haloed" lymphocytes, 40%; disproportionate exocytosis, 17%; pagetoid epidermotropism, 3%). In 4% of cases, epidermotropism was completely missing. Atypical lymphocytes were present only in 9% of cases. Features of interface dermatitis were observed in 59% of cases. Other unusual findings were the presence of necrotic keratinocytes (23%), melanophages (8%), and extravasated erythrocytes (4%). In 28 patients, two or more biopsies taken on the same day at different body sites showed different histopathologic aspects, underlying the protean features of MF even in a single patient at a given time. Our study expands previous observations on histopathologic features of early lesions of MF. Although sometimes the histopathologic features are not diagnostic, they should be considered consistent with MF and do not rule out the diagnosis.
Abstract: BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. In early stages of the disease many different clinicopathologic variants have been observed. OBSERVATION: We report 6 patients with early manifestations of MF characterized by the sole presence of papules which, unlike the papules of lymphomatoid papulosis, did not show a tendency for spontaneous resolution. Histologic examination confirmed the diagnosis of MF in all cases. Immunohistochemical staining for CD30 was negative in all cases. Follow-up data showed the nonaggressive behavior of the disease, confirming that the lesions were not manifestations of advanced MF. CONCLUSION: Papular MF is a new variant of early MF characterized by the presence of papules in the absence of more conventional early lesions (patches) of the disease. This variant should be added to the long list of clinicopathologic subtypes of MF.
Abstract: Lennert's lymphoma (LL) is a T-cell lymphoma characterized by the presence of atypical T lymphocytes, admixed with histiocytes and epithelioid granulomas. Patients present with superficial lymph node involvement, mainly in the cervical areas; thoracic adenopathies and involvement of deep abdominal lymph nodes are rare. Cutaneous involvement is infrequent, reported to occur in only 4-11% of patients, and even rarer is the onset of cutaneous lesions as first sign of a recurrence. We report a female patient who presented with papules and nodules on the trunk and upper limbs as the first manifestation of recurrent LL.
Abstract: PURPOSE OF REVIEW: The worldwide incidence of melanoma and nonmelanoma skin cancers is increasing alarmingly. The development of new techniques such as dermoscopy leads to a consequent progress in skin cancers screening. The purpose of this review is to highlight recent advances in dermoscopy, reviewing primary research articles published in the last year. RECENT FINDINGS: With the recent standardization of diagnostic procedures obtained by the Consensus Net Meeting on Dermoscopy and the definition of new melanoma-specific criteria, the efficacy in early melanoma diagnosis is improved. Dermoscopy is cost effective, leading to a decreased number of excised benign lesions, and the dermoscopic follow-up allows early detection of melanomas. However, the technique must be performed by experts in order not to miss melanomas. For this reason, instruction in dermoscopy is mandatory. Moreover, computer-aided diagnosis has been tested to be a valid support for physicians. Teledermoscopy is a new tool that allows a second expert opinion to manage atypical lesions. SUMMARY: Dermoscopy opens up a new dimension on clinical morphology of skin lesions. Digital follow-up examinations, computer-aided diagnosis, and teledermoscopy are new facilities that will change the current management of skin cancers in general and melanoma in particular. Dermoscopy in the hands of experienced physicians has higher discriminatory power than naked-eye examination to detect skin cancers.
Abstract: OBJECTIVE: To evaluate the diagnostic accuracy of confocal examination of basal cell carcinoma (BCC) in microscopy-guided surgery. DESIGN: Four independent observers with no previous experience in confocal laser scanning (CLS) microscopy received standardized instruction about diagnostic CLS microscopic features. Subsequently, 120 confocal images of fresh excisions from BCCs or normal skin were evaluated by each observer, imaged using a commercially available, near-infrared, reflectance CLS microscope. Logistic regression analysis was performed on a combination of all morphologic features using the forward-stepwise (Wald) method. Reliability (interobserver agreement) data were evaluated by kappa statistic. SETTING: Department of Dermatology, Medical University of Graz. PATIENTS: Twenty patients with histologically verified BCC. INTERVENTIONS: Evaluation of fresh BCC excisions by CLS microscopy. MAIN OUTCOME MEASURES: Diagnostic accuracy of the method was evaluated by chi2 test. Diagnostic impact and reliability of each morphologic feature were evaluated by logistic regression analysis and kappa statistic, respectively. RESULTS: Overall, high diagnostic accuracy was achieved by the 4 observers. Logistic regression analysis revealed that mainly tumor cell nuclei and tumor nests should be taken into account for diagnostic decisions, whereas disintegration of tumor cells, peripheral palisading, and retraction of stroma were rarely useful. However, most of the features were highly reliable. CONCLUSIONS: This diagnostic validation study of CLS microscopy in microscopy-guided surgery yielded promising results and opens avenues for further studies. In the future, CLS microscopy may guide microsurgery of any skin cancer.
Abstract: BACKGROUND: The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL). METHODS: We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20-71 years). RESULTS: Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance of alpha/beta-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-gamma gene showed a polyclonal smear in all cases. CONCLUSIONS: Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-gamma gene rearrangement.
