Pseudolymphomatous cutaneous angiosarcoma: a rare variant of cutaneous angiosarcoma readily mistaken for cutaneous lymphoma

Cutaneous angiosarcoma is probably the most malignant neoplasm involving the skin. Three clinical variants of cutaneous angiosarcoma are recognized, including angiosarcoma of the scalp and face of elderly patients, angiosarcoma associated with chronic lymphedema, and postirradiation angiosarcoma. Histopathologically, these three variants of angiosarcoma show similar features, which consist of poorly circumscribed, irregularly dilated, and anastomosing vascular channels lined by prominent endothelial cells that dissect through the dermis. Focally, neoplastic endothelial cells show large, hyperchromatic, and pleomorphic nuclei, protruding within vascular lumina and creating small papillations. Usually, inflammatory infiltrate is sparse and consists of a patchy, perivascular lymphoid infiltrate around the neoformed vessels. In rare instances, cutaneous angiosarcomas may exhibit prominent inflammatory infiltrate, and the neoplasm may be mistaken for an inflammatory process, both from clinical and histopathologic points of view. We describe four examples of cutaneous angiosarcomas with dense lymphocytic infiltrates involving the neoplasm. Immunohistochemically, lymphocytes expressed immunoreactivity for CD3, CD5, and CD45 markers, whereas the germinal centers were positive for CD20, CD79a, and Bcl-6. The neoplastic endothelial cells expressed immunoreactivity for the CD31, CD34, podoplanin, Prox-1, Lyve-1, and D2-40. We discuss the possible relationship between neoplastic endothelial lymphatic cells and reactive lymphocytes. Cutaneous angiosarcoma with prominent lymphocytic infiltrate may be readily mistaken for cutaneous follicle center cell lymphoma or cutaneous pseudolymphoma.     

Cutaneous angiosarcoma mimicking xanthoma: a challenging histopathologic diagnosis with important consequences

Cutaneous angiosarcoma may show protean histopathologic features. Rare or uncommon variants include epithelioid, clear cell, granular cell, verrucous, pseudolymphomatous and signet‐ring cell types. Perhaps the rarest type consists of cutaneous angiosarcoma with xanthomization of neoplastic cells. We report an extraordinary case with almost all neoplastic cells exhibiting a xanthomatous appearance that was studied both histopathologically and immunohistochemically. We discuss the histopathologic differential diagnosis of foamy cell angiosarcoma with other neoplasms that may show similar histopathology.     

ALK‐positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient

Anaplastic large cell lymphoma (ALCL) either as primary cutaneous or nodal disease is rare in children and difficult to distinguish, which is important both prognostically and for treatment purposes. We present a case of anaplastic lymphoma kinase (ALK)+ skin‐limited ALCL that highlights this challenge and draws attention to pitfalls in assessing ALK status. The patient was an 11‐year old girl with a twice recurrent nodule on her right shoulder. Each biopsy revealed a deep infiltrate of atypical lymphocytes that expressed CD3, CD4, CD43, CD45RO and CD30. The initial biopsy was epithelial membrane antigen (EMA)+ with vague cytoplasmic ALK‐1 positivity by immunohistochemistry, while the second biopsy was EMA+ and nuclear ALK‐1+. Fluorescence in situ hybridization analysis for an ALK (2p23) rearrangement of the first specimen was negative, while an ALK gene rearrangement was present in the second specimen. Therefore, this case was treated as nodal ALCL, despite negative bone marrow and radiographic imaging studies. The patient was treated with combination chemotherapy and remains disease‐free. Demonstration of nuclear ALK‐positivity, ALK (2p23) gene rearrangement is suggestive of systemic ALCL. Without evidence of systemic disease, this case highlights challenges of skin‐limited ALCL, whose clinical behavior as either cutaneous ALCL systemic ALCL may not be immediately apparent.     

