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Background: The literature on paediatric mycosis fungoides (MF) and especially its folliculotropic variant (FMF) is sparse., Objectives: To describe the clinical manifestations, treatments, outcomes and long-term course of paediatric MF, including FMF., Methods: A retrospective analysis was conducted of all consecutive MF patients diagnosed at ≤18 years attending two medical centres in 1995-2015., Results: The cohort included 71 patients, all but two of whom had early-stage disease: hypopigmented (55%), folliculotropic (42%) and classical MF (39%), alone or in combination. The head and neck area were involved in 43% of patients with early-stage FMF compared to 12% of the non-FMF group (P = 0.004). There was no difference in the involvement of other body areas between the groups. Pruritus, although mild, was more often recorded among patients with early-stage FMF compared to non-FMF (58% vs. 29%, respectively, P = 0.02). Complete response (CR) was achieved in 60 of the 69 patients with early-stage MF (87%) after an average of 1.8 treatment modalities. NBUVB was the most administered treatment to non-FMF patients with CR rates of 63% vs. 29% of FMF patients (P = 0.04). Systemic/bath PUVA and UVA+NBUVB were the most administered treatments to FMF patients with CR rates of 60% vs. 81% for non-FMF patients (P = 0.17). During a mean follow-up of 9.2 years (range 1-24), stage progression was observed in four (6%) of the patients with early-stage disease, two of whom (all FMF) to advanced stage., Conclusions: Paediatric MF presents as an early-stage disease with over-representation of hypopigmented and FMF variants. NBUVB and UVA-based therapies yield good response rates in non-FMF and FMF patients, respectively. Disease course is indolent, and even on relatively long follow-up, it has a very low progression rate from early to advanced-stage disease, occurring in patients with FMF. We propose a treatment algorithm for paediatric MF., (© 2022 European Academy of Dermatology and Venereology.)

Background: Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, and nodules/tumors. Previous reports of PCBCL manifesting with macular lesions are scarce and focused on primary cutaneous follicle-center cell lymphoma (PCFCL)., Objectives: The objective of this study was to report our experience with PCBCL presenting with erythematous macules., Methods: Patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 through December 2019 at 2 tertiary cutaneous-lymphoma outpatient clinics, were included. Clinical data were retrospectively collected, and biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed., Results: There were 14 patients, aged 16-67 years, 8 had PCFCL and 6 marginal zone lymphoma (PCMZL). All had 1-15 cm erythematous macules, mimicking: interstitial granuloma annulare/vascular tumors/early-stage folliculotropic mycosis fungoides, or presenting with figurate erythema or livedo reticularis-like/net-like pattern. In 3 patients, macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients, typical PCBCL lesions were observed during disease course. The macules showed in all, superficial and deep perivascular infiltrates, and in most, periadnexal infiltrates. Micronodules were observed in 11 specimens, with nodular infiltrates also observed in 4. B cells comprised the majority of the lymphocytes in only 4. Seven of 11 cases tested showed immunoglobulin heavy chain monoclonality., Conclusions: PCMZL and PCFCL may manifest with erythematous macules. Physicians should be aware of this unusual manifestation of low-grade PCBCL, which may represent a clinicopathological diagnostic pitfall., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background/purpose: This study examined clinical and histological parameters of primary dermal melanoma (PDM) to aid in its distinction from dermal metastasis., Methods: Retrospective analysis of a prospective cohort of PDM patients. Includes patients fulfilling the strict histologic criteria for PDM ( N = 9) and patients who did not, but clinically, unequivocally had an intradermal melanoma-clinical PDM (cPDM; N = 17).Histopathology slides were re-examined. Prognosticators and outcome measures were compared between groups. Sentinel nodes' retrieval and wide local excision (WLE) were offered to all patients as primary treatment., Results: 26 patients identified, 15 females with a median age of 69 years (range 3.5-85). Mean Breslow was 7.9 ± 5.7 mm (median 5.8, range 1.8-25.0), and the mean mitotic rate was 4.9 ± 3.8/mm 2 (median 4.0, range 0-17). Initial treatment and follow-up were as for cutaneous melanoma. One patient in each group with a palpable stage III underwent primary radical dissection. Sentinel nodes were retrieved in all 20 lymphatic mappings performed and found to be metastatic in 5 (25%) patients. Treatment consisted of completion lymph-node dissection. At a median postoperative follow-up of 62 months (range 8-132), 20 patients were disease-free, including 6 of 7 patients with stage III disease at presentation. Six patients died all of cPDM; 5 of 6 patients had primary ulcerated or epidermal-abutting melanomas., Conclusions: This is the first study to highlight cPDM. Diagnosis requires expert pathology review and a tight correlation to the clinical parameters. Patients seem to benefit from WLE with sentinel node retrieval and complete dissection when appropriate. However, clinical guidelines for dissection have changed since the time period of this retrospective review. Based on this series, complete nodal dissection in these melanomas is associated with better than expected outcome, for stage III disease.

Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF. Immunohistochemical analysis revealed a significantly increased number of dermal Ki-67+ proliferating lymphocytes in tumour-stage FMF, together with an increased number of CD20+ B cells and CD68+ macrophages compared with early-stage FMF. Thus, similar to classic MF, miR-155, Ki-67 tumour cell immunoreactivity, and certain tumour-infiltrating inflammatory cells are differentially expressed in early- vs tumour-stage FMF. The results of this study corroborate the notion that FMF presents with 2 distinct stages.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated., Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL., Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment., Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4-22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001)., Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Background: The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown., Objectives: To investigate the microRNA profile in unilesional MF distinguishing it from early MF., Methods: Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA-binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively., Results: Unilesional MF had a significantly higher level of expression of all members of the microRNA miR-17~92 cluster than early MF. Specifically, unilesional MF had a higher miR-17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR-17~92 members; higher gene expression of interleukin-2 and interferon-γ; and a statistically lower average percentage of GATA3 + dermal cells (6·7% vs. 42·3%), were detected in unilesional MF compared with early MF. High immunoreactivity of CXCR3 was noted in both unilesional and early MF., Conclusions: Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR-17~92 members along with Th1 skewing. These findings suggest a robust reactive T-cell immune response in unilesional MF and might account for the localized nature of this disease., (© 2018 British Association of Dermatologists.)

