Clinicopathologic and molecular features in cutaneous extranodal natural killer-/T-cell lymphoma, nasal type, with aggressive and indolent course.

BACKGROUND: Extranodal natural killer-/T-cell lymphoma, nasal type (ENKTCL-NT) is a highly aggressive lymphoma and prognosis is usually poor. The genetic background of primary cutaneous cases is poorly understood. OBJECTIVE: We sought to evaluate the clinicopathologic features of cutaneous ENKTCL-NT, and the prognostic significance of genomic copy number alterations. METHODS: Eight cases of cutaneous ENKTCL-NT (5 primary, 2 secondary, 1 no staging performed), including 2 patients with an unusually prolonged course of 5 and 23 years, were investigated using array comparative genomic hybridization. RESULTS: All patients presented with typical clinicopathologic features. Epstein-Barr virus was found in neoplastic cells in all specimens. Copy number alterations were detected in all 8 cases with losses on 6q (37.5% of cases) and 7p (37.5% of cases), and gains on 7q (37.5% of cases) being the most frequent. Complexity of array comparative genomic hybridization profile did not correlate with the course of the disease. However, an increase of copy number alterations was detected in sequential biopsy specimens of 1 long-term survivor. LIMITATIONS: This was a small case series retrospective study. CONCLUSION: Clinicopathologic features of cutaneous ENKTCL-NT are distinctive. Lower number of copy number alterations cannot be used as predictor for prolonged survival in cutaneous ENKTCL-NT.

Miliary and agminated-type primary cutaneous follicle center lymphoma: report of 18 cases.

BACKGROUND: Primary cutaneous follicle center lymphoma (PCFCL) presents usually with reddish nodules, plaques, and tumors on the head and neck area, particularly the scalp, and on the back. OBJECTIVE: We sought to describe a peculiar clinical variant of PCFCL. METHODS: We report a series of 18 patients (male:female = 7:11; median age 52 years; mean age 50.8 years; age range 27-75 years) with a clinical variant of PCFCL characterized clinically by multiple, miliary, or agminated papules predominantly on the head and neck. RESULTS: All patients presented with multiple erythematous, firm papules arranged in a manner that resembled millet seeds or collected together in small clusters. Lesions were located on the entire face in one patient (5.6%), the forehead in 8 (44.4%), the cheeks in 3 (16.7%), the preauricular region in two (11.1%), and multiple regions on the head and neck area in 3 (16.7%). The last patient had miliary papules on the entire face, back, upper aspect of arms, and scattered on the front of the chest. The initial diagnosis was never cutaneous lymphoma, and all patients had been treated unsuccessfully for different skin conditions including mainly rosacea, lupus miliaris disseminatus faciei, and persistent arthropod bite reaction. Microscopic examination confirmed the diagnosis of PCFCL in all patients. LIMITATIONS: Small number of cases and retrospective study are limitations. CONCLUSIONS: This peculiar clinical presentation of PCFCL is unusual and represents a pitfall in the clinical diagnosis. Dermatologists should be aware of this variant of PCFCL so as to treat patients timely and properly.

Clinicopathologic features of early lesions of primary cutaneous follicle center lymphoma, diffuse type: implications for early diagnosis and treatment.

BACKGROUND: Data on early lesions of primary cutaneous follicle center lymphoma (PCFCL), diffuse type are very limited. OBJECTIVE: We sought to elucidate the early clinicopathologic features of PCFCL, diffuse type. METHODS: Clinical, histologic, immunohistologic, molecular, and fluorescence in situ hybridization data from 24 patients with early lesions of PCFCL, diffuse type (male:female = 19:5; median age: 57 years) were determined. RESULTS: Lesions consisted mostly of solitary or clustered papules and small nodules located on the trunk (21 cases), arm (two cases), and scalp (one case). In 3 patients small papules were located at a distance from the main affected area. All biopsy specimens from early lesions showed aggregates of medium and large centrocytes admixed with small lymphocytes without formation of clear-cut lymph follicles. Staining for Bcl-2 was positive in only 7 cases, one revealing also a rearranged BCL2 signal by fluorescence in situ hybridization. Data on treatment and follow-up were available for 22 patients. At last examination 13 patients were in complete remission (median follow-up: 60 months), 6 were alive with skin disease alone (median follow-up: 60 months), two were alive with skin disease and bone-marrow or lymph node involvement, respectively, and one died of unrelated causes while in complete remission. LIMITATIONS: The retrospective study and the fact that patients were treated at different institutions are limitations. CONCLUSIONS: Early lesions of PCFCL, diffuse type present with characteristic clinicopathologic features. Dermatologists should be alert particularly to the early clinical manifestations of this lymphoma and to the presence of small, inconspicuous lesions at a distance from the main affected area in order to plan treatment properly.