Acneiform primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoma with prominent necrosis

Primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoma (SMPTCL) is an indolent form of cutaneous lymphoma that usually presents in solitary fashion and is histopathologically characterized by nodular infiltration of small‐ to medium‐sized pleomorphic T‐cells. We report the case of a patient who presented with a 5‐year history of acneiform lesions on his face. Histopathologic examination of two lesions revealed a nodular infiltrate of small to medium‐sized lymphocytes with necrosis in the dermis. The proliferating cells were positive for CD2, CD3 and CD4 and negative for CD8, CD30 and CD56. They were positive for TIA‐1 and negative for perforin and granzyme B. The Ki67 proliferation index was approximately 10%. The neoplastic cells expressed programmed death‐1 and lacked expression of CXCL‐13, bcl‐6 and CD10. In situ hybridization for Epstein–Barr virus‐encoded RNA yielded a negative result. T‐cell receptor gene rearrangement showed identical T‐lymphocyte monoclonality in both lesions. In brief, we report a rare case of acneiform SMPTCL with prominent necrosis.     

Anetoderma in cutaneous marginal‐zone B‐cell lymphoma

Anetoderma is a rare condition, consisting of well‐circumscribed areas of slack skin, in which dermal elastic fibres are destroyed or deficient. We present the case of a 45‐year‐old man with a 25‐year history of deep nodules and plaques gradually progressing to areas of anetoderma. Histological examination found an infiltrate composed of neoplastic cells with lymphoplasmocytoid morphology. The cells were positive for CD20, CD38 and CD138, and there was a monoclonal kappa light chain gene rearrangement of plasma cells. A diagnosis of cutaneous marginal‐zone B‐cell lymphoma was made. The pathogenesis of anetoderma remains unknown, but it is possible that cytokines or other soluble factors produced by the infiltrating lymphocytes have a role in this process.     

Cutaneous granular cell angiosarcoma

The majority of cutaneous angiosarcomas display typical architectural features of irregular anastomosing vascular channels in the dermis and subcutis. Nuclei are usually hyperchromatic and pleomorphic but die volume of cytoplasm of the neoplastic cells is often small. Diagnosis can be made readily on an adequate biopsy. We recently experienced difficulty diagnosing an angiosarcoma composed predominantly of cells with abundant granular cytoplasm. We were able to compare the present case with sections obtained from the only other reported example. The architectural expression of an anastomosing vascular pattern in areas of tumor, combined with the positive staining for Factor VIII-related antigen (FVIIIRAg) and Ulex europaeus agglutinin-1 (UEA1) enabled us to make a diagnosis of angiosarcoma. The tumor failed to stain for the other endothelial markers (CD31 and CD34) which were positive in the original case. A marker for lysosomes (CD68) stained the granules in both cases. The granular cell variant of cutaneous angiosarcoma is very rare. Diagnosis is possible by recognizing the typical anastomosing neoplastic vascular channels at the periphery of the lesion, and by use of a combination of lectin (UEA1) and immunohistochemical (FVIIIRAg, CD34 and CD31) endothelial markers.     

Primary cutaneous signet-ring cell melanoma: a clinico-pathologic and immunohistochemical study of two cases

Signet-ring cell malignant melanoma is a rare histopathologic variant of malignant melanoma with only a few described cases. We report the clinical, histopathological, and immunohistochemical features of two cases of primary cutaneous signet-ring cell malignant melanoma. Neoplastic melanocytes showed abundant clear cytoplasm compressing the nuclei to the periphery, sometimes resulting in a signet-ring appearance. Immunohistochemically, neoplastic melanocytes in both cases expressed immunoreactivity for the usual melanocytic markers S-100 protein and Melan-A, although only the second case resulted HMB-45 positive. We review the literature about this rare cytologic variant of malignant melanoma and discuss the differential diagnosis with other cutaneous neoplasms that may show a signet-ring cell appearance of their neoplastic cells.     

Large CD30-positive cells in benign, atypical lymphoid infiltrates of the skin

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.     

