Composite cutaneous lymphoma of diffuse large B‐cell lymphoma‐leg type and subcutaneous panniculitis‐like T‐cell lymphoma

Composite lymphoma (CL) is a rare disease defined by the occurrence of two distinct lymphomas within a single tissue at the same time. We present the case of an 89‐year‐old male with a clinical history of immunoglobulin M monoclonal gammopathy of undetermined significance. The patient presented cutaneous eruption of nodules on the right bottom and arm. An excisional biopsy revealed cutaneous infiltration composed of two components. The first one consisted of large B‐cells with CD20+/MUM1+/BCL2+ phenotype whereas the second one involved the subcutaneous fat in a panniculitic manner, and was CD3+/CD8+/granzyme B+/TCRβF1+. The final diagnosis was CL of primary cutaneous large B‐cell lymphoma‐leg type (PCLBCL‐leg type) and subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL). We report and characterize for the first time coexistent PCLBCL‐leg type and SPTCL in a patient.     

Spindle B‐cell lymphoma: a rare variant of follicle center lymphoma

Primary cutaneous follicle center lymphoma (PCFCL) is a common subtype of primary cutaneous B‐cell lymphoma (PCBCL). The prognosis of this subtype is favorable and recurrence is observed in up to 50% of patients. The dissemination to lymph nodes or internal organs is rare. In this study, two cases of rare variant of PCFCL are reported. Both cases presented with multiple erythematous nodules, plaques and some annular configurations. Histopathological examination revealed dermal lymphocytic infiltrates consisting of admixed centrocytes and centroblasts. Interestingly, spindle‐shaped cells with elongated nuclei, dispersed chromatin and scant cytoplasm were also detected. Immunohistochemical analysis revealed that all cells including the spindle cells were positive for CD20 and negative for CD3, CD43, CD10, CD34, CD68 and CD138. They were also negative for desmin and S‐100. They consistently expressed nuclear bcl‐6, but did not express bcl‐2. The histopathological and immunohistochemical examination suggest a rare case of primary cutaneous spindle cell B‐cell lymphoma (PCSBCL). Although few data is published about this rare subtype, PCSBCL is recently considered as a rare subtype of PCFCL. The prognosis and the nature of this peculiar subtype are not yet cleared. This indicates a great need for more investigations.     

Case of primary cutaneous peripheral T‐cell lymphoma,not otherwise specified,with characteristics of follicular helper T cells

We report a case of an 88‐year‐old woman with a decalvant, erythematous, ulcerated tumor extending from the right temporal to occipital region. Histopathological analysis revealed a dense infiltration of medium‐to‐large‐sized atypical cells throughout the entire dermis. The result of immunohistochemical analysis showed that the infiltrating T cells expressed programmed death‐1 (PD‐1), Bcl‐6 and CXCL13. Flow cytometry analysis showed that CD4⁺ PD‐1^hi T cells also expressed CD10, inducible T‐cell co‐stimulator and CXCR5. On the basis of the clinical appearance and the histopathological findings, we diagnosed the patient with primary cutaneous peripheral T‐cell lymphoma, not otherwise specified. Recently, the concept of primary cutaneous follicular helper T (TFH)‐cell lymphoma was proposed, and in this case, tumor cells clearly expressed TFH‐cell markers. Therefore, we considered this case to be a variant of the entity. Although this entity is still provisional, this case supports the new concept.     

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.     

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.     

Spindle‐cell variant of primary cutaneous follicle center lymphoma spreading to the hepatobiliary tree,mimicking Klatskin tumor

Primary cutaneous follicle center lymphoma (pcFCL) is an indolent type of primary cutaneous B‐cell lymphoma (pcBCL) rarely disseminating to other organs. PcBCL with spindle‐cell morphology has been described as a rare variant of pcFCL but the prognosis data of this variant is sparse. We report a rare case of spindle‐cell pcFCL with CD20⁺, CD79a⁺, CD3⁺, Bcl‐6⁺, Mum‐1^? and CD10^?tumor cells that infiltrated the hepatic hilum, mimicking a Klatskin tumor. On the basis of the sparse published data on spindle‐cell morphology of pcBCL, this growth pattern should elicit awareness of an increased risk of systemic involvement in the otherwise indolent pcFCL.     