Data on the treatment of early folliculotropic mycosis fungoides, a recently defined clinicopathological subgroup of folliculotropic mycosis fungoides with an indolent course, is limited. Treatment outcomes were studied in a retrospective cohort of 47 adults with early folliculotropic mycosis fungoides, with a focus on psoralen plus ultraviolet A (PUVA) monotherapy, including dosimetric data, and the findings were compared with data for PUVA in 18 adults with early-classic mycosis fungoides. PUVA was given to 27 patients with early folliculotropic mycosis fungoides: 70% achieved complete response and 26% partial response. Significantly more treatments were needed to achieve complete response in stage IB compared with stage IA. There was no significant difference in the complete response rate from classic plaque-stage disease, although the early folliculotropic mycosis fungoides group required more treatments to achieve complete response, and a higher cumulative dose of UVA. Thus, PUVA is an effective treatment for early folliculotropic mycosis fungoides. Its complete response rate might be equal to early-classic mycosis fungoides; however, a longer induction phase is needed to achieve complete response.

Amelanotic melanomas (AMMs) account for a small proportion of all melanomas. They pose a risk of delayed diagnosis and, consequently, poor prognosis. AMMs may atypically present as a pyogenic granuloma-like lesion. This study sought to investigate the prevalence and clinical and histological features of AMM masquerading as pyogenic granuloma. The database of a tertiary medical center was screened for all patients pathologically diagnosed with melanoma in 2005-2016. Those with a suspected primary (i.e. pre-excision) clinical diagnosis of pyogenic granuloma were identified, and their demographic, clinical, histologic, and outcome data were collected from the medical files. Of 2038 patients diagnosed with melanoma, 10 (∼0.5%) had a pyogenic granuloma-like AMM. The mean±SD age at lesion presentation was 56±18.9 years and the mean time from lesion appearance to diagnosis was 91.5±117.1 months. Nine tumors were located on the skin surface, and one on the oral mucosa. The mean lesion size was 19.6±14.1 mm and the mean Breslow's depth was 6.47±3.1 mm; all tumors presented in the vertical growth phase. Seven (70%) patients had lymph node involvement or metastasis at diagnosis. Two patients died of the disease within 1 year of diagnosis. Given the potential lethality of AMM and the benign nature of pyogenic granuloma, clinician recognition of pyogenic granuloma-like AMMs is crucial. In the presence of a pyogenic granuloma-like lesion, findings of older patient age and large tumor size should raise the index of suspicion and prompt a biopsy study, thereby ensuring early and accurate treatment.

Nevi and melanocytic proliferations are known to appear in multiple extracutaneous sites, including lymph nodes and meninges. We report a case of an anterior mediastinal mass in a patient with a giant congenital nevus and neurofibromatosis type I. Histologically, the tumor was found to be a malignant melanoma in the thymus arising in association with a nevus that involved most of the thymic tissue. There was no sign of cutaneous melanoma on skin examination. We suggest that the tumor originated from the benign nevus in the thymus, a rare extracutaneous location for nevi and malignant melanoma.

Background: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) has rarely been reported in patients younger than 20 years., Objectives: To report our experience with PCMZL in the paediatric/adolescent age group., Methods: Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were reviewed., Results: The study group included 11 patients (six girls; median age 16 years, range 6-19·5); 10 had generalized/multifocal (T3) and one had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in six; two had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included nonradiation modalities: one patient with localized disease received intralesional steroids; six patients with multifocal disease received the following: topical/intralesional steroids (n = 3); excision (n = 2); 'watch and wait' (n = 1). No extracutaneous progression was noted during a median follow-up of 5·5 years (mean 7·5, range 0·5-14). At present, five patients are in complete remission., Conclusions: Based on our data (largest series in the literature with the longest follow-up), the clinicopathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to those in adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration., (© 2016 British Association of Dermatologists.)

Background: It is generally accepted that folliculotropic mycosis fungoides (FMF) is usually typified by indurated plaques and tumors mainly on the head/neck and an aggressive course. However, its clinical manifestations have long been recognized to be quite variable, and some studies indicate a better prognosis for certain presentations., Objective: We sought to summarize our experience with the clinicopathological presentations of FMF and impact on prognosis., Methods: Data were collected retrospectively for adults with FMF followed up prospectively at a tertiary medical center in 1995 through 2014., Results: In all, 34 patients presented with follicle-based patch/flat plaques, keratosis pilaris-like lesions, and/or acneiform lesions, defined clinically as early stage (IA, IB), and 15 presented with follicle-based infiltrated plaques and/or tumors, defined as advanced stage (IIB). The head/neck was involved in all tumor-stage cases, whereas early-stage lesions involved mainly the trunk/limbs. The tumor stage was characterized by more pruritus, heavier perifollicular infiltrates, greater vertical depth, and more frequent presence of eosinophils. On multivariate analysis, infiltrate density was the only significant histopathological discriminator between the stages. Estimated 5-year survival was 0.94 in the early-stage group and 0.69 in the tumor-stage group., Limitations: Lack of long-term follow-up and relatively small sample are limitations., Conclusion: FMF presents with 2 distinct patterns of clinicopathologic features, early stage and advanced stage, each with different prognostic implications., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Unilesional folliculotropic mycosis fungoides (UFMF) has been rarely reported., Objective: The aim of this study was to describe our experience with UFMF., Methods: Data were collected on all patients with clinicopathological UFMF who attended the Department of Dermatology of a tertiary university-affiliated medical centre in 1996-2013 and were followed prospectively., Results: The sample included seven patients (five male, two female) of mean age 38 years at diagnosis; two were aged <18 years. The lesion presented as a solitary patch/plaque with follicular accentuation in five patients, an infiltrated plaque devoid of hair in one and with follicular nodules in one. Four patients had alopecia, and one, secondary anetoderma. The lesion was located on a limb in four patients, the trunk in two, and the face in one. In all cases, the atypical folliculotropic lymphocytes expressed mainly surface CD4(+). Monoclonality was detected in three of the six patients analysed. Treatment consisted of localized electron beam in five patients, all of whom had a complete response (CR), and excision in one patient. The remaining patient, a 9-year-old boy, was treated with topical psoralen and UVA with CR. The duration of follow-up was 0.5-10 years (mean 4). There were no recurrences in six patients and local recurrence in one., Conclusion: UFMF presents at a young age, usually with early disease clinical morphology. The treatment goal should be cure. Our experience indicates an excellent prognosis of early UFMF with no multifocal/internal spread., (© 2014 European Academy of Dermatology and Venereology.)