Paucity of intraepidermal FoxP3‐positive T cells in cutaneous T‐cell lymphoma in contrast with spongiotic and lichenoid dermatitis

Background: FoxP3 is the most specific available marker for regulatory T cells (Tregs). Tumor‐associated FoxP3‐positive Tregs have been identified in various neoplasms, including cutaneous T‐cell lymphoma (CTCL). FoxP3 expression in CTCL varies across groups; few studies have compared CTCL with inflammatory conditions. Methods: Lesional skin biopsies from 20 patients with CTCL [13 mycosis fungoides (MF); 7 Sézary syndrome (SS)] and 22 with inflammatory dermatoses (11 spongiotic; 11 lichenoid or interface) were examined for FoxP3 expression by immunohistochemistry. Epidermal FoxP3‐positive lymphocytes were counted as a percentage of the total epidermal CD3‐positive T‐cell population. Results: FoxP3‐positive T cells composed the minority of infiltrate in all major categories. Lower numbers of epidermal FoxP3‐positive T cells were observed in CTCL, particularly MF, than in inflammatory dermatoses (P < .001). CTCL neoplastic T cells did not express FoxP3. Conclusion: FoxP3‐positive T cells are less frequently encountered in MF than in inflammatory dermatoses. FoxP3‐positive T cells occur in higher proportions in the dermis than in the epidermis and probably correlate with coexisting inflammatory components. CTCL neoplastic cells do not typically express a Treg phenotype and are associated with low numbers of FoxP3‐positive Tregs in the infiltrate. FoxP3 expression by immunohistochemistry may aid histologic evaluation of these conditions. Wada DA, Wilcox RA, Weenig RH, Gibson LE. Paucity of intraepidermal FoxP3‐positive T cells in cutaneous T‐cell lymphoma in contrast with spongiotic and lichenoid dermatitis.     

Congenital cutaneous lymphadenoma

Cutaneous lymphadenoma is an uncommon benign neoplasm often considered to be an adamantinoid variant of trichoblastoma. Lesions present in both sexes, between 14 and 87 years of age, and are mainly located on the head and neck. Cases in children are rare and there is only 1 previous case of a congenital lymphadenoma. An 8‐year‐old Asian girl presented with a congenital lesion on her forehead comprising 4 pink papules, the largest 5 mm in diameter. Microscopy revealed a well‐circumscribed tumor within the dermis and subcutis comprising well‐demarcated epithelial lobules of basaloid and clear cells with subtle peripheral palisading, growing in a collagenous stroma but lacking retraction artefact. A relatively dense accompanying predominantly lymphocytic inflammatory cell infiltrate including both T‐cells (CD3+) and B‐cells (CD20+) permeated the nodules and spilled into the stroma. CD68+ histiocytes and CD1a+ Langerhans cells were moderately numerous. This is the second case of congenital lymphadenoma which—in spite of its rarity in childhood—widens the diagnostic possibilities of cutaneous lymphoepithelial tumors in children.     

Erythema multiforme‐like lesions in primary cutaneous aggressive cytotoxic epidermotropic CD8+ T‐cell lymphoma: A diagnostic and therapeutic challenge

Primary cutaneous aggressive cytotoxic epidermotropic CD8+ T‐cell lymphoma is an extremely rare, rapidly progressing, cutaneous lymphoma, with frequent systemic involvement and poor prognosis, that still represents a diagnostic and therapeutic challenge, especially in the early stage. Herein, we report a case of an elderly woman with a fulminant course, who at onset presented with clinical and pathological features mimicking erythema multiforme (EM) and treated with cyclosporine that led to rapid deterioration with fatal outcome 6 months after disease onset. Histopathology showed a lichenoid, epidermotropic and nodular, angiocentric, dermal and subcutaneous infiltrate of sF1, CD8+, CD45RA+ small to medium‐sized atypical lymphoid cells, which strongly expressed cytotoxic markers. Monoclonal T‐cell‐γ receptor was clonally rearranged and array‐CGH showed numerous chromosomal imbalances. This case evidences the clinical, pathological and therapeutic challenges involved in this tumor. The first biopsy showed an interface dermatitis‐like pattern, revealing the deceptive features that early cutaneous infiltrates of this aggressive lymphoma may have. A high suspicion for aggressive CTCL and a low threshold for repeat biopsies should be maintained when faced with rapidly progressing and/or ulcerative EM‐like lesions, especially if immunomodulatory therapy is being considered.     

