Epidermotropic precursor T-cell lymphoma with highly aggressive clinical behavior simulating localized pagetoid reticulosis

We describe a 43-year-old patient with a solitary, eczematous plaque on his right nipple that had developed during the previous 6 weeks. Histopathology revealed a superficial band-like infiltrate of medium to large-sized pleomorphic lymphocytes with striking epidermotropism. The tumor cells expressed a T-phenotype (CD3+, CD20-) and were CD30-, CD4-, and CD8-negative. A diagnosis of localized pagetoid reticulosis (Woringer-Kolopp disease) with possible large cell transformation was proposed. A cervical lymph node excised 2 months later showed features of a highly aggressive blastoid precursor T-cell lymphoma. Reevaluation of the skin lesion and of a tonsil specimen previously interpreted as benign hyperplasia showed features consistent with those observed in the lymph node. The disease was rapidly progressive, and the patient died 15 months after the first skin biopsy. This case represents a unique cutaneous presentation of aggressive precursor lymphoma, showing the protean nature of lymphoproliferative disorders and the overlapping clinical and histopathologic features of different entities.     

Brainstem involvement by mycosis fungoides in a patient with large-cell transformation: a case report and review of literature

BACKGROUND: Central nervous system (CNS) involvement by mycosis fungoides (MF) is rare. As compared to meningeal involvement, intraparenchymal spread is especially rare. It is usually seen in advanced disease in conjunction with lymph node or visceral involvement. However, CNS involvement in the absence of progressive skin lesions or other extracutaneous involvement has been reported rarely in patients with transformed MF. METHOD: Case report and review of literature. RESULTS: A 71-year-old female with long-standing MF developed lymphomatous CNS involvement 10 years after the diagnosis of tumor stage MF. At this time, the patient presented with a transient episode of garbled speech followed by generalized weakness. Computerized tomography scan (CT scan) and magnetic resonance imaging scan (MRI scan) of the head revealed a subcortical lesion in the left temporo-frontal lobe. Cerebrospinal fluid (CSF) examination showed atypical T cells, and brain biopsy confirmed parenchymal involvement by T-cell lymphoma. Meanwhile, a biopsy of a skin lesion showed large-cell transformation. No lymph node or other systemic involvement was noted at this time, and the patient was treated with chemotherapy. Twelve months later, the patient developed recurrent CNS lymphoma with multiple organ involvement and expired soon thereafter. CONCLUSIONS: This case illustrates the importance of awareness of the possibility of CNS involvement by MF, especially in transformed MF. CNS involvement may be the only site of extracutaneous involvement in patients with transformed MF, and mental status changes warrant CNS surveillance for this disease.     

KSHV/HHV8-associated primary cutaneous plasmablastic lymphoma in a patient with Castleman's disease and Kaposi's sarcoma

Abstract:  We report a unique case of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV)/human herpesvirus (HHV)8-associated lymphoma in a 56-year-old man with a history of acquired immune deficiency syndrome, Castleman's disease, KS, and idiopathic thrombocytopenic purpura. Three months following the diagnosis of KS affecting a left cervical lymph node and Castleman's disease with bone marrow involvement, he presented with a subcutaneous, tender lesion on his left arm. A skin biopsy demonstrated a superficial and deep, interstitial-nodular infiltrate of severely atypical lymphoid cells showing plasmacytoid features, numerous mitotic figures, and frequent individual apoptotic tumor cells. The morphologic features were those of plasmablastic lymphoma (PBL). Immunohistochemical study showed that the lymphoma cells strongly expressed CD45, CD30, and KSHV/HHV8 latency-associated nuclear antigen. KSHV/HHV8 was also detected in the biopsy sections of the patient's KS and Castleman's disease. Epstein–Barr virus in situ hybridization was diffusely positive. In situ hybridization demonstrated κ-light chain restriction. Although KSHV/HHV8 has been individually associated with KS, Castleman's disease, and PBL, this appears to be the first reported case in which all three entities were present simultaneously in one person, suggesting a critical role of KSHV/HHV8 as a common denominator in the pathogenesis of these diseases.     

Dermatitis herpetiformis in a Japanese patient with anaplastic large cell lymphoma

We report a 73-year-old Japanese man with dermatitis herpetiformis which developed after diagnosis of anaplastic large cell lymphoma. The patient suffered fever, sweating, shivering, and multiple enlarged cervical lymph nodes. The diagnosis of anaplastic large cell lymphoma was confirmed by the histologic features of a biopsied cervical lymph node. The patient underwent combination chemotherapy. However, one month after the initial therapy, pruritic erythematous skin lesions with peripheral vesicles appeared on his buttocks. A skin biopsy showed subepidermal blister formation associated with polymorphonuclear and mononuclear cell infiltrates. Direct immunofluorescence examination of the area adjacent to the lesion showed granular deposits of IgA at the dermoepidermal junction. While it is well-known that dermatitis herpetiformis can develop into lymphoma, there have been only a few reports of its appearance after a diagnosis of lymphoma. This case suggests that dermatitis herpetiformis may be induced by anaplastic large cell lymphoma.     