Abstract: In the new World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification of cutaneous lymphomas, large B-cell lymphomas (LBCLs) are divided into 3 groups: LBCL, leg-type (LBCLLT); follicle center lymphoma, diffuse type (FCLDT); and LBCL, others (LBCLO). We studied a large number of primary cutaneous LBCLs to test the validity of the classification and to identify prognostic factors for these patients. Ninety-three cases of primary cutaneous LBCL were analyzed for clinicopathologic features, expression of several markers including Bcl-2, Bcl-6, MUM-1, and FOX-P1, in situ hybridization for Epstein-Barr virus, and molecular analyses of IGH gene rearrangement and of Borrelia burgdorferi and human herpesvirus 8 DNA. Patients were classified into the following categories: FCLDT, 44 cases; LBCLLT, 40 cases; and LBCLO, 9 cases. Statistical analyses showed that the LBCLLT and FCLDT groups were clearly distinct in terms of clinicopathologic features and survival. The LBCLO group had features in between those of LBCLLT and FCLDT. Our study shows that accurate morphologic and phenotypic analyses allow us to stratify most patients into the prognostically different categories of LBCLLT and FCLDT. The definition of a third category of LBCLO requires further studies to clarify whether these cases indeed show distinct clinicopathologic features.
Abstract: A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic T-cell lymphomas of the skin has been recently described, and some have been included as distinct clinicopathologic entities in the classification of hematologic malignancies recently proposed by the World Health Organization. In the European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas, they would be classified either as CD30- large T-cell lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell lymphoma. Precise clinicopathologic and prognostic features of all of them have not yet been well characterized. We studied retrospectively 81 biopsies from 50 patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non-mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic, phenotypical, and genetic features and data on Epstein-Barr virus association allowed us to classify our cases according to the following 7 categories: a) subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5-year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated 5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated 5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified: 2 cases. Our study shows that these cutaneous lymphomas can be classified according to precise diagnostic categories. With the exception of SPTCL, analysis of follow-up data from our patients showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.
Abstract: BACKGROUND: Patients with Hodgkin's and non-Hodgkin's lymphomas may develop non-infectious granulomas in both involved and uninvolved organs, but rarely in the skin. Cutaneous granulomas in the setting of a systemic lymphoma are of two types. The first type is characterized by granulomatous infiltrates admixed with neoplastic cells within specific skin lesions of malignant lymphomas. The second type consists of granulomatous skin processes that are non-specific manifestations of the underlying lymphoma. OBJECTIVE: To describe the variegate histologic patterns of cutaneous granulomatous reactions of the second type in patients with systemic lymphomas. METHODS: We describe three patients with systemic lymphomas who exhibited three different histologic patterns of cutaneous granulomatous lesions. RESULTS: The first patient had non-Hodgkin's lymphoma with cutaneous tuberculoid-type granuloma mimicking tuberculoid leprosy; the second patient had Hodgkin's lymphoma with palisaded, necrobiotic granuloma of granuloma annulare-type; and the third patient had non-Hodgkin's lymphoma with sarcoid-type granuloma. No evidence of the underlying systemic lymphoma was found in the cutaneous lesions involved by the granulomatous process. CONCLUSIONS: Cutaneous granulomas may be a non-specific sign of an underlying systemic lymphoma. Their histologic patterns are variegate and include sarcoid-type granuloma, palisaded and necrobiotic granuloma of granuloma annulare-type, and tuberculoid granuloma. In patients who present with non-infectious, granulomatous skin reactions in the absence of another sound explanation, the possibility of a systemic lymphoma should be considered.
Abstract: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma characterized in its early stages by a superficial band-like infiltrate with epidermotropism of lymphocytes without particularly atypical cytologic features. Even though clinicopathologic presentation is diagnostic in typical cases, some inflammatory skin disorders can simulate the histopathologic features of early MF. In this study we present data on 9 patients affected by lichen sclerosus (LS) (M:F ratio 8:1; age range 7-75 years; mean age 31.3 years; median age 13 years), who presented with histopathologic features simulating early lesions of MF. The histopathologic picture was characterized in all cases by a dense, band-like infiltrate of lymphocytes within the superficial dermis, with exocytosis of lymphocytes within the lower part of the epidermis. The papillary dermis was expanded and showed focally coarse bundles of collagen simulating MF. The typical signs of LS were either absent or present only focally. Molecular analyses of the TCRgamma gene rearrangement performed with the polymerase chain reaction (PCR) technique revealed a polyclonal smear in eight cases, and a monoclonal band in one. Our study shows that LS can present with histopathologic features simulating early MF. Especially in cases revealing a monoclonal population of T lymphocytes by PCR, the correct diagnosis may be overlooked without proper clinical information and clinicopathologic correlation. Lichen sclerosus should be added to the list of cutaneous T-cell pseudolymphomas.