Cryptococcus‐like changes in the setting of vasculitis

Cutaneous vasculitis has many underlying causes, and the clinical and histological findings often overlap. Inflammatory vasculitis can mimic infection; however, distinction is critical for the timely institution of appropriate therapy. We present two patients who had generalized polymorphous eruptions whose cutaneous pathology showed vasculitis with unusual haloed yeast‐like cells within the inflammatory infiltrate, mimicking Cryptococcus. The unusual cells stained negatively with Gomori methenamine silver and periodic acid‐Schiff fungal stains, but positively for CD68 and had cytoplasmic reactivity with antibody to myeloperoxidase (MPO). Both patients had positive serum anti‐MPO antibodies. The first patient experienced a rapidly fatal course, whereas the second patient improved with prompt initiation of systemic corticosteroids. Interestingly, the second case had prior biopsy showing Sweet syndrome with crypotoccoid‐appearing cells. Cryptococcoid cells have been described previously in association with neutrophilic dermatoses, but not in the setting of vasculitis as was seen in our patients. Our cases add to the existing literature on crypotoccoid mimickers, and are the first to be reported in association with vasculitis.     

Oral involvement in lymphomatoid papulosis

Lymphomatoid papulosis is a cutaneous lymphoma with an indolent clinical behaviour characterized by chronic development of recurrent, self-limited lesions appearing as necrotic papules and with a pathology compatible with T cell lymphoma. Mucosal involvement by lymphomatoid papulosis is very rare but has been reported in the literature. It usually appears as ulcers in patients previously diagnosed of lymphomatoid papulosis. From a histological perspective it is characterized by an infiltrate of CD 30 positive atypical lymphocytes together with a mixed inflammatory infiltrate of eosinophils, neutrophils, histiocytes and plasma cells. We report the case of a man previously diagnosed of lymphomatoid papulosis that developed two ulcerated lesions in the tongue whose biopsy confirmed the diagnosis of oral involvement by lymphomatoid papulosis.     

Angiolymphoid hyperplasia with eosinophilia affecting the scrotum: A rare case report with molecular evidence of T‐cell clonality

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign entity of unknown pathogenesis. It often presents as painful or pruritic intradermal or subcutaneous red to brown papules or nodules on the head and neck of young adults. A 38‐year‐old man had a gradually enlarging and mild pruritic plaque on the scrotum for half a year. Pathological findings showed dermal proliferation of anomalous blood vessels lined by plump endothelium with a significant perivascular inflammatory infiltrate composed of lymphocytes, histiocytes, scattered plasma cells and many eosinophils. They were consistent with the diagnosis of ALHE. In addition, the inflammatory infiltrate was analyzed by immunohistochemistry and T‐cell receptor (TCR) gene rearrangement. They were mostly CD3⁺ T cells and a monoclonal T‐cell population. To the best of our knowledge, this is the first case of ALHE affecting the scrotum to be reported in the published work. We present this case to expand the anatomical distribution of this rare tumor. The molecular study of our case supports that ALHE might be a low‐grade T‐cell lymphoproliferative disorder.     