Development of Ki-1 lymphoma in a child suffering from multicentric reticulohistiocytosis.

We report a case of Ki-1 lymphoma that developed in a 16-year-old youth who had suffered from multicentric reticulohistiocytosis for 10 years. Over the past 3 years he had had a peculiar sclerosing lesion of the leg for which oral prednisone 5 mg daily was tried for one year, with a moderate effect. He developed a marked swelling of the inguinal lymphadenopathy on the same side as the affected leg lesion, which also developed a prominent swelling of the skin surrounding the sclerosed area. Immunohistochemical analysis of the lymph node biopsy revealed the features of Ki-1 lymphoma. This is the first case of association of multicentric reticulohistiocytosis with Ki-1 lymphoma.     

Cutaneous lesions as the first manifestation of systemic follicular lymphoma in an HIV patient

Human immunodeficiency virus (HIV) patients have an increased incidence of lymphomas, particularly when there is a significant immunosuppression. Most commonly, they are non-Hodgkin B cell type with a high or intermediate grade and have an extranodal presentation. We report the case of a 38-year-old man with HIV infection who presented with a 1-year history of a painless tumor on the back and lymphadenopathies. The diagnosis of B cell lymphoma follicle center cell type was established by skin biopsy. Staging included a bone marrow biopsy revealing infiltration by the lymphoma and a whole-body computed tomographic scan showing multiple cervical and axillary lymphadenopathies with necrotic center. Biopsy of an axillary lymph node revealed caseating epithelioid granulomas and Ziehl-Neelson staining was positive for acid-fast bacilli. The patient started therapy for tuberculosis and polychemotherapy for lymphoma with complete response. This report illustrates a case of simultaneous occurrence of tuberculosis and systemic follicular lymphoma presenting in skin in an HIV patient.     

以皮肤损害为首发症状的鼻型NK/T细胞淋巴瘤1例

报告1例以皮肤损害为首发症状的鼻型NK／T细胞淋巴瘤。患者男,29岁。四肢、躯干相继发生多个皮下结节、肿块及无痛性深部溃疡10个月余,鼻塞、眼睑高度肿胀伴高热半个月余。皮疹、鼻部组织及淋巴结组织病理示,肿瘤细胞核不规则．伴大片坏死,可见血管壁浸润,并见吞噬核碎片。免疫组化染色结果示,CD56( ),CD45R0( ),CD3( ),gmnzymeB( ),CD20(-)。     

A case of cutaneous clear cell sarcoma determined by clinicopathological and cytogenetic analysis

Cutaneous clear cell sarcoma (CCS) is a rare soft tissue malignancy that typically manifests in the distal extremities of young adults. Although it shows melanocytic differentiation, CCS is clearly pathologically and genetically distinct from malignant melanoma. Here, we report the case of a 43-year-old male who had an asymptomatic, deep-seated, slowly enlarging, firm mass over the right heel for 30 years that recently and rapidly progressed with tenderness. We arranged for the total excision of the tumor. Pathological and cytogenetic analysis of the biopsied specimen showed that it was a clear cell sarcoma. Computed tomography and positron emission tomography scans showed no signs of metastasis, and no other abnormal hypermetabolic lesions were detected. Wide excision with split-thickness skin graft and a sentinel lymph node biopsy were performed. Because of positive findings in the sentinel lymph nodes, the patient was transferred to the plastic surgery department for further radical popliteal and inguinal lymph node dissection. The patient has received regular outpatient follow-up care in our hospital for the past 8 months with no evidence of recurrence.     

Paraneoplastic pemphigus associated with non-Hodgkin lymphoma

We report a case of a 55-year-old man who, after a 6-month history of enlargement of cervical lymph nodes, presented with multiple painful ulcerations of the oral mucosa and lips and multiple skin erosions on the trunk, back, extremities, and genitals. A lymph node biopsy was performed and revealed diffuse peripheral B-cell non-Hodgkin lymphoma. Skin biopsy revealed an acantholytic blister in the epidermis. Direct immunofluorescence showed IgG deposition in the intercellular spaces of the epidermis and linear C3 deposition in the basement-membrane zone. The indirect immunofluorescence test on rat urinary bladder epithelium was positive with a 1:320 titre. Paraneoplastic pemphigus was diagnosed based on these findings; treatment was started with cyclophosphamide, doxorubicin, vincristin and prednisone. The patient's response to treatment was poor and he developed several complications and died 2 months after diagnosis.     

