Primary cutaneous anaplastic large‐cell lymphoma: a case report

Primary cutaneous anaplastic large‐cell lymphoma (PCALCL) is a part of the spectrum of CD30+ lymphoproliferative cutaneous processes. The characteristics include single or multifocal nodules that ulcerate as skin lesion, slow disease progression, autoregressive, and recurrent in few years. The present study report the case of a 16‐year‐old boy presenting PCALCL with single nodules, ulcer, keloid, and scab in his right‐side face. He showed a good response to the treatment with systemic chemotherapy and dermatoplasty, and regained confidence after the appearance of recovery. There is no relapse of the primary lesion and organs involved till now. The chemotherapy combining with surgical excision and dermatoplasty is a good method for PCALCL, per the lesion biopsy and positron emission tomography‐computed tomography before and after treatment.     

Primary cutaneous histiocyte and neutrophil-rich CD30+ and CD56+ anaplastic large-cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman

BACKGROUND: Cutaneous lymphomas co-expressing CD56 and CD30 are very rare. They share a clinicopathological overlap with natural killer- (NK)/T-cell lymphomas and anaplastic large-cell lymphomas (ALCLs), two entities with widely disparate clinical behavior. METHODS: We present a case of an immunocompetent 57-year-old Caucasian woman with a rapidly growing, angiodestructive and neuroinvasive primary cutaneous ALCL (PCALCL). The neoplastic population of large anaplastic CD30+ and CD56+ T cells was masked by a massive admixture of histiocytes and neutrophils. The partially ulcerated and pus-secreting tumor involved the forehead and scalp and was assessed as clinical stage IAE. RESULTS: After chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved a complete remission. Additionally, high-dose chemotherapy with autologous peripheral blood stem-cell transplantation was administered as a consolidation of complete remission, in which she has remained for 6 years. CONCLUSIONS: This is the first CD30+ and CD56+ primary skin lymphoma to be reported on the head. The presented case carries a remarkable combination of clinicopathological features of PCALCL and NK-/T-cell lymphoma.     

Primary cutaneous CD30+ anaplastic large-cell lymphoma with generalized skin involvement and involvement of one peripheral lymph node, successfully treated with low-dose oral etoposide

Primary cutaneous CD30+ anaplastic large-cell lymphoma (PCALCL) in adults is rare, and the prognosis is generally excellent. Multifocal PCALCL tends to relapse after multiagent chemotherapy and is generally considered more prone to progress to extracutaneous involvement than is the localized disease. We report a 43-year-old woman with PCALCL who had generalized skin involvement accompanied by involvement of one peripheral draining lymph-node region. Although the disease relapsed after multiagent chemotherapy regimens, the disease was successfully treated with low-dose etoposide. We reviewed the previously reported cases of PCALCL treated with low-dose etoposide. We suggest that oral etoposide might be a useful effective treatment for treatment of relapsed multifocal PCALCL.     

Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders

BACKGROUND: Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. OBJECTIVES: To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES. METHODS: Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30. RESULTS: CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder. CONCLUSIONS: We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.     

Human herpesvirus type 8 and Epstein–Barr virus-associated cutaneous lymphoma taking anaplastic large cell morphology in a man with HIV infection

Human herpesvirus type 8 (HHV-8, Kaposi's sarcoma-associated herpesvirus)-positive lymphoma taking anaplastic large cell morphology in the skin is described in a 46-year-old man with AIDS. Multiple erythematous nodules appeared on the trunk and extremities during the treatment of AIDS. Histological examination of cutaneous nodules showed dense infiltration of CD30 + atypical lymphoid cells in the deep dermis. Immunoglobulin JH gene rearrangement was detected in these lymphoma cells. Both Epstein-Barr virus-encoded small RNA and HHV-8 mRNA (T1.1/nut-1) were detected in these lymphoma cells by in situ hybridization. Remarkable retention of the pericardial fluid was observed at the same time that cutaneous lesions grew, and lymphoma cells in the pericardial fluid showed the same phenotype as the cutaneous lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone effectively reduced both the cutaneous nodules and pericardial fluid. However, the patient died 4 months after diagnosis because of cytomegalovirus infection. As far as we know, this is the first report of an HHV-8-positive cutaneous lymphoma taking anaplastic large cell morphology. This case suggests the association of AIDS-related anaplastic large cell lymphoma with HHV-8.     

CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma

BACKGROUND: CD30+ cutaneous lymphoproliferative disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have an excellent prognosis. OBJECTIVE: We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30+CLPDs. METHODS: A retrospective cohort analysis of 56 patients with CD30+CLPDs treated at our institution was performed. RESULTS: No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL. CONCLUSION: Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.     

Solitary primary cutaneous CD30+ large cell lymphoma of natural killer cell phenotype bearing the t(2;5)(p23;q35) translocation and presenting in a child

Primary cutaneous CD30+ large cell lymphoma is an unusual tumor most commonly seen in adults. Most of these lymphomas are of T-cell origin and carry a good prognosis. We present the case of a 4-year-old girl with stage IEA CD30+ large cell lymphoma with a CD56+ natural killer cell phenotype and the t(2;5)(p23;q35) translocation. After excision, the patient has been free of disease for 44 months. Primary cutaneous CD30+ large cell lymphoma is uncommon in children. To our knowledge, primary cutaneous CD30+ natural killer type lymphoma has not been reported previously. The indolent behavior of this tumor indicates its similarity to other primary cutaneous CD30+ large cell lymphomas and its difference from other CD56+ lymphomas involving the skin, which often exhibit an aggressive clinical course. Cases such as this one illustrate why the use of a single, or even a few, immunohistochemical stains can be misleading in regard to lymphoma classification and prognostication.     

Primary cutaneous follicle center lymphoma with Hodgkin and Reed‐Sternberg‐like cells: a new histopathologic variant

Primary cutaneous follicle center lymphoma (PCFCL) is the most frequent cutaneous B‐cell lymphoma. A 62‐year‐old man presented with a solitary indolent subcutaneous nodule for 3 years duration, without other abnormalities. Histological examination showed lymphoproliferation with a nodular growth pattern characterized by fibrous collagen bands surrounding nodules. The nodules were composed of medium‐sized centrocytes admixed with many large multilobulated and lacunar cells without eosinophils or granulomatous aspect. Hodgkin‐like cells were CD30+, CD15+, PAX5+, OCT2+, BOB1+, MUM1+, Ki67+, Bcl6+ and focally CD20+ and EMA?, CD79a?, Bcl2? and CD10?. The medium‐sized cells were CD20+, CD79a+, Bcl2+, Bcl6+ and CD10+, enmeshed in a network of CD21‐positive follicular dendritic cells. Epstein‐Barr virus detection was negative. Interphase fluorescence in situ hybridization showed the absence of BCL2 or BCL6 rearrangement. In such a case, the presence of Hodgkin‐like cells intermixed with the tumor population may result in a pitfall diagnosis of classical Hodgkin lymphoma (CHL). Differential diagnoses to be ruled out are secondary or primary skin localization of rather CHL, or systemic follicular lymphoma. Several clinical, radiological, histological, immunohistochemical and molecular arguments indicated the diagnosis of PCFCL. To our knowledge, this is the first report of PCFCL with Hodgkin‐like cells.     

Primary Cutaneous CD8+ CD30+ Anaplastic Large Cell Lymphoma: An Unusual Case with a High Ki-67 index—A Short Review

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a part of the spectrum of CD30⁺ cutaneous lymphoproliferative disorder, characterized by variable degrees of CD2, CD3, CD4 and CD5 expression by lymphoid cells. PCALCLs with an expression of cytotoxic phenotype (CD8⁺) and cytotoxic proteins are uncommon. Cutaneous CD8⁺ CD30⁺ lymphoproliferative lesions are difficult to classify, diagnose and may be the cause of misdiagnose. CD8⁺ PCALCL must be distinguished from CD8⁺ mycosis fungoides, lymphomatoid papulosis type D and primary cutaneous aggressive epidermotropic CD8⁺ T-cell lymphoma. Usually CD8⁺ PCALCL is an indolent disease with a favorable prognosis, except few cases can show poor outcomes. The high Ki-67 index points toward advanced PCALCL. Treatment modalities include surgical excision, radiotherapy and clinical monitoring. Chemotherapy is reserved for disseminated disease. We report a 59-year-old male presented with rapid development of multiple painful reddish-brown plaques and nodular ulcerative skin lesions over the left thigh region since 2 months. A diagnosis of CD8⁺ PCALCL with a high Ki-67 index was made on the basis of histology and immunohistochemistry, in co-relation with clinical presentation.     