Background: The literature on mycosis fungoides (MF) in children/adolescents is sparse., Objective: We sought to evaluate the characteristics of juvenile MF in a large cohort., Methods: Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively., Results: There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA., Limitations: Relatively short follow-up is a limitation., Conclusions: This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Unlike T-cell neoplasms, B-cell lymphoproliferative disorders have a limited clinical spectrum of skin involvement. Cutaneous B-cell neoplasms mimicking rosacea or rhinophyma are rare., Observations: We described 12 patients with B-cell lymphoproliferative neoplasms presenting with a facial eruption clinically mimicking rosacea or rhinophyma. Eleven patients were women; ages ranged from 36 to 81 years. The clinical presentation included small papules on the nose and cheeks and around the eyes mimicking granulomatous rosacea; nodules on the nose, cheeks, chin, or forehead mimicking phymatous rosacea; or a combination of both. Three patients had preexisting erythematotelangiectatic rosacea and 1 had rhinophyma. Based on a clinicopathologic correlation and B-cell clonality analysis, the diagnosis was primary cutaneous follicular center B-cell lymphoma in 4 cases, primary cutaneous marginal zone lymphoma in 6, and skin involvement of chronic lymphocytic leukemia in 2. All patients had an indolent course as expected for their disease., Conclusions: Cutaneous involvement of B-cell neoplasms may mimic granulomatous rosacea or rhinophyma. This unusual clinical presentation is more common in women and appears in the setting of preexisting rosacea or as a new eruption. Proliferative B-cell disorders should be added to the differential diagnosis of symmetric papular or papulonodular eruptions of the face.

erbB receptors contribute to tumor formation and progression. Variable expression of erbB1, erbB2, and erbB3 has been reported in nevi and melanomas; erbB4 has hardly been investigated. We examined the expression of all 4 erbB receptors in common and dysplastic nevi and melanomas. Formalin-fixed, paraffin-embedded tissues of 100 melanomas, 27 common nevi, and 23 dysplastic nevi were immunostained with antibodies against the 4 erbB receptors. erbB3 and erbB4 showed stronger positivity in nevi than in melanomas, and in common than in dysplastic nevi. Staining pattern was more orderly in nevi than in melanomas. Common nevi showed more prominent membranous staining for erbB3 than dysplastic nevi followed by melanomas. In melanomas, greater thickness was associated with more widespread erbB2 and erbB3 staining in the vertical than in the radial growth phase, and in the dermal than in the epidermal component. Higher mitotic counts were associated with more widespread and intense erbB2 expression in the vertical growth phase than in the radial growth phase and in the dermal than in the epidermal component. Melanomas with more widespread erbB2 staining had heavier lymphocytic infiltrates. erbB1 expression was negligible in all groups. erbB2, erbB3, and erbB4 are expressed in all subtypes of melanocytic lesions, but with quantitative and qualitative differences. Receptor expression seems to decrease and to become less mature and orderly with tumor progression. The complex patterns of erbB receptor expression in melanocytic lesions warrant further investigation.

Background: Primary cutaneous B-cell lymphoma manifested by anetoderma has been reported in 7 cases. In all, the secondary anetoderma developed in lesions of marginal-zone lymphoma or posttransplant lymphoproliferative disorder resembling marginal-zone lymphoma. The mechanisms underlying the destruction of elastic tissue in anetoderma are unclear. However, there is growing evidence linking primary anetoderma with a wide range of immunologic abnormalities, the most common being the presence of antiphospholipid antibodies., Observations: We analyzed data from 5 patients (3 male, 2 female) with clinical and histopathological features of anetodermic primary cutaneous B-cell lymphoma. Three had marginal-zone lymphoma and 2 had follicle-center cell lymphoma. In all, secondary anetoderma developed in self-regressing nodules/plaques of the lymphoma. Two patients also had lesions clinically and histopathologically compatible with primary anetoderma. Associated immunologic diseases were systemic lupus erythematosus-like disease and rheumatoid arthritis (1 patient each; not in patients with primary anetoderma). Antiphospholipid antibodies were found in 4 patients., Conclusions: Anetodermic primary cutaneous B-cell lymphoma is a rare and unique clinicopathological manifestation not only of marginal-zone lymphoma, as previously described, but also of follicle-center cell lymphoma. This type of secondary anetoderma, like primary anetoderma, might be associated with immunologic disorders, particularly antiphospholipid antibodies.

Background: Cutaneous lymphomas rarely occur in children and adolescents, and are mostly of the T-cell lineage. Low-grade primary cutaneous B-cell lymphoma (CBCL) is extremely rare in individuals under 18 years old. Only 11 patients under 20 years old have been reported in the literature., Objectives: To evaluate the number of patients younger than 18 years with primary CBCL diagnosed at our centre and to investigate its clinicopathological features, treatment and course in this age group., Methods: We reviewed the files of all 90 patients with primary CBCL who attended the Department of Dermatology of our tertiary care university-affiliated centre from 1992 to 2007., Results: Four patients who met study criteria were identified: three girls and one boy. Mean age at diagnosis was 16.6 years (range 16-17). Three patients had cutaneous marginal zone lymphoma (CMZL), and one had a spindle-cell (sarcomatoid) lymphoma, most probably follicular centre cell type. All were treated with the standard regimen used in adults. The mean duration of follow up was 45 months. No extracutaneous progression was noted. At present two of the four patients are in complete clinical remission., Conclusions: In Israel, primary CBCL apparently occurs more often in young patients than reported in the literature. CMZL is the most frequent type. Long follow up is mandatory to assess the biological behaviour of CBCL in the paediatric/adolescent age group.