Borderline CD30+ cutaneous lymphoproliferative disorder: report of a case with expression of cytotoxic markers and response to clarithromycin.

CD30+ cutaneous lymphoproliferative disorders (CLPDs) are usually characterized by a benign clinical course. The prognostic value of cytotoxic markers in these lymphomas has not been evaluated in large series. We describe a case of borderline CD30+ CLPD with cytotoxic phenotype, presenting in a 22-year-old male patient as an ulcer on the forearm. He reported having had similar ulcers on the buttock and thigh that spontaneously regressed over the course of 1 year. The lesion resolved with a single course of clarithromycin; a subsequent lesion, too, responded to clarithromycin, and no recurrences or systemic involvement have been documented in the 9-month follow-up. A conservative approach in the management of CD30+ CLPD is recommended. We believe that the anti-inflammatory and apoptotic effects of clarithromycin on T cells may have hastened the remission process.

[Cutaneous endometriosis--clinical case report]. / Endometriose cutânea - a propósito de um caso clínico.

CASE REPORT: A 26-year-old woman presented with a history of a dark red, asymptomatic, firm, dome-shaped tumor, approximately 2.5 cm in diameter. The nodule had been developing for one year near a scar in the lower abdominal wall. Her past medical history was significant for a caesarean section five years prior to presentation. Histopathological examination revealed numerous glands of various sizes exhibiting small to large lumina, surrounded by a cellular, edematous stroma composed of spindle-shaped cells or round large cells admixed with lymphocytes, plasma cells, and few eosinophils. COMMENT: Cutaneous endometriosis is a well recognized but uncommon entity, representing approximately 1 percent of all cases of ectopic endometrial tissue. It may arise spontaneously within the umbilicus or inguinal region, but the majority of lesions develop on surgical excisions of the abdominal and genital regions (cesarean sections, hysterectomy, laparotomy, laparoscopy, and episiotomy) in women of reproductive age. The pathogenesis of cutaneous endometriosis is still not clear and several theories have been put forward to explain its development. Despite its clinical rarity, cutaneous endometriosis is a well-known condition to dermatopathologists. Nevertheless, they should be aware of those unusual metaplastic changes that may represent a diagnostic pitfall.

Lupus miliaris disseminatus faciei: a case report.

UNLABELLED: A 33-year-old man presented to our clinic with asymptomatic red-brown, dome-shaped papules, distributed bilaterally on the central area of the face (forehead, lower portions of the eyelids, nasolabial folds, and perioral areas) these had evolved over a period of about 1 year. A skin biopsy, taken from a lesion on the forehead, revealed an epithelioid cell granuloma with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. The chest X-ray and the results of the laboratory studies were within normal limits; the Mantoux test was negative. The patient was treated with minocycline 100 mg/day for 4 months. There was significant clinical improvement, but papular lesions remained on the forehead. Later on, treatment with systemic steroids for 7 months resulted in the resolution of most lesions. COMMENT: Lupus miliaris disseminatus faciei (LMDF) is an uncommon, chronic, inflammatory dermatosis characterized by red-to-yellow or yellow-brown papules of the central face, particularly on and around the eyelids. Originally, LMDF was considered to be a variant of lupus vulgaris or a tuberculid because of the histology, but there has been no evidence to date supporting a link to tuberculosis. Some authors consider LMDF to be a granulomatous forms of rosacea. However, our case supports the concept that it is a distinct entity.