A case of systemic anaplastic large cell lymphoma with ‘Hodgkin‐like’ appearance and skin involvement mimicking lymphomatoid papulosis

We report a unique case of the CD30+ anaplastic large cell lymphoma (ALCL). A 44‐year‐old Japanese male presented with lymphadenopathy followed by skin involvement. Initially, a swollen cervical lymph node was recognized in 1989 and relapsed in 1991, which was histologically diagnosed as Hodgkin disease of nodular sclerotic type. In 1996, he presented ulcerative cutaneous nodules and swollen lymph nodes in his left inguinal region, which was then diagnosed with CD30+ ALCL. Both the lymphadenopathy and the skin lesion had been completely remitted by combining chemotherapy followed by radiotherapy. Thereafter, he had relapsing and remitting episodes of multiple papules and nodules on his face, trunk and extremities for 10 years. Repeated histopathological examination revealed similar tumor cell proliferation in the papules/nodules of the skin. Essentially similar immunohistochemical features, including CD30 and granzyme B expression, but not anaplastic lymphoma kinase (ALK), strongly suggested that all these tumors were sequential expression of one disease continued for 19 years. This case was finally diagnosed as CD30+ ALCL with unique skin involvement mimicking lymphomatoid papulosis (LyP). Kiniwa Y, Ide Y, Fukushima M, Asano N, Saida T. A case of systemic anaplastic large cell lymphoma with ‘Hodgkin‐like’ appearance and skin involvement mimicking lymphomatoid papulosis.     

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.     

Localized perineal cutaneous nodules: a case of recurrent systemic anaplastic large‐cell lymphoma

We report an unusual case of localized cutaneous nodules heralding the recurrence of systemic CD30+ anaplastic large‐cell lymphoma (ALCL). A 47‐year‐old woman developed numerous violaceous nodules in the perineal and upper thigh area 3 years after multimodal treatment and complete remission of primary anaplastic large‐cell CD30+ lymphoma. Using immunohistochemical and T‐cell gene rearrangement analysis, a recurrence of her anaplastic large‐cell lymphoma was diagnosed.     

Anaplastic large-cell T-cell lymphoma

A 64-year-old woman presented with 2 years of pruritic and ulcerated nodules and tumors on the trunk and arms. Histopathologic examination showed a diffuse infiltrate that consisted of predominantly small lymphocytes and scattered large atypical multinucleated cells positive for CD30. These findings were consistent with a diagnosis of anaplastic large-cell T-cell lymphoma, which is a CD30+ cutaneous lymphoma. This case highlights the importance of considering both histopathologic and clinical criteria in diagnosing a patient with a CD30+ cutaneous lymphoma.     

Primary cutaneous CD30-positive large cell lymphoma

Primary cutaneous CD30-positive large cell lymphoma is a recently described entity, recognized by immunohistochemical criteria. Spontaneous regression may occur and although relapses are frequent, most patients have a favourable prognosis. We describe a 83-year-old woman with a large ulcerated tumour on her right forearm, with 2 months evolution. Histological and immunohistochemical examination revealed a CD30-positive large cell lymphoma. Systemic involvement was not detected. The tumour regressed spontaneously. Cutaneous relapses occurred one year later, all with spontaneous regression. After a 2-year follow-up period, the patient is well, without concurrent extracutaneous disease. This case is in keeping with other reports of spontaneous regression and favourable outcome of this type of cutaneous lymphoma.     