Use of an expanded immunohistochemical panel to distinguish cutaneous Hodgkin lymphoma from histopathologic imitators

In lymph nodes, classical Hodgkin lymphoma can typically be distinguished from non-Hodgkin lymphoma (NHL) by the presence of Hodgkin and Reed-Sternberg cells that co-express CD30 and CD15. However, anaplastic large cell lymphoma (ALCL) and diffuse large B-cell lymphoma (DLBCL) can show identical features, and some cases of classical Hodgkin lymphoma lack CD15 expression, rendering them difficult to differentiate from CD30-positive NHL. The differential diagnosis of cutaneous Hodgkin lymphoma similarly includes ALCL and DLBCL, and, additionally, tumors of mycosis fungoides. Recent studies have shown that classical Hodgkin lymphoma is of B-cell origin in virtually all cases, and shows at least focal weak expression of the B-cell marker PAX5 and often focal weak expression and no expression of the B-cell markers Oct-2 and BOB.1, respectively. All three of these markers are almost invariably absent in T-cell lymphomas and are strongly expressed in B-cell lymphomas. We report a 40-year-old man with classical Hodgkin lymphoma who developed cutaneous nodules. A biopsy from one revealed Hodgkin/Reed-Sternberg cells with a similar immunophenotype to the diagnostic lymph node biopsy, namely CD30+/CD15+, diffusely but weakly PAX5+, focally weakly Oct-2+ and lacking BOB.1 expression, thereby confirming a diagnosis of cutaneous Hodgkin lymphoma. To our knowledge, this is the first report of the expression pattern of the combination of PAX5, Oct-2 and BOB.1 in the context of cutaneous involvement by Hodgkin lymphoma.     

Acral angiokeratoma‐like pseudolymphoma in a middle‐aged woman

Acral angiokeratoma‐like pseudolymphoma is a rare type of pseudolymphoma presenting as dark‐red papules on the hand or foot. We describe a 59‐year‐old woman who presented with an unusual unilateral, clustered aggregate of scaly violaceous papules on the toe with an indolent course. Skin biopsy showed a prominent vascular proliferation associated with a dermal infiltrate of monoclonally rearranged T‐follicular helper phenotype T‐cells, in keeping with CD4+ small/medium T‐cell lymphoproliferative disorder (SMPTC‐LPD). Based on the unique clinical morphology, distribution of the lesions and dermoscopic appearance, a clinicopathologic diagnosis of acral angiokeratoma‐like pseudolymphoma was favored. This case demonstrates the importance of clinicopathological correlation in such diagnostically challenging patients who present with overlapping features on the spectrum of pseudolymphoma and cutaneous T‐cell lymphoma.     

Systemic panniculitis‐like T‐cell lymphoma with involvement of mesenteric fat and subcutis

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is an uncommon non‐Hodgkins primary cutaneous lymphoma that typically presents as subcutaneous nodules on the extremities or trunk. Here, we report an unusual case of systemic panniculitic T‐cell lymphoma with predominantly mesenteric extra‐cutaneous involvement and an aggressive clinical course with histopathologic and immunophenotypic features that mimic SPTCL. This case serves to expand the body of literature regarding systemic SPTCL‐like disorders with prominent extra‐cutaneous involvement.     

Primary cutaneous CD8+ cytotoxic T‐cell lymphoma involving the epidermis and subcutis in a young child

CD8+ cytotoxic T‐cell lymphoma involving the skin represents a heterogeneous group of diseases that include subcutaneous panniculitis‐like T‐cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma, and ‘type D’ lymphomatoid papulosis. In this report, we describe a case of CD8+ cytotoxic T‐cell lymphoma involving both the epidermis and subcutis. The patient was a 6‐year‐old girl who presented with a 3‐year history of multiple plaques on her trunk and legs. The lesions had relapsed twice but responded well to prednisone. Histopathologic examination showed the proliferation of atypical lymphocytes in the epidermis, dermis and subcutaneous tissue. On immunohistochemical analysis, the atypical lymphocytes were positive for βF1, CD3, CD8, perforin, granzyme B and TIA‐1, but negative for T‐cell receptor (TCR) γ, CD4, CD30 and CD56. It was difficult to classify this tumor in terms of the known types of cutaneous lymphoma, and this case should be differentiated with subcutaneous panniculitis‐like T‐cell lymphoma and primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma.     