Annular lichen planus in association with Crohn disease.

BACKGROUND: Lichen planus is an idiopathic inflammatory disease of the skin and mucous membranes. Although the etiology is not established, it has been associated with autoimmune diseases, viral infections, drugs and dental restoration materials. However, the association with inflammatory bowel disease has been very rarely reported in the literature. CASE REPORT: A 19-year-old female patient presented with annular lesions on her upper body and limbs, with a sharply defined border and non-atrophic skin in the center. The lesions were hyperpigmented and had been stable for over one year. The histopathology confirmed the diagnosis of annular lichen planus. She had weight loss, occasional diarrhea, and a severe anemia. The investigation of these symptoms led to the diagnosis of Crohn disease and a sickle cell trait. Therapy with systemic corticosteroids and mesalazine controlled the intestinal disease, with concomitant improvement of the skin lesions. CONCLUSIONS: As lichen planus can be associated with other immunological disorders, the association with inflammatory bowel disease should be considered in the evaluation of the patient.

Lyme borreliosis in Portugal caused by Borrelia lusitaniae? Clinical report on the first patient with a positive skin isolate.

BACKGROUND: Borrelia lusitaniae was isolated from an Ixodes ricinus tick in Portugal in 1993 for the first time. Further, this borrelia genospecies has been found in ixodid ticks collected around the coasts of southern Portugal and North Africa. Its reservoir has not been defined yet. B. lusitaniae was isolated once until now from a patient with a long standing and expanding skin disorder. PATIENT AND METHODS: A 46-year-old Portuguese woman presented with a skin lesion on the left thigh which had evolved slowly over ten years. The patient reported limb paraesthesias, cramps, chronic headaches, and cardiac rhythm disturbances. History of tick bites was negative nor had the patient ever noticed a skin lesion comparable with erythema chronicum migrans. Skin biopsies were taken for histological evaluation, culture and DNA detection. Antibodies to borrelia were searched by indirect immunofluorescence assay and Western-blot. RESULTS: A bilateral carpal tunnel syndrome and local synovitis was diagnosed. Dermato-histology was normal, serology was negative. Spirochaetal organisms were cultured from a skin biopsy and identified as B. lusitaniae. The patient improved after a 2-week course of intravenous ceftriaxone; the skin lesions did not expand further. CONCLUSIONS: This culture confirmed skin infection by B. lusitaniae in a patient from Portugal suggests an additional human pathogen out of the B. burgdorferi sensu lato complex in Europe, particularly in Portugal.

Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients.

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.

Cartilaginous melanoma: case report and review of the literature.

Malignant melanoma can present a variety of histopathological patterns. Cartilaginous change in the absence of osteogenic differentiation is extremely rare in malignant melanoma, being among the least frequent of the wide range of melanoma histologic patterns. We report a case of a 47-year-old woman with a subungual nodule on her right great toe for many years. Histopathological examination of the lesion led to a diagnosis of malignant melanoma with cartilaginous differentiation devoid of concomitant osseous areas. It would appear that this unusual form of melanoma has a predilection for acral location, particularly the subungual region. Malignant melanoma with chondroid stroma should therefore be considered in the differential diagnosis of cartilaginous lesions of the toes and fingers. Careful examination of the overlying epidermis and identification of an in situ component of melanoma may be necessary in order to establish the correct diagnosis.

Pseudoxanthoma elasticum papillary dermal elastolysis: a case report.