CD56 expression in a case of primary cutaneous CD30+ anaplastic large cell lymphoma

We describe clinicopathological features of an unusual case of CD30+/CD56+ T-cell lymphoma in a 58-year-old Korean man who presented with disseminated nodules, papules and hyperpigmented patches. Coexpression of CD30 and CD56 in T-cell lymphoma is very rare. Our patient did not respond to an intensive chemotherapy regimen, in contrast to the previously reported cases of primary cutaneous CD30+ anaplastic large cell lymphoma. Coexpression of CD56 might therefore identify a subset of CD30+ lymphomas with more aggressive features.     

Primary CD30+ve cutaneous T-cell lymphoma associated with chronic burn injury in a patient with longstanding psoriasis

An increased incidence of lymphoma has been reported in psoriatic patients, but most cases are nodal B-cell lymphoma. We report a unique case of CD30-expressing cutaneous T-cell lymphoma arising from underlying psoriatic plaque after intractable caustic burns and cellulitis in the palm of a patient with generalized chronic plaque psoriasis. Molecular studies confirmed a localized clonal T-cell expansion, and the lesion responded dramatically to multiagent chemotherapy. The case highlighted the possible role of chronic systemic and local T-cell activation in the pathogenesis of primary CD30+ve cutaneous T-cell lymphoma, and the importance of histologic assessment in chronic nonhealing skin lesions.     

Gene expression profile in a case of primary cutaneous CD30-negative large T-cell lymphoma with a blastic phenotype

A 65-year-old Japanese woman presented with disseminated erythematous patches, plaques, and nodules on the trunk and limbs. Histological examination showed diffuse and dense infiltrates located in the dermis and subcutis, composed of large pleomorphic T lymphocytes. Immunohistochemically, neoplastic cells were positive for blastic T-cell markers, but negative for CD30 (Ki-1) antigen. Based on the clinicopathological findings, a diagnosis of primary cutaneous large T-cell lymphoma was made. Despite systemic chemotherapy, the patient died 7 months after diagnosis. Gene expression profiling using complementary DNA microarrays indicated significantly increased expression of an apoptosis-inhibitory protein and certain cyokines and cytokine receptors (e.g. MCP-1, MCP-2, IP-10, and IL-2R gamma) in the tumour-indurated skin. Comprehensive gene expression patterning in additional cases may provide useful information regarding the biological and clinical behaviour of aggressive cutaneous lymphomas such as CD30-negative large T-cell lymphoma.     

Primary cutaneous anaplastic large cell lymphoma with intralymphatic involvement associated with chronic lymphedema

Chronic lymphedema predisposes to develop malignant cutaneous tumors, including angiosarcoma, Kaposi's sarcoma and B‐cell lymphoma. T‐cell malignancy has rarely been associated with chronic lymph stasis. Here, we report a case of primary cutaneous anaplastic large cell lymphoma (pcALCL) with lymphatic spread associated with chronic lymphedema. The patient is a 56‐year‐old man who received orchiectomy and right inguinal lymphadenectomy for malignant seminoma 10 years ago, which led to prominent lymphedema of the right leg. He developed extensive skin nodules on the lymphedematous area for 3 months. Histopathology findings confirmed a diagnosis of pcALCL, which is a subtype of cutaneous T‐cell lymphoma characterized by the presence of CD30+ T cells. Intralymphatic infiltration of malignant cells is prominent. The pathogenesis of intralymphatic cutaneous anaplastic large cell lymphoma is largely unknown. Our case suggests that chronic lymphedema resulted in persistent CD4+ T‐cell inflammation, which then may contribute to the development of pcALCL.     

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.     

CD8-positives,CD30-negatives kutanes T-Zell-Lymphom unter dem klinischen Bild eines Pyoderma gangraenosum

Ulcerated primary cutaneous lymphomas are not rare, but the clinical manifestation as a pyoderma gangrenosum look-alike is extraordinary. CD8-positive lymphomas are rare, unclassifiable tumours with variable prognosis. We report on a 49-year-old patient with a large ulcerated primary cutaneous lymphoma on the left chest wall presenting as pyoderma gangrenosum. With immunohistochemical staining, most lymphocytes were shown to be CD8-positive. The CD30 antigen was not expressed. After radiotherapy with complete skin irradiation, the lymphoma regressed completely. The patient has been free of relapse for 28 months so far.