Cutaneous clear cell sarcoma: report of three cases of a potentially underestimated mimicker of spindle cell melanoma

Clear cell sarcoma is a unique soft tissue tumor with distinct microscopic features that include a nested or fascicular pattern of spindle cells accompanied by larger wreath-like giant cells scattered throughout. It harbors a unique EWSR1-ATF1 gene fusion secondary to a t(12;22)(q13;q12) translocation. Recently, it was reported that clear cell sarcoma can occur in the skin and mimic a broad spectrum of entities, including spindle cell melanoma. Here, we describe 3 new cases of clear cell sarcoma of the skin, all of which were confirmed molecularly. The patients, a 12-year-old boy, a 29-year-old woman, and a 60-year-old man, had cutaneous lesions on the thigh, dorsum of foot, and sole, respectively. All 3 lesions were originally considered suspicious of spindle cell melanoma. Microscopically, the lesions featured nodular proliferation centered in the dermis that consisted of discrete fascicles of spindle cell enmeshed by thin fibrous strands. Wreath-like cells were present in all cases. Tumor cells were positive for S100 protein (3 of 3 cases), melan A (2 of 3 cases), HMB 45 (1 of 3 cases) although a junctional melanocytic proliferation was seen in 1 case. Sentinel lymph node biopsy was negative in 2 patients. Follow-up was uneventful in 2 patients, whereas the other patient developed a lymph node metastasis 5 months after primary tumor excision. This study confirms that malignant dermal tumors that mimic but do not exactly replicate spindle cell melanoma should raise suspicion for cutaneous clear cell sarcoma and prompt the investigation for the confirmatory gene fusion t(12;22).     

Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma

Primary effusion lymphoma (PEL) is a rare and aggressive lymphoma that arises in the context of immunosuppression and is characterized by co‐infection with Epstein–Barr virus (EBV) and human herpesvirus‐8/Kaposi sarcoma‐associated herpesvirus (HHV‐8/KSHV). It was originally described as arising in body cavity effusions, but presentation as a mass lesion (extracavitary PEL) is now recognized. Here, we describe a case of PEL with an initial presentation as an intravascular lymphoma with associated skin lesions. The patient was a 53‐year‐old man with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who presented with fevers, weight loss and skin lesions concerning for Kaposi sarcoma (KS). A skin biopsy revealed no evidence of KS; however, dermal vessels contained large atypical cells that expressed CD31 and plasma cell markers but lacked most B‐ and T‐cell antigens. The atypical cells expressed EBV and HHV‐8. The patient subsequently developed a malignant pleural effusion containing the same neoplastic cell population. The findings in this case highlight the potential for unusual intravascular presentations of PEL in the skin as well as the importance of pursuing microscopic diagnosis of skin lesions in immunosuppressed patients.     

Cutaneous granulocytic sarcoma in myelodysplastic syndrome

Granulocytic sarcoma is an extramedullary tumor of immature cells of granulocytic series, generally associated to acute myelogenous leukemia. The skin is one of the most commonly affected sites. Granulocytic sarcoma can complicate myelodysplastic syndromes and is considered a sign of poor prognosis. They are often misdiagnosed with non-Hodgkin lymphoma of the lymphoblastic type, Burkitt lymphoma and large cell lymphoma. In children, the differential diagnoses also include small, round cell tumors. It is important to diagnose these lesions early because they can precede peripheral blood and bone marrow transformation to acute myelogenous leukemia. We report a case of an elderly patient with myelodysplastic syndrome who developed multiple cutaneous granulocytic sarcoma lesions and discuss prognostic and treatment implications.     

Squamous cell carcinoma in a renal transplant recipient with linear porokeratosis.

A 40-year-old man developed squamous cell carcinoma on a perianal lesion of linear porokeratosis after renal transplantation. The tumor metastasized to the left inguinal lymph node 25 months after the primary tumor was excised. p53 overexpression was observed in the tumor cells, but not in the porokeratotic lesion. Interestingly, continuous subcutaneous infusion of peplomycin for the lymph node metastasis significantly improved the warty lesions of porokeratosis. In this patient, immunosuppressive agents might have accelerated the development of carcinoma on a skin area with malignant potential.     

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.     

间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤泛发性皮肤侵犯一例

患者男,37岁,入院前7个月无明显诱因右大腿出现一鹅蛋大小肿物,无明显不适,肿物逐渐增大,右大腿、臀部出现弥漫性、非凹陷性肿胀,入院前2个月全身皮肤出现暗红色丘疹、结节、斑块,部分斑块渐出现大小不一的糜烂、溃疡。实验室检查：白蛋白降低,乳酸脱氢酶显著升高。B超示浅表淋巴结肿大、融合,彩色多普勒示淋巴结内部较丰富的树枝样血流信号。CT显示右大腿及会阴部广泛淋巴结肿大伴软组织水肿,上腹部广泛淋巴结肿大,纵膈内淋巴结肿大。皮损组织病理：真皮全层致密分布单一核细胞,部分有异形性及不典型核分裂;免疫组化：CD3、CD8、CD30（阳性细胞占80%）、CD4、CD45RＯ、粒酶B 阳性,CD56、间变性淋巴瘤激酶（ＡＬＫ）、T细胞胞质内抗原1阴性。淋巴结病理：淋巴结结构完全破坏,肿瘤弥漫成片生长,肿瘤细胞比一般的大细胞淋巴瘤瘤细胞大,胞质丰富,嗜碱性或嗜双色性,细胞核偏位,呈马蹄形、肾形或分叶状,核染色质稀疏,可见单个或多个嗜碱性小核仁;免疫组化：CD2、CD4、CD3、粒酶B、上皮膜抗原（EMA）、Ki-67、CD30阳性,CD8、CD56、T细胞胞质内抗原（TIA