Epidermotropic marginal zone lymphoma simulating mycosis fungoides†

Cutaneous lymphomas can usually be distinguished by architectural features, where most atypical lichenoid infiltrates implicate cutaneous T‐cell lymphoma (CTCL). We report a case of an 80‐year‐old man who presented with asymptomatic golden brown patches and diffuse pink papules on his trunk, buttocks and hips. Biopsies revealed a lichenoid infiltrate and areas of epidermotropism. Although the overall architectural pattern was compatible with mycosis fungoides, the lymphocytes had a more monocytoid and plasmacytoid appearance, and there were interspersed mature plasma cells. Immunohistological studies revealed that the pleomorphic lymphocytes were predominantly B cells (CD20\+ and CD79a\+) with a subpopulation of smaller bland T cells (CD3\+). Moreover, the B‐cell immunophenotype was compatible with marginal zone differentiation (bcl‐2+, bcl‐6?, CD10? and CD5?) and showed a lambda light chain restriction, confirming monoclonality. These findings were diagnostic for cutaneous marginal zone B‐cell lymphoma (MZL) with epidermotropism an entity which has only been reported twice in the literature, once in the setting of primary cutaneous disease, and once as cutaneous involvement of systemic disease. This case illustrates a rare pattern of cutaneous MZL, and underscores the importance of immunophenotypic characterization of cutaneous lymphomas in order to prevent the misdiagnosis of a CTCL.     

CD30+ lymphoproliferative disorder with spindle‐cell morphology

Lymphomatoid papulosis (LyP) is classified as a CD30+ primary cutaneous lymphoproliferative disease. The phenotypic variability along the spectrum of CD30+ lymphoproliferative diseases is highlighted by the distinct histologic subtypes of LyP types A, B, C, and the more recently described types D, E, and F. We report the case of an elderly woman with a clinical presentation and histopathologic findings consistent with LyP, whose atypical CD30+ infiltrate uniquely demonstrated a spindle‐cell morphology. To our knowledge, this is the first reported case of LyP characterized by CD30+ spindle‐shaped cells, and may represent a new and distinct histologic variant of LyP.     

Angioimmunoblastic T‐cell lymphoma with a clonal plasma cell proliferation that underwent immunoglobulin isotype switch in the skin,coinciding with cutaneous disease progression

Plasma cell proliferations in specific cutaneous lesions of angioimmunoblastic T‐cell lymphoma(AITL) are very uncommon. Here, we report a case of clonal plasma cell proliferation in skin with heavy‐chain‐immunoglobulin‐isotype‐switch after cutaneous disease progression. Histopathologically, initial plaque lesions were suggestive of marginal‐zone B‐cell‐lymphoma. Nevertheless, this 77‐year‐old lady was diagnosed with AITL after the progression of skin lesions from plaques to nodular tumors. A lymph node biopsy confirmed the diagnosis. Both cutaneous specimens showed a polymorphic cellular infiltrate with atypical T‐cell‐lymphocytes arranged in a pseudonodular pattern that expressed CD3, PD1 and BCL6, with patchy expression of CD30. Interestingly, a slight IgG‐Lambda plasma cell component was seen at the periphery of the infiltrate in the first specimen which increased in number in the later nodular lesion, showing not only Lambda light chain restriction and IgG but also IgG4. PCR studies for IgH and TCR genes showed an IgH clonal peak on both skin lesions but not on lymph node biopsy. On the contrary, the same clonal TCR peak was found in the three specimens. Neoplastic follicular helper T‐cells within cutaneous‐specific microenvironment could be responsible for the modulation of the immunoglobulin isotype class switch change. Further studies are needed to support this hypothesis.     

Primary cutaneous follicular helper T‐cell lymphoma

Follicular helper T‐cells (TFH) represent a specific subset of CD4‐positive helper T‐cells that help B‐cells to differentiate into long‐lived antibody‐secreting plasma cells or memory B‐cells. The expression of TFH markers in neoplastic T‐cells, traditionally related to the angioimmunoblastic (AITL) subgroup of peripheral T‐cell lymphomas, is nowadays well‐known to be more widespread than previously thought. We report hereby a case of cutaneous T‐cell lymphoma in a 75‐year‐old woman, whose morphological and immunophenotypical features raises the differential diagnosis between cutaneous involvement by AITL and the recently described primary cutaneous T‐cell lymphoma with follicular helper‐phenotype.