Cutaneous involvement by colonic extranodal NK/T-cell lymphoma mimicking mycosis fungoides: a case report*

We report a 51-year-old woman with cutaneous involvement by extranodal NK/T-cell lymphoma (TCL) of the colon that microscopically mimicked mycosis fungoides (MF). She had a history of fever of unknown origin for 2 months and then developed multiple erythematous papules on her trunk and extremities. A skin biopsy revealed superficial infiltration by atypical small to medium-sized lymphocytes with epidermotropism and Pautrier collections. Immunohistochemical studies showed expression of CD3 and TIA-1 with lack of expression (double negative) of CD4 and CD8. Initially, we reported the diagnosis as MF, cytotoxic variant. Thereafter, computerized tomography scan incidentally identified a colonic mass. A colonic biopsy revealed infiltration of atypical lymphoid cells with the same morphology and immunophenotype as those found in the skin. Additionally, CD56 and Epstein-Barr virus-encoded RNA in situ hybridization in both skin and colonic biopsies were diffusely positive. Thus, extranodal NK/TCL was diagnosed. Delta T-cell receptor (TCR) gene rearrangement was documented in the skin biopsy by polyacrylamide gel electrophoresis and fluorescence capillary gel electrophoresis methods. There was no TCR gene rearrangement detected in the colonic biopsy. Unfortunately, the patient died within 2 months of diagnosis.     

结外鼻型NK/T细胞淋巴瘤

报告1例结外鼻型NK／F细胞淋巴瘤。患者男，43岁。左面部红肿1个月余。初发时表现为左下眼睑红肿，以后红肿范围渐扩大，累及整个左侧面部，并有水疱形成甚至破溃。根据皮损组织病理检查和免疫组化染色结果，确诊为结外鼻型NK／T细胞淋巴瘤。     

Cutaneous extranodal NK/T‐cell lymphoma mimicking cellulitis an HIV positive patient without lymphopenia

We present the case of a 28‐year‐old male with a history of human immunodeficiency virus (HIV) with a 1‐month history of a steadily enlarging, firm painful lesion on the right posterior shoulder. The patient was initially treated for cellulitis given his clinical picture. Histopathologic examination revealed an angiocentric and dermal proliferation of markedly atypical lymphoid cells with numerous mitoses and apoptotic bodies along with broad zones of necrosis. Biopsy revealed the presentation to be consistent with NK/T‐cell lymphoma. The cutaneous lesions from NK/T‐cell lymphoma can often be initially mistaken for cellulitis, therefore this malignancy should be included on the differential in a patient HIV/acquired immune deficiency syndrome (AIDS).     

鼻NK/T细胞淋巴瘤1例

报道1例以皮肤为首发症状的鼻NK／T细胞淋巴瘤。患者男，48岁。双下肢、躯干、双上肢陆续出现红色斑丘疹、结节及溃疡4月余，鼻腔发现新生物1月余。皮肤及鼻部组织病理示中、小淋巴样细胞弥漫浸润；免疫组化染色：CD56（＋），LCA（＋），UCLH－1（＋），26(-),CD57(-);EBER( )。     

Nasal natural killer/T cell lymphoma with cutaneous involvement: case report and Chinese literature review reported in China mainland

Nasal natural killer (NK)/T cell lymphoma is an Epstein-Barr virus (EBV) associated lymphoma that arises in the nasal area and aggressively invades surrounding tissues. Our patient was a 48-year-old male who had had nasal obstruction and nasal discharge for 2 years and infiltrating plaques and necrosis on his nasal dorsum for three months. He developed fever and fatigue two weeks before admission. Biopsy from both skin and nasal mucosa revealed atypical medium-sized tumor cells infiltrating into the dermis. Immunohistochemical studies revealed that the tumor cells were UCHL-1, cytoplasmic CD3, CD56, TIA-1, and granzyme B positive, and CD8 and CD20 negative. In situ hybridization for EBV-DNA was positive. Clonal TCRb and TCRg gene rearrangement were negative. The patient was treated with cyclophosphamide, vincristine, and prednisone (COP) and with local radiotherapy, but he died 20 days later. We reviewed the cases of nasal NK/T cell lymphoma reported in mainland China in the Chinese literature during the last 5 years.     