Extrafacial indolent CD8‐positive cutaneous lymphoid proliferation with unusual symmetrical presentation involving both feet

Indolent CD8+ cutaneous lymphoid proliferation represents a recently described entity among cutaneous T‐cell lymphomas that typically presents with solitary skin lesions on the face or at acral sites and usually follows an indolent clinical course. Histopathologically, this entity is characterized by a dense dermal infiltrate of non‐epidermotropic, small‐ to medium‐sized pleomorphic CD8+ T‐cells of the non‐activated cytotoxic phenotype showing a clear‐cut grenz zone and a low proliferation index. Distinction from otherwise aggressive T‐cell lymphomas bearing a cytotoxic CD8+ phenotype is fundamental. We herein present an unusual case of indolent CD8+ cutaneous lymphoid proliferation presenting in bilateral symmetrical distribution on both feet and lacking the otherwise described grenz zone. Our case widens the spectrum of possible clinical and histomorphological variations of this entity. Taking into account the distinctive and unique clinical and microscopic features of all hitherto published cases of indolent CD8+ cutaneous lymphoid proliferation we suppose that this lymphoma subtype has to be included as a new and distinct entity in the World Health Organisation (WHO)‐/European Organisation for Research and Treatment of Cancer (EORTC)‐classification of cutaneous lymphomas.     

Primary cutaneous CD4 positive small/medium T‐cell lymphoma with high proliferation index and CD30‐positive large lymphoid cells

Primary cutaneous CD4 positive small/medium pleomorphic T‐cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T‐cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T‐cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30‐positive large lymphoid cells, and few infiltrating CD8 positive T‐cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T‐cell markers bcl‐6 and PD‐1. There were approximately 20% CD30‐positive large lymphoid cells, and Ki‐67 showed a moderately high proliferation rate (～40%), mostly in the large lymphoid cells. CD8 infiltrating T‐cells were few (<5%). The patient had an indolent disease with complete response to radiation therapy. To the best of our knowledge, this is the first reported case of SMPTCL with an increased proliferation rate and large CD30+ cells that followed an indolent clinical course.     

CD8‐positive peripheral T‐cell lymphoma with aberrant expression of CD20 and concurrent in situ follicular lymphoma

A case of a 78‐year‐old woman with a CD8‐positive peripheral T‐cell lymphoma with aberrant expression of CD20 associated with follicular lymphoma in situ (FLIS) is reported. The neoplasm presented initially as cutaneous macules, papules, plaques and nodules. A skin biopsy was performed and the diagnosis of peripheral T‐cell lymphoma (PTCl) with aberrant expression of CD20 was made. The staging procedures included an excisional inguinal lymph node biopsy that showed findings similar to those of the previous diagnosis. In addition, FLIS was identified. The clinicopathologic features of PTCLs with aberrant CD20 expression involving the skin as well as this uncommon association are reviewed.     

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.     

Primary cutaneous follicular helper T‐cell lymphoma: diagnostic pitfalls of this new lymphoma subtype