Cyclooxygenase-2 (COX-2) is involved in the development and progression of many tumors, and its inhibition has been shown to block tumor growth. This study examined COX-2 expression in primary and metastatic Merkel cell carcinoma (MCC). Formalin-fixed paraffin-embedded tissues from 26 primary MCCs and 7 lymph node metastases were stained immunohistochemically with a monoclonal antibody directed against COX-2, and the percentage and intensity of staining were analyzed semiquantitatively. Immunopositivity for COX-2 was found in 20 primary tumors (77%), and was diffuse in 16 of them (80%). Staining intensity was strong in 5 tumors (19%), moderate in 6 (23%), and weak in 9 (35%). Five metastases (71%) showed similar staining. Prominent mitotic activity was associated with more diffuse COX-2 immunopositivity. No association was found between COX-2 expression and outcome. This study confirms that most MCCs express COX-2 and shows that COX-2 expression is related to one parameter of aggressive behavior--a high mitotic rate--but not to any others. The possibility of treating MCC with COX-2 inhibitors should be considered.

Background: Acral lentiginous melanoma (ALM) is associated with low survival., Objective: The aim of the study was to compare the clinical course of ALM, non-ALM hand and foot melanoma, and melanoma of the extremities in nonacral locations., Methods: Data on 168 patients operated on for cutaneous melanoma of the extremities from 1993 to 2005 were examined. Twenty-nine had ALM, 16 non-ALM, and 123 other-extremity melanoma. All known melanoma prognosticators were analyzed for their impact on survival at a median of 53 months' follow-up., Results: The ALM group was significantly older (p=.015). No differences between the ALM and non-ALM groups were noted in tumor characteristics, lymph node status, and survival. However, the other-extremity melanoma group presented with significantly thinner lesions, fewer positive sentinel lymph nodes, and lower tumor stage and, consequently, had significantly better disease-specific and disease-free survival (p=.006, p=.0001). The acral lesions were nearly free of peritumoral lymphocytic infiltration. Multivariate analysis identified only tumor thickness (p=.0127), stage (p=.00001), and patient age (p=.012) as independent prognosticators of disease-specific survival., Conclusion: Cutaneous melanomas in acral sites, regardless of histology, tend to be diagnosed at an advanced stage probably owing to older patient age, difficult-to-see sites, and biologic factors, leading to reduced patient survival.

Background: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) occasionally resemble each other histologically but differ in histogenesis and biological behavior. This study sought to determine if these lesions can be differentiated by the quantity or quality of expression of cyclooxygenase-2 (COX-2), an enzyme associated with both reactive and neoplastic processes., Patients and Methods: Formalin-fixed and paraffin-embedded samples from 20 DFs and 20 DFSPs were stained immunohistochemically with antibodies directed against COX-2. Staining was evaluated semiquantitatively for percentage and intensity using a three-tiered system. DFs were graded and analyzed by cellularity. Findings within the tumors were compared with fibrocyte staining in adjacent tissue. The results were analyzed., Results: Nineteen DFs (95%) and 15 DFSPs (75%) were immunopositive for COX-2; this difference was not statistically significant. Highly cellular DFs showed more widespread (p = 0.0039; r = 0.614) and more intense (p = 0.0586; r = 0.429) staining than less cellular DFs and more prominent staining in adjacent fibroblasts (p = 0.044; r = 0.608)., Conclusions: COX-2 immunostaining does not distinguish DFs from DFSPs. However, the enzyme is expressed more widely and more intensely in more cellular, possibly younger, DFs. The prominent expression of COX-2 in DFSP may have clinical implications for treatment with COX-2 inhibitors in tumors that are not amenable to surgery.

Background: Capillary malformations (also known as port-wine stains) are low-flow vascular malformations of the skin that occur in 0.3% of neonates. Angiolipomas are subcutaneous, benign, usually multiple, lesions, composed of adipose tissue and blood vessels, which occur in young adults., Objective: The aims of this study were to determine whether there is an association between capillary malformations and angiolipoma, and to describe the characteristics of patients with this association., Methods: Prompted by our finding of an accompanying subcutaneous mass in a patient with capillary malformation, we reviewed the entire pool of 127 patients (71 women, 56 men; average age 22.2 years) attending the Rabin Medical Center (Petach Tikva, Israel) for treatment of nonfacial capillary malformations. All patients underwent a detailed history and comprehensive physical examination. Biopsy samples were taken from suspect lesions., Results: In addition to the index patient, four patients were found to have a subcutaneous mass beneath the capillary formation. Imaging and histologic studies identified the mass as an angiolipoma. All of the lesions were relatively refractory to pulsed dye laser or intense pulsed light treatment., Conclusion: This unique report of an association between capillary malformation and angiolipoma is intended to raise the index of suspicion for underlying angiolipoma in clinicians treating patients with refractory nonfacial capillary malformations.

Background: Non-Hodgkin's lymphoma (NHL) coincident with pregnancy is rare, and the literature regarding mycosis fungoides (MF), the most common primary cutaneous NHL, and pregnancy is strikingly sparse. The effect of pregnancy on MF, or on parapsoriasis en plaque (PPP), and the effect of these diseases on pregnancy, are still unknown., Objective: To study the effect of pregnancy on MF and PPP and the impact of these diseases on pregnancy., Methods: The files of the MF and PPP patients seen during the past 12 years in our department were reviewed to search for patients who had been pregnant during the course of their disease., Results: Nine women who met the study criteria were identified, seven with early-stage MF and two with PPP. A total of 12 pregnancies was recorded: nine in patients with MF and three in patients with PPP. In none of the patients was there any indication that pregnancy changed the course of MF or PPP. Of the 12 pregnancies, 11 were normal; one was naturally aborted. Two of the patients were treated with topical steroids during pregnancy. One patient was treated with narrow-band ultraviolet-B combined with topical steroids. The rest preferred to avoid any therapy., Conclusions: Pregnancy appeared to have no impact on the course of early MF or PPP, and no adverse effect was noted on pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF or PPP.