Abstract: The gastrointestinal tract, particularly the oesophagus, is affected in about half of all patients with systemic sclerosis. Only a few studies so far have dealt with the anorectal tract. We studied the anal function using anorectal manometry in 12 patients with limited systemic sclerosis. We also studied the oesophageal function. For the oesophagus, we measured the difference between intragastric and oesophageal pressure, while for the anorectal tract we investigated the maximum resting pressure, the maximum voluntary squeeze effort and the rectoanal inhibitory reflex. Maximum resting pressure and maximum voluntary squeeze effort were found to be decreased in all patients. The rectoanal inhibitory reflex was abnormal in four patients. Statistical analysis showed a significant correlation between maximum resting pressure and maximum voluntary squeeze effort. No correlation was found between oesophageal and anorectal involvement. Anorectal dysfunction is common in patients with limited systemic sclerosis. We suggest that these patients should have an evaluation of their anorectal function including anorectal manometry.
Abstract: Solitary dermatofibromas are a common occurrence, especially on the lower limbs of young women, while multiple dermatofibromas (MDF) are rare, accounting for less than 0.3% of all dermatofibromas and may suddenly develop in immunosuppressed patients. We report a patient with systemic lupus erythematosus (SLE) who developed MDF while she was taking oral prednisone. A 46-year-old woman presented in 1989 complaining of photosensitivity, arthralgias, fatigue, malaise and dyspepsia. The patient denied fever, Raynaud's phenomenon, oral ulcer and hair loss. On examination she presented a typical SLE malar rash. Erythrocyte sedimentation rate (ESR) was elevated (54 mm/h). Speckle patterned IgG/IgM antinuclear antibodies were present at 1/1280 titer. Antibodies anti Ro/SSA were detected by counterimmunelectrophoresis up to 1/8 titer. Other laboratory findings were negative or within normal limits. Systemic lupus erythematosus was diagnosed and the patient given 50 mg/day prednisone. After a few months, both clinical symptoms and immunologic parameters improved. Eighteen months later, prednisone was replaced by 500 mg/day hydroxychloroquine. In 1994, she presented again with malar rash, arthralgias and facial hyperpigmentation. Prednisone 15 mg/day was reintroduced and hydroxychloroquine stopped being a possible cause of the facial hyperpigmented macules. In 1996, while she was taking 5 mg/day prednisone, several nodules developed on her limbs within a few months. On examination we observed 16 firm, slightly elevated 3-15-mm wide brown nodules on her arms, legs and trunk. A biopsy specimen of a lesion of the trunk revealed an epidermal seborrheic-keratosis-like hyperplasia with dermal fibrosis and fibroblastic proliferation (Fig. 1). Dermatofibroma was diagnosed.
Abstract: Common warts (verrucae vulgaris) are associated with human papillomavirus infection and are routinely treated by ablative procedures such as cryotherapy, electrodessiccation and salicylic acid. We report 10 cases of recurrent warts treated with a potential new topical therapy, imiquimod 5% cream. Nine of the 10 patients were successfully treated with imiquimod 5% cream applied, under occlusion, once daily for 4 weeks. No recurrences were reported during 3 months of follow up.
Abstract: The Systemic Lupus Activity Measure (SLAM) is a system proposed by rheumatologists to measure disease activity in their patients with systemic lupus erythematosus (LE). It involves scoring a group of clinical symptoms and laboratory findings, the maximum possible score being 84. In systemic LE, the mid-point is between 9 and 12. We applied SLAM to 176 patients with cutaneous LE. Ninety-seven had localized discoid LE (L-DLE), 59 had disseminated discoid LE (D-DLE) and 20 had subacute cutaneous LE (SCLE). Eighty-five patients had low activity disease (0-4 points), 72 mildly active disease (5-9 points), 15 moderately active disease (10-14 points) and only four had very active disease (>/= 15 points). The most frequent lesions in patients who scored more than 10 points were photosensitivity, cicatricial alopecia, Raynaud's phenomenon and oral ulcers. Fifty patients were followed up for more than 5 years (mean follow-up 9 years). Nine of these had an increased SLAM score. Seven had L-DLE, one D-DLE and one SCLE. Seven of the 50 patients had photosensitivity, five cicatricial alopecia, five non-cicatricial alopecia, two Raynaud's phenomenon and two oral ulcers. Three patients who started with L-DLE evolved to D-DLE. The SLAM system is useful in the monitoring of disease activity in patients with cutaneous LE. Over time, even L-DLE patients may develop active disease. Photosensitivity, alopecia, oral ulcers and Raynaud's phenomenon seem to herald a worse prognosis.
Abstract: A 34-year-old woman presented with a right winged scapula 8 months after developing systemic lupus erythematosus (SLE) with subacute cutaneous manifestations. The patient experienced severe shoulder pain followed by weakness of the right arm in the typically winged scapula fashion. Electromyography of the serratus anterior showed long thoracic nerve palsy. Clinical and laboratory signs did not reveal any associated disease. Paralysis of the long thoracic nerve has never been described before in SLE.