PXE-PDE is a rare clinicopathological entity with few cases reported. It affects more often elderly women and is characterized by asymptomatic bilateral and symmetrical yellowish papules localized predominantly on the neck and supraclavicular regions. It is clinically similar to Pseudoxanthoma Elasticum. The authors report a case of a 64-year-old woman presenting asymptomatic, yellowish, non-follicular papules, affecting the occipital and the posterior region of the neck for 1 year. The patient denied pruritic or inflammatory changes, marked solar exposition or trauma on the affected areas. Routine laboratory studies: thoracic x-ray and ophthalmologic examination were normal. The histopathologic examination of a biopsy of one of the cutaneous lesions showed an absence of elastic fibers in the papillary dermis.The diagnosis of Pseudoxanthoma Elasticum-like Papillary Dermal Elastolysis (PXE-PDE) was made. Of great importance is the differential diagnosis with Pseudoxanthoma elasticum (PXE), but we have also to consider other elastolytic disorders: mid-dermal elastolysis (MDE), linear focal elastosis (LFE) and white fibrous papulosis of the neck (WFPN). Until know, there is no effective treatment for this pathology.

Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a neoplasm derived from precursors of plasmacytoid dendritic cells. Cutaneous involvement represents often the first manifestation of the disease. We studied 45 skin biopsies from 33 patients (M:F=7.25:1; median age: 71 y; age range: 30 to 89) with BPDCN to delineate histopathologic and immunophenotypic features of this disease. Patients presented with generalized (n=18), localized (n=6), or solitary (n=9) macules, plaques, and/or tumors. Staging investigations at presentation were negative in 20 patients. Unusual histologic features included a perivascular/periadnexal pattern (6 biopsies from 4 patients) and the presence of pleomorphism of neoplastic cells with blastoid cells admixed with elongated, twisted, or hyperchromatic cells (observed in 24 specimens). Negativity of 1 among the 4 markers CD4, CD56, CD123, and TCL-1 was seen in 11 biopsies, and of 2 markers in 4 biopsies. Staining for CD68 revealed positivity of the majority of cells in 1 and of scattered cells in 24/37 stained cases. Terminal deoxynucleotidyl transferase was observed in 22/37 stained cases. Staining for Bcl-6, MUM-1 and FOX-P1 revealed positivity of a variable proportion of neoplastic cells in 16/30, 19/29, and 21/23 cases, respectively. Our study shows that cutaneous lesions of BPDCN display a greater variability of morphologic and phenotypic features than recognized earlier. Discrete perivascular infiltrates, pleomorphic morphology of neoplastic cells, and unusual phenotypic profiles may be the source of diagnostic pitfalls. These atypical variants should be recognized to make an early diagnosis and to manage properly patients with this aggressive hematological disorder.

Cartilaginous melanoma: case report and review of the literature / Melanoma cartilagíneo: caso clínico e revisão da literatura

Malignant melanoma can present a variety of histopathological patterns. Cartilaginous change in the absence of osteogenic differentiation is extremely rare in malignant melanoma, being among the least frequent of the wide range of melanoma histologic patterns. We report a case of a 47-year-old woman with a subungual nodule on her right great toe for many years. Histopathological examination of the lesion led to a diagnosis of malignant melanoma with cartilaginous differentiation devoid of concomitant osseous areas. It would appear that this unusual form of melanoma has a predilection for acral location, particularly the subungual region. Malignant melanoma with chondroid stroma should therefore be considered in the differential diagnosis of cartilaginous lesions of the toes and fingers. Careful examination of the overlying epidermis and identification of an in situ component of melanoma may be necessary in order to establish the correct diagnosis.

O melanoma maligno pode apresentar uma grande variedade de padrões histopatológicos. A presença de diferenciação cartilagínea, na ausência de diferenciação osteogénica, é extremamente rara no melanoma maligno. O melanoma cartilagíneo está entre os padrões histológicos menos frequentes. Relatamos um caso de uma doente do sexo feminino de 47 anos de idade com um nódulo subungueal no 1º dedo do pé direito com muitos anos de evolução. O exame histopatológico da lesão revelou melanoma cartilagíneo, sem áreas de diferenciação osteogénica. Esta variante de melanoma parece ter predileção pela extremidades, sobretudo pela região subungueal. Assim, o melanoma maligno com diferenciação condróide, deve ser tido em consideração no diagnóstico diferencial de lesões acrais cartilagíneas. A observação cuidadosa da epiderme e a identificação de um componente do melanoma in situ podem ser necessários para estabelecer um diagnóstico correto.