The recently proposed entity of cutaneous follicular helper T (T_FH) cell lymphoma (CT_FHCL) harbors distinct clinical and histopathologic features. Here, diagnostic pitfalls are exemplified in a case report and by review of the literature. A 45‐year‐old patient developed rapidly growing nodules and plaques on upper arms and buttocks, which were initially misdiagnosed as primary cutaneous follicle center B‐cell lymphoma (CFCL). Consequently, systemic therapy with rituximab failed and consecutive skin biopsies revealed CT_FHCL (CD3+CD4+CD10+PD‐1+bcl6+ICOS+CXCL13+). Interestingly, the prima vista PD‐1‐positive and CD10‐positive tumor cells lost PD‐1 expression in follow‐up biopsies while retaining CD10, ICOS and CXCL13 expression. All biopsy specimens displayed an identical clonal T‐cell population. Initially, nodules were controlled by local radiotherapy and oral psoralen combined with ultraviolet A (PUVA) therapy. However, disease recurred and progressed rapidly with disseminated nodules. Treatment with bexarotene, methotrexate and polychemotherapy failed to stop disease progression. Finally, modified total skin electron beam radiation resulted in complete remission. Disease stabilized on maintenance therapy with bexarotene in combination with ultraviolet A (UVA) therapy. The case highlights that because of concomitant B‐cell stimulation, CT_FHCL clinicopathologically is prone to be mistaken for CFCL. Importantly, CT_FHCL might lose PD‐1 while retaining CD10 expression in later stages, which may lead to confusion in distinguishing CT_FHCL from CFCL.     

Primary cutaneous acral CD8 positive T‐cell lymphoma with extra‐cutaneous involvement: A long‐standing case with an unexpected progression

Primary cutaneous acral CD8+ T‐cell lymphoma (acral CD8+ TCL) is a new provisional entity characterized by acral skin lesions and an indolent course. We describe an extraordinary case characterized by relapsed nodules with CD8+ cytotoxic infiltrates on the left ear. After 35 years, the skin lesions spread to other acral sites, and a mass with the same histological features as the other skin lesions appeared on the nose. Multiple courses of chemotherapy led to stable disease. Histological examinations carried out at different times showed the gradual transformation of the neoplastic cells, with an increased proliferation index. Genomic analysis revealed losses in the regions harboring the genes involved in cell cycle control. This is the first case of an acral CD8+ TCL with a very long history of indolent nodular lesions progressing to extra‐cutaneous sites.     

Disseminated CD8‐positive,CD30‐positive cutaneous lymphoproliferative eruption with overlapping features of mycosis fungoides and primary cutaneous anaplastic large cell lymphoma following remote solitary lesional presentation

CD8‐positive, CD30‐positive cutaneous lymphoproliferative disorders constitute a rare subset of T‐cell lymphoproliferative conditions, including variants of primary cutaneous anaplastic large cell lymphoma (ALCL), mycosis fungoides, lymphomatoid papulosis type D, cutaneous gamma‐delta T‐cell lymphoma and cutaneous peripheral T‐cell lymphoma. These entities share overlapping clinical, histopathologic and immunophenotypic features, presenting both a clinical and pathological diagnostic challenge. Presented here is a 73‐year‐old man with a disseminated, indolent CD30+, CD8+ cutaneous lymphoproliferative disorder with overlapping clinical and histopathological features of both mycosis fungoides and primary cutaneous ALCL, as well as features of lymphomatoid papulosis. To our knowledge, this is the first case of a generalized CD8+, CD30+ eruption with features of both mycosis fungoides and primary cutaneous ALCL arising following an episode of solitary primary cutaneous CD8‐positive ALCL.     

Primary cutaneous T cell lymphomas: photochemotherapy immunomodulation with analysis of the inflammatory‐expansive cellular dynamic

Primary cutaneous T cell lymphomas (CTCLs) are characterized by hyperproliferation of malignant CD4+ T cells with primary localization on the skin. The common characteristics are the migration of the malignant mature T‐lymphocytes into the epidermis, with hyperproliferation of malignant CD4+ T cells and epidermotropism. Sézary syndrome (SS) is the leukemic variant. It was established that CTCLs arise from a clonal expansion of CD4+ T cells with an identical rearrangement of the T cell receptor. The purpose of this study was to evaluate the immunomodulation effect of photochemotherapy‐A (psoralen plus ultraviolet A (PUVA)). Pre‐ and post‐PUVA punch skin biopsies of nine patients were stained immunohistochemically for CD34+, CD8+, CD7+, CD16+, CD56+, CD1a+, Bcl2+, p53+, CD45RA+, and CD45RO+ cells. The results showed a pre‐PUVA cells/mm² without significant difference among expansive or reactive cells. Post‐PUVA analysis showed a significant decrease in the mean of expansive‐reactive cells. PUVA immunomodulated decreasing cellular infiltrate. These findings could contribute to the comprehension of how PUVA acts. We achieved ectoscopic clearance of the lesions, although post‐PUVA, there still was a mononuclear pathological infiltrate. This result demonstrates that the PUVA treatment should only be withheld when the histological analysis is normal.     