Background: The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse., Objectives: To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms., Methods: Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period., Results: Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled., Conclusions: This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Background: The familial occurrence of mycosis fungoides (MF) has been reported only in 8 families. Recently, the HLA class II alleles DRB1* 11 and DQB1* 03 have been found to be significantly increased for patients with sporadic MF, suggesting a possible immunogenetic basis for the pathogenesis of this malignancy., Objective: We sought to detect familial occurrences of MF, to describe familial features, and to investigate the possible association or linkage with the HLA system in such cases., Methods: The files of 300 patients with MF were reviewed to search for familial occurrence in at least two first-degree relatives. A group of 252 healthy unrelated individuals served as control subjects. Tissue typing for HLA class I was performed using the microlymphocytotoxicity technique. DNA-based analysis for DRB1* and DQB1* alleles was performed using polymerase chain reaction amplification., Results: Six families comprising 12 Jewish patients (9 male and 3 female) were detected: in 5, two first-degree relatives had MF; and in one, one member had MF and another had parapsoriasis en plaque. There were 5 families with two affected siblings and one family with a parent-child pair. In all but one family, the age of onset, clinical features, and response to therapy were similar to those in sporadic MF. One family, however, was exceptional: both affected siblings were children and both exhibited a similar but unusual morphology in the form of a hypopigmented variant of MF in conjunction with a psoriasiform variant. The allele frequency of HLA DQB1* 03 was found to be significantly greater among the patients than in the control group (66.7% vs 33%, respectively; P = .027), supporting an association of this allele with familial MF. Analysis of the HLA typing in the affected sibling pairs, when grouped together, did not support linkage to the HLA locus because no segregation distortion could be demonstrated ( P = .76)., Conclusions: Familial aggregation of MF among Israeli Jews may not be as rare as is reflected in the literature. This familial clustering, together with the detection of certain HLA class II alleles with this malignancy (sporadic and familial), suggests that genetic factors may play a role in MF.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.

Background and Aim: Sentinel lymph node biopsy (SLNB) is reportedly associated with insignificant morbidity. The study aims at documenting SLNB-related complications and identifying possible risk factors., Method: Data of all melanoma patients who underwent SLNB in our medical center (1994-2002) were analysed. Procedure-related complications were recorded., Results: Three hundred and nine lymphatic basins of 250 patients were explored for SLNB. Overall complication rate was 20%. Sensory morbidity was significantly associated with axillary SLNB (p=0.04) and was more prevalent in younger patients. The use of blue dye alone or combined with a hand-held gamma probe had no statistically significant impact on the identification rate. There were six false-negatives (2.3%), for an overall false-negative rate of 18%. A positive sentinel node was significantly associated with shortened overall survival (p=0.04)., Conclusion: Wound complications are more frequent than usually reported. Sensory morbidity occurs mostly in the axilla. Neck SLNB is associated with the highest rate of identification failure. Patient age, basin location, and number of excised nodes may serve as prognostic factors of morbidity.

Background: Climatotherapy at the Dead Sea (CDS) is a well-established therapeutic modality for moderate to severe psoriasis vulgaris, resulting in sustained remissions. It has also been found to be effective for atopic dermatitis, another T-cell-mediated dermatosis., Objective: We sought to prospectively evaluate the efficacy of CDS in patch-stage mycosis fungoides., Methods: A total of 12 patients with patch-stage mycosis fungoides (6 with stage IA and 6 with stage IB) were treated with CDS as monotherapy for 28 consecutive days according to the protocol for psoriasis, ie, a gradual increase of sun exposure to a maximum of 3 hours daily., Results: A total of 9 patients achieved a complete clinical response (CCR), defined as no disease activity present; 2 achieved an almost CCR, defined as the reduction by more than 90% of disease activity; and 1 achieved a partial response, ie, reduction by more than 50% of disease activity. A CCR was achieved in all the patients with stage IA disease and in 3 of the 6 patients with stage IB disease. Of the 9 with a CCR, 6 also showed histopathologic clearing. Duration of the remissions, during which no therapy was allowed except for emollients, lasted from 2 to 9 months (mean: 5 months). No serious short-term side effects were recorded., Conclusion: CDS appears to be an effective, well-tolerated therapy for patch-stage mycosis fungoides.

Background: Acquired ichthyosis is a known paraneoplastic sign of lymphoproliferative malignancies, with histopathologic findings that are nonspecific, revealing no insinuation of the underlying neoplasm. Ichthyosiform eruption as a specific manifestation of mycosis fungoides (MF), ie, ichthyosiform MF, is, however, regarded as rare and to date has been reported in only a few cases., Objective: We sought to study the clinical, histopathologic, immunohistochemical, and genotypic features of patients with ichthyosiform MF., Methods: The files of patients with MF seen during the past 8 years in our department were reviewed to search for cases of ichthyosis-like MF., Results: Seven patients, comprising 3.5% of the patients seen with MF, had an ichthyosiform eruption with histopathologic features characteristic of early MF. In 2 patients it was the sole manifestation of the disease and in 5 patients it appeared either in conjunction with conventional patches and/or plaques or with follicular lesions. Immunohistochemically, all showed a predominance of CD3+ CD4+, except for 1 patient in whom the epidermotropic T cells were predominantly CD8+. In 3 of the 7 patients clonality could be demonstrated by polymerase chain reaction. None had extracutaneous involvement. All had an indolent course of the disease and responded well to skin-targeted therapies., Conclusions: Ichthyosiform MF is yet another atypical clinical variant of cutaneous T-cell lymphoma that is not as rare as reflected in the literature. It may be the sole manifestation of the disease but also may appear in conjunction with conventional or follicular MF lesions.

Keratinocytes influence the number, morphology, and proliferation of melanocytes. An interference in the melanocyte-keratinocyte relationship may contribute to melanoma development. This study examined the expression of apoptotic and proliferative markers in keratinocytes in lentigo maligna to characterize the epidermis permissive to these lesions. Formalin-fixed and paraffin-embedded tissues from 25 samples of lentigo maligna, 20 samples of solar keratoses, and 5 samples each of normal sun-exposed and non-sun-exposed skin (controls) were immunostained with antibodies directed against the proapoptotic markers bax and p53, the antiapoptotic marker bcl-2, and the proliferation marker ki-67. Eight percent of the lentigo maligna samples were positive for keratinocyte expression of bcl-2, 24% were positive for p53, and 76% were positive for bax; respective findings for solar keratoses were 35%, 85%, and 90%. Comparison with normal sun-exposed skin yielded lower rates of keratinocyte proliferation in 56% of the lentigo maligna samples, similar rates in 36%, and higher rates in 8%; for solar keratoses, proliferation was higher than controls in 60% of samples, similar in 35%, and lower in 5%. All these differences were statistically significant. These findings indicate that there are variable patterns of epidermal reaction to chronic sun exposure. The epidermis in lentigo maligna shows overall low proliferation and an apparently low apoptotic tendency. The dysfunctional epidermis may be permissive to aberrant melanocyte proliferation in the early stages of melanoma development.

The literature regarding mycosis fungoides in children is sparse. To shed further light on the characteristics of mycosis fungoides in the paediatric population we analysed the clinicopathological features of 10 patients in whom this malignancy was diagnosed before the age of 18 years. All were Jews and Arabs with histologically proven patch/early plaque stage disease: 4 in stage IA, 4 in IB and 2 with unilesional disease. Seven patients had hypopigmented lesions either constituting the sole manifestation (2 patients) or in combination with classic lesions (5 patients); of these, 3 had light skin and 4 pigmented skin. Most patients had immunohistochemical features characteristic of mycosis fungoides, with a predominance of CD4+ T cells. Some had deletion of CD7+ cells. In 3 patients, however, the epidermotropic cells were exclusively or predominantly CD8+ cells. All patients responded to conventional therapy and during an average follow-up of 3.4 years only one patient showed stage progression, but without extracutaneous involvement. It is concluded that juvenile mycosis fungoides is characterized by early stage disease, occasionally with unilesional disease, usually with hypopigmented lesions irrespective of skin colour, and a good response to therapy. On the basis of our experience and review of the literature, it appears that the CD8+ phenotype is over-represented in juvenile disease.

Malignant melanomas, which produce a large number of substances active in connective tissue modulation, must contend with the dermis to grow and propagate. We studied the morphologic interactions between tumorigenic malignant melanomas and dermal elastin. Formalin-fixed and paraffin-embedded tissues of 108 tumorigenic malignant melanomas were stained for elastic tissue with the Verhoeff-van Gieson method. Various aspects of the relationship between malignant melanoma and dermal elastin were analyzed in relation to the histologic and clinical data using univariate and multivariate analyses. Tumor thickness, mitotic rate, and the presence of elastin remnants within the tumors were found to be independent negative prognostic factors, the latter with borderline significance. Tumors with more remnants of elastin were associated with higher stage of disease and lymph node and distant metastases. Tumor infiltration between the elastic fibers in the tumor depth was associated with high Clark level, greater tumor thickness, high stage of disease, and lymph node metastases. At least partial preservation of elastic fibers in the tumor depth was a relatively good prognostic factor whereas complete absence of elastin was an adverse factor. Focal or multifocal absence of elastin in the midst of the tumors or in their depth was usually associated with lymphocytic infiltrates. We suggest that tumors with remnants of elastic fibers and/or invasion between elastic fibers in their depth may be fast growing and highly invasive. The absence of elastin within tumors and at their advancing edge may be related to the elaboration of elastin-degrading substances by melanoma cells or various inflammatory cells. Our findings indicate that the relationship between malignant melanomas and dermal connective tissue components, specifically elastin, may have prognostic significance.

We describe four patients with mycosis fungoides (MF) in whom depigmentation, and also leucotrichia in one, occurred following the resolution of the eruption during phototherapy (psoralen plus ultraviolet A treatment in three patients, climatotherapy in one). In all cases, the depigmentation was localized to the area of the pre-existing MF lesions. There was no clinically obvious phototoxicity. Biopsy study including S100 staining in all cases, and electron microscopy in one case, demonstrated the total absence of melanocytes, with no evidence of MF. It is suggested that the phototherapy may have activated a cell-mediated immunity leading to destruction of the melanocytes. We recommend that vitiligo-like leucoderma be added to the list of untoward effects of phototherapy in MF.

Background: Merkel cell carcinoma (MCC) has been associated with a high incidence of other skin tumors and hematological malignancies. The purpose of this study was to analyze data from the Israel Cancer Registry regarding the incidence of second neoplasms in patients with MCC and their impact on survival., Methods: Sixty-seven patients in whom MCC was diagnosed between 1983 and 1999 were included. Data were collected on age, gender and ethnic origin, dates of diagnosis of MCC and any other neoplasm, and date and cause of death, if applicable. Comparison of MCC-specific survival, estimated by the Kaplan-Meier product limit method, between patients with no other neoplasm and those with second primary tumors was performed by log rank test. Age-specific standardized incidence ratio (SIR) was calculated using 5751 age- and ethnic-matched malignant melanoma patients as a control group., Results: Seventeen patients (25%) had a second neoplasm before, concomitant with, or after the diagnosis of MCC; 2 of them also had a third primary tumor. The SIR was 2.8 (95% CI; range, 1.38-4.22), significantly higher than the control group. Almost half the tumors were squamous cell carcinomas, either skin or head and neck, and most of the remainder were hematological malignancies or breast and ovarian adenocarcinomas. On univariate analysis, the presence of another neoplasm, regardless of its chronology, was associated with higher MCC-specific mortality (65% vs. 40% for patients with MCC only; P = 0.022). Analysis of only those patients in whom a second neoplasm developed during follow-up after treatment for MCC yielded an estimated actuarial risk of developing a second primary of 2.1% for each year of observation., Conclusions: There is a high incidence of second neoplasms, including noncutaneous solid tumors, in patients with MCC. The presence of these neoplasms, whether they appear before, after, or simultaneously with MCC, is associated with a higher MCC-specific mortality., (Copyright 2001 American Cancer Society.)

Identification and histologic study of the sentinel node (SN) is an acceptable, yet not firmly established, guide for treating intermediate-thickness melanoma. This study widens the range of applications of this technique. We included 97 patients with intermediate-thickness melanoma lesions or lesions for which there is no standard treatment. Fifty-six underwent preoperative lymphoscintigraphy, and all underwent intraoperative lymphatic mapping (IOLM) using blue dye, followed by frozen section study and total node processing by serial sections. Elective lymph node dissection was performed in cases of metastasis to the sentinel node or technical failures with high risk. Four categories were defined: (A) intermediate-thickness lesions (mean 2.27 mm) (n = 45); (B) thin lesions (mean 1.14 mm) with risk factors of regional failure (n = 27); (C) lesion thickness close to but more than 4 mm (n = 10); and (D) lesions of undetermined thickness (n = 15). Median follow-up was 30 months (range 13-51 months). Intraoperative lymphatic mapping successfully identified the sentinel node (SN) in 93% of basins explored. Metastases were detected in 11 SNs. There were three lymph basin recurrences in patients with previously negative SNs, all salvaged by therapeutic lymph basin dissection and are NED (no evidence of disease). Two SN(+) patients had systemic recurrences; one died of his disease, and the other is alive with disease. One SN(-) patient died NED owing to other cause. This technique spared 83% of category A patients from lymph node dissection. It allowed better staging and better decision making for treatment in categories B and D; and it prevented early regional recurrences in category C patients. Intraoperative lymphatic mapping with SN guidance is a novel, lo

Background: Merkel cell carcinoma (MCC) resembles malignant melanoma in several ways. Both are cutaneous lesions of the same embryonic origin. Both have an unpredictable biologic behavior, early regional lymph node involvement, early distant metastases, and high recurrence rate., Objective: To apply the sentinel node technique described for melanoma to MCC in light of the common biologic features of these two tumors., Methods: Preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and sentinel node biopsy and frozen section histology were performed to guide the surgical treatment of three patients with MCC., Results: Application of this approach in patients with MCC is feasible, reproducible, and seems reliable., Conclusion: The use of the sentinel node technique for MCC will reduce the number of unnecessary lymphadenectomies, will enable identification of microscopic metastases to lymph nodes, and will improve the stratification and accrual of patients into adjuvant treatment protocols. It may even lead to a survival benefit.

Background: Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized by a solitary lesion clinically and by histopathological features indistinguishable from those of MF, and typically having a benign course., Objective: To describe the clinicopathological features of a series of patients with unilesional MF., Methods: The records of cases of unilesional MF identified during a 10-year period in two medical departments were reviewed., Results: There were 7 patients: 6 males, 1 female; mean age at the time of diagnosis: 32 years; age range: 12-58 years; 3 were below the age of 18 years. The mean pretherapy follow-up period was 9 years (range: 2-20 years). In 5 patients, the eruption consisted of a characteristic patch or plaque of MF located on the trunk or upper extremity; in 2 it was atypical - in 1, a hypopigmented patch, and in 1, a plaque indistinguishable from MF-associated follicular mucinosis. Histopathologically all the lesions exhibited features characteristic of MF, with CD3+ lymphoid cells. In 6 cases (with available fresh frozen tissue) there was a predominance of CD3+ CD4+ cells; in 1 of 5 there was deletion of CD7, and in 3 of 5 there was an overexpression of IL-2 receptor. T-cell receptor gamma gene rearrangement was found in 1 of 4 cutaneous lesions tested; in 2 cases it was found in the blood but not in the skin. Treatment modalities included localized electron beam, excision, topical nitrogen mustard or topical steroids and sunbathing, resulting in all cases in a sustained complete clinical response. In 1 patient, however, there were 2 local recurrences and in yet another patient there was distant cutaneous spread 3.5 years after therapy., Conclusions: Unilesional MF is a rare variant of CTCL, has heterogeneous clinical manifestations and can affect any age group, including children. The histopathological and immunophenotypical features are in general indistinguishable from those observed in multilesional MF. Although it is a unifocal event, there may occasionally be cutaneous spread with the appearance of noncontiguous lesions, even a long time after therapy. Whether all cases represent minimal-stage IA MF or whether some are actually T-cell pseudolymphoma remains to be clarified., (Copyright 2000 S. Karger AG, Basel)

Chemotherapy and radiation therapy act predominantly through the induction of apoptosis in malignancies. Merkel cell carcinoma, an aggressive malignancy with prominent apoptosis, has proved to be sensitive to both modes to a certain degree. We used immunohistochemical methods to examine 25 Merkel cell carcinomas and 8 of their lymph node metastases to assess the status of the antiapoptotic gene bcl-2 and 2 proapoptotic genes, wild-type p53 and bax. All tumors showed prominent bax immunopositivity; 76% were positive for bcl-2, and only 28% were positive for p53, the latter presumably reflecting mutated p53. No statistically significant relationship was found between tumor immunopositivity and therapy response or survival. The widespread bax immunopositivity and the apparently low rate of p53 mutations, as suggested by the low rate of p53 immunopositivity, may be related to the presence of prominent apoptosis in Merkel cell carcinoma. The finding of bcl-2 immunopositivity in 76% of the tumors suggests that some of the tumor cells may be resistant to apoptosis-inducing agents.

Merkel cell carcinoma is an aggressive neuroendocrine skin tumour. Treatment is still debatable. Merkel cell carcinoma resembles malignant melanoma in its cutaneous presentation and its embryonic origin; both have unpredictable biological behaviour, early regional lymph node involvement, early distant metastases and a high recurrence rate. In light of these common features, we used pre-operative lymphoscintigraphy, intraoperative lymph-node mapping and sentinel-node biopsy-a well-described technique for the treatment of melanoma-in a 60-year-old man with Merkel cell carcinoma in the right buttock. Following frozen section identification of a metastatic first-order sentinel node, radical right groin dissection was performed. All the other lymph nodes in this basin proved to be disease-free, including the second-order sentinel node and Cloquet node. The patient is now being treated with adjuvant chemotherapy and radiotherapy. This case shows that sentinel-node guided dissection is applicable to Merkel cell carcinoma., (Copyright 1999 W.B. Saunders Company Ltd.)

Nine patients with follicular cutaneous T-cell lymphoma (CTCL), a recently described variant of lymphoma, are presented. On the basis of clinical manifestations and disease course, three groups of patients were distinguished: (i) two patients with follicular CTCL not associated with conventional lesions of mycosis fungoides (MF) and showing no evolution towards MF in follow-up periods of 3 and 6 years; (ii) one patient with follicular CTCL that evolved into conventional MF within 3 years; (iii) six patients showing conventional MF lesions either before or concurrently with the follicular lesions and thus representing follicular CTCL of the true MF type. The follicular lesions included hair-devoid patches or plaques with spiky hyperkeratotic papules (four patients), keratosis pilaris-like lesions (four), comedo-like lesions (four), follicular papules with alopecia (three) and milia-like lesions (three). Histopathological examination showed perifollicular and intrafollicular lymphocytes, without mucin deposition and with minimal or no involvement of the overlying epidermis. Significant syringotropism was also observed in three cases. Immunohistochemical analysis showed the predominance of CD4 + T cells, deletion of CD7 in some cases, Ki-67 + lymphocytes confined mainly to the follicular epithelium, and expression of keratinocyte intercellular adhesion molecule-1 exclusively in the hair follicle. T-cell receptor gamma gene rearrangement was positive in the one case studied from each group. Different treatment modalities were employed, the most commonly used as monotherapy being phototherapy: psoralen ultraviolet A in four patients, two of whom showed a complete clinical and histopathological remission, and ultraviolet B in one patient, who showed a complete remission (both clinical and histopathological). This study indicates that follicular CTCL is more common than reflected in the literature, has heterogeneous clinical manifestations, and is either an expression of or closely related to MF. The influence of the follicular involvement on the therapeutic response remains to be clarified. However, our therapeutic experience clearly suggests that some patients with follicular CTCL can benefit from phototherapy.

In many neoplasms, the finding p53 immunoreactivity correlates with striking cytologic atypia, a high tumor cell proliferation rate, and poor prognosis. The literature regarding p53 and Ki-67 (a nuclear proliferation-associated antigen) immunoreactivity in Kaposi's sarcoma is limited. We aimed to: (1) evaluate the role of p53 in the development of Kaposi's sarcoma; (2) determine whether there is a correlation between p53 and Ki-67 protein expression; and (3) determine possible differences between classical Kaposi's sarcoma, known usually to have a benign course, and iatrogenic Kaposi's sarcoma, the course of which is unpredictable, by studying the differential expression of p53 and Ki-67. Among 26 cases of classic KS and 19 of iatrogenic KS, 12 were classified histopathologically as early type and 33 as mixed or spindle-cell type. P53 and Ki-67 immunoreactivity correlated significantly with the histopathologic stage of KS (r=0.63, p=0.0001; r=0.42, p=0.0084, respectively). P53 was not detected in any of the cases in an early histopathologic stage but was present in 55% of the cases in a more advanced stage. The spindle cells increased in proportion with the histopathologic progression and were more often positive (p=0.019) and displayed more extensive staining than the endothelial cells (p=0.0001). There was a strong positive correlation between p53 and Ki-67 protein expression (r=0.43, p=0.0087). There was no correlation between the expression of either p53 or Ki-67 and the extent of the eruption. The expression of p53 and Ki-67 was significantly lower in iatrogenic cases than in the classic cases (p=0.009, p=0.0014, respectively), although no statistical difference was found between the histopathologic stages in the two clinical forms of KS. P53 immunoreactivity was detected in 79% of the cases of classic Kaposi's sarcoma in the mixed or spindle cell stage but in only 21.5% of the iatrogenic cases showing the same histopathologic stage (p=0.001), and the percentage of spindle cells as well as the endothelial cells expressing p53 was higher in the classic cases than in the iatrogenic cases (p=0.0032, p=0.0142, respectively). We conclude that p53 immunoexpression is a marker of tumor progression in classic Kaposi's sarcoma but not in most cases of iatrogenic Kaposi's sarcoma. The proliferative activity of the tumor cells in classic Kaposi's sarcoma is much higher than in iatrogenic Kaposi's sarcoma. Our work implies that the molecular steps involved in classic and iatrogenic Kaposi's sarcoma differ.

The modulating effects of mesoderm on ectoderm during the embryonic period have been well documented. Some cutaneous conditions such as dermatofibroma with basaloid proliferation are examples of such a relationship. Seven cases of basal cell carcinoma (BCC) developing in port-wine stains and one case developing over an arteriovenous (AV) malformation have been reported. We report 3 elderly patients with BCC developing over AV malformations of the lower extremities. The association between BCC and AV malformation range from a chance association to a complex interaction between mesenchyme and epithelium, in which mesenchyme induces and modulates epithelial growth through the elaboration of specific growth factors (GF).

Merkel cell carcinoma is a rare and highly malignant skin tumor. We present the first report on the clinical and epidemiologic characteristics of Merkel cell carcinoma in Israel. Our findings, including average age of 69 years at diagnosis, equal sex distribution, disease location on sun-exposed skin, and an overall 3 year survival of 58%, are consistent with the data reported in the literature. Unique findings in our study were the predominance of Ashkenazic Jews and the excessive rate of second malignancies. This initial report on Merkel cell carcinoma in Israel emphasizes the need for increased awareness of this aggressive and potentially lethal skin malignancy.