鼻部NK/T细胞淋巴瘤累及皮肤

为了探讨鼻部NK／T细胞淋巴瘤累及皮肤的临床表现、病理、免疫表型及EB病毒相关性。通过临床表现及病程，分析原发及累及部位。通过UCHL－1，CD56,多克隆CD3，CD8，CD20，TIA－1，粒酶B（GrB）等对肿瘤细胞免疫表型进行研究，EBV－EBER探针原位杂交检测肿瘤细胞阳性率分析其病因及发病。结果本例皮肤及鼻部取材组织病理表现为坏死及中等大小的异型性肿瘤细胞增生浸润，UCHL－1＋，CD56＋，CD3＋，CD8－，CD20－，TIA－1＋，granzyme B ,为NK／T细胞淋巴瘤表型。EBV瘤细胞阳性率达60％，进一步证实为鼻部NK／T细胞淋巴瘤，EBV相关性。支持鼻部NK／T细胞淋巴瘤是具有特殊免疫表型，与EB病毒有高度相关性的独立疾病，临床进展迅速，病程短，提示为高度侵袭性。     

TCR gene-rearranged,extranodal NK/T-cell lymphoma,nasal type,presenting as gyrate patches

In the CD56+ cutaneous nasal-type NK/T-cell lymphoma strongly associated with latent EBV infection, subcutaneous or dermal nodules are the most common skin findings, but great morphologic heterogeneity has been noted including papules, infiltrated plaques, and ulcerated tumors, and TCR genes are mostly germline. We describe a case of nasal and nasal-type NK/T-cell lymphoma featuring multiple erythematous polycyclic patches on the trunk, which is similar to patch stage mycosis fungoides or other cutaneous T cell lymphoma. Immunohistochemical study of a skin biopsy specimen revealed CD2+, CD3epsilon+, CD56+, and CD45RO+ expression in the neoplastic cells. In situ hybridization using an anti-sense Epstein Barr virus early regions probe showed a positive reaction. However, clonal TCR beta gene rearrangement was found.     

Lethal T- and NK-cell lymphomas mimicking granulomatous panniculitidies: a clinicopathologic study of three cases

An infiltrate mimicking subcutaneous panniculitis associated with a granulomatous response represents an uncommon histopathologic presentation of lymphoma. We report three cases, comprising one case each of nasal-type extranodal NK/T-cell lymphoma, cutaneous γ/δ T-cell lymphoma and human T-lymphotropic virus-I associated adult T-cell leukemia/lymphoma, which based on initial histopathologic and/or clinical presentation were thought to represent systemic lupus erythematosus, sarcoidosis and psoriasiform dermatitis, respectively. Excisional biopsies of indurated lesions performed at our institute; however, in each case showed an atypical subcutaneous lymphohistiocytic infiltrate associated with a variable number of granulomas. Extensive immunophenotypic characterization, in conjunction with histomorphologic and molecular analysis, established the diagnosis of lymphoma in all instances. All patients had a rapidly progressive clinical course and death was attributable to complications of lymphoma shortly after diagnosis. These cases highlight the importance of using a multimodality diagnostic approach to distinguish lymphomas masquerading as granulomatous panniculitis from inflammatory or reactive disorders associated with such histopathologic patterns.     

伴全身弥漫性红斑的结外NK/T细胞淋巴瘤1例

患者女,26岁。反复出现发热、皮下结节和红斑半年,全身红斑水肿加重半月。皮肤组织病理示:表皮细胞有变性坏死,基底细胞液化变性,真皮浅层较多慢性炎症细胞浸润,皮下脂肪局部变性。鼻中甲黏膜活检示:黏膜间质淋巴细胞异型增生,核大扭曲;LCA+,CD3+,UCHL-1+,CD4-,CD8+,CD56+,TIA+,GranzymeB+。诊断:结外NK/T细胞淋巴瘤。全身弥漫性水肿性红斑,皮下结节损害是一种副肿瘤综合症的表现,对患者全面筛查有助于早期发现潜在恶性肿瘤。     

鼻型节外NK/T细胞淋巴瘤1例

患者女,46岁。双下肢相继出现红色结节及溃疡4月余,鼻部溃疡1个月。右大腿皮损组织病理示:大淋巴样细胞弥漫浸润;免疫组化染色:CD2,CD3,CD56,TIA-1,Grb和EBER均(+),CD20(-)。诊断:鼻型节外NK/T细胞淋巴瘤。     

Skin is the frequent site for involvement of peripheral T-cell and natural killer cell lymphomas in Korea

We have studied the clinicopathological features of 19 Korean cases of peripheral T-cell and natural killer (NK) cell lymphomas, not including mycosis fungoides. Primary cutaneous involvement was demonstrated in eight of these 19 cases, and we recognized four clinicopathologic subtypes among these eight patients: nasal type NK/T cell lymphoma, three cases; primary cutaneous CD30 positive anaplastic large cell lymphoma, two cases; subcutaneous panniculitis-like T-cell lymphoma, one case; lymphoma with hydroa vacciniforme-like cutaneous lesions, two cases. We did not, however, encounter any cases of HTLV-associated adult T-cell lymphoma/leukemia, which is common in Taiwan and Japan. EBV-associated lymphoma is the most prominent type of peripheral T-cell and NK cell neoplasm involving the skin in Korea.     

皮肤血管内T细胞淋巴瘤一例

患者女,64岁,6个月前全身出现多发淡红色斑丘疹,质硬,直径1～3 cm,以左侧颜面部及双下肢明显.曾就诊于某医院,诊断为血管炎.1个月前出现头痛、头晕伴步态不稳,同时伴双手及左足麻木、视物模糊,行头颅CT检查提示"右侧额辐射区腔隙性脑梗塞",1个月来步态不稳逐渐加重,再次就诊于当地医院,行头颅MRI检查提示"双侧丘脑、右侧基底节、右侧额叶及右侧小脑半球梗塞,左侧蝶窦旁异常信号灶".患者为进一步诊治于2010年1月至本院治疗,门诊拟诊脑梗死收住入院.皮疹予复方倍他米松注射液、冰黄肤乐软膏等治疗后稍见好转.     

累及皮肤的结外鼻型NK/T细胞淋巴瘤

报告1例累及皮肤的结外鼻型NK/T细胞淋巴瘤.患者男,72岁.确诊结外鼻型NK/T细胞淋巴瘤8年后,鼻根部出现红肿、破溃.根据皮损、组织病理检查和免疫组化染色结果确诊.     

CD20‐Positive nodal natural killer/T‐cell lymphoma with cutaneous involvement

CD20‐positive natural killer (NK)/T‐cell lymphoma is extremely rare. We describe a case of a CD20‐positive nodal NK/T‐cell lymphoma with cutaneous involvement in a 32‐year‐old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA‐1 and CD20 but negative staining for other B‐cell markers, including CD79a and PAX‐5 and T‐cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein–Barr virus‐encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T‐ and B‐cells.     

Intravascular large B-cell lymphoma of the cutaneous variant in Korea

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. It is characterized by proliferation of malignant lymphoid cells within the small vessels of various organs. The skin and central nervous system are commonly involved although it occurs in other organs such as the kidneys, adrenals, lung and liver. In Western patients, there is a cutaneous variant of IVLBCL, which involves only the skin. However, the Asian variant, which rarely involves the skin, is associated with hemophagocytosis. It was reported in the majority of Japanese patients. Here, we report a case of the cutaneous variant of IVLBCL in a Korean individual.     

Angiotropic B-cell lymphoma with telangiectasia, accompanied by panniculitic formation

A 67-year-old female presented with diffuse edema, generalized telangiectasia, and indurated skin plaques. Histopathological findings of the skin lesion included CD45+/CD79+/CD20+ large lymphoma cells that filled the vascular lumina and infiltrated the subcutaneous tissues with panniculitic formations. Three cycles of a CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) chemotherapy regimen resolved the skin manifestations. After five cycles of CHOP, however, she developed dementia-like symptoms. Three cycles of additional intrathecal chemotherapy (methotrexate, cytarabine and prednisolone) did not improve the neurological symptoms.     

Relapsed hepatosplenic T-cell lymphoma heralded by a solitary skin nodule

Hepatosplenic T-cell lymphoma (HSTL) represents a rare form of peripheral T-cell lymphoma composed of lymphocytes that typically express the γδ T-cell receptor. This form of lymphoma rarely involves the skin. We report the case of a 23-year-old man with a history of HSTL that was presumed to be in remission who presented with a solitary cutaneous nodule. Skin biopsy showed an atypical lymphocytic infiltrate arranged in a perivascular and periappendageal pattern with associated vacuolar epidermal interface change. The constituent T cells expressed CD2, CD3, CD7, CD8, β-F1, γδ T-cell receptor, Tia-1 and granzyme B. The cells lacked the expression of CD4, CD5 and CD56. Fluorescence in situ hybridization (FISH) showed a characteristic chromosomal abnormality, namely isochromosome 7q, which confirmed the diagnosis of cutaneous HSTL. On restaging his disease, widespread progression was noted. To our knowledge, this report provides the first detailed account of cutaneous involvement by HSTL. We show the novel utility of FISH to identify isochromosome 7q in the lesional skin of HSTL patients.     

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.