CLL/SLL with initial presentation as a longstanding cutaneous plaque: a rare case

While chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in the western world, it uncommonly initially presents as a cutaneous lesion. When it does, it is often found incidentally in the context of another distinct lesion. We present a case of CLL/SLL that initially presented as a solitary nodular erythematous plaque on the left flank of a healthy 60‐year‐old man without lymphadenopathy or constitutional symptoms. The lesion had been present for many years, but had recently begun to grow and become pruritic and painful. Excisional biopsy revealed a large nodular aggregate of variably sized CD20(dim), CD5(+), CD23(+), BCL‐2(+) atypical lymphocytes in the dermis without epidermotropism. The lymphocytes were negative for BCL‐1/cyclinD1, BCL‐6, and CD10, and no other background lesion was identified. This constellation of biopsy findings was consistent with CLL/SLL. This case emphasizes the potential for involvement by CLL/SLL in the cutaneous biopsies of otherwise asymptomatic patients.     

Primary cutaneous marginal zone B-cell lymphoma: a clinical,histopathological, immunophenotypic and molecular genetic study of 22 cases

BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (MZCL) has recently been described. Differentiation from follicular centre cell lymphomas and lymphocytomas is often difficult due to insufficient experience and a lack of large series of patients. OBJECTIVES: To characterize primary cutaneous MZCL better, we report clinical, histopathological, immunophenotypic and molecular genetics features in a series of 22 patients. METHODS: All patients were treated and followed up at the same institution. Diagnosis of MZCL was based on the World Health Organization classification criteria. All samples were routinely tested with a wide panel of monoclonal antibodies. DNA was extracted from every sample following standard methods. IgH rearrangement and t(14;18)(q32;q21) studies were performed in all samples. RESULTS: Twenty-two patients (20 men, two women; mean age 50 years, range 24-77) were included. The mean follow-up was 43 months. Seventy per cent of patients presented with characteristic skin lesions on the trunk or extremities, consisting of deep red to violaceous infiltrated plaques, nodules or tumours frequently surrounded by diffuse or annular erythema. Four patients presented with lesions on the head and neck area. Two patients had disseminated skin lesions. The main histopathological features were non-epidermotropic, dense lymphocytic infiltrates mainly distributed in a nodular pattern. Adnexal involvement was usually present, with eventual formation of lymphoepithelial complexes. Cytologically, the infiltrate was polymorphous with marginal zone B cells and B-monocytoid cells. Blastoid CD30+ cells were often observed. Colonized reactive germinal centres and lymphoplasmocytoid differentiation were frequently present. Neoplastic cells were CD20+, CD79a+, CD5- and CD10-. Monotypic expression of light chains was observed in 18 cases (13 kappa; five lambda). Clonal IgH rearrangements were detected in 14 cases. The bcl-2 mutation t(14;18)(q32;q21) was demonstrated in two cases. Most patients were treated with local radiotherapy. Complete response rate with this approach was 100%. Six patients (27%) had skin recurrences from 6 months to 8 years after first treatment. Five patients (23%) had extracutaneous involvement. Two of them had a large cell transformation and one died of lymphoma. Three of four patients with head and neck presentation developed extracutaneous disease. CONCLUSIONS: MZCL appears to be a well recognizable entity, clinically, histologically and immunophenotypically. Although prognosis is generally good, the disease has potential for skin as well as extracutaneous recurrences. Large cell transformation and head and neck presentation may be associated with a worse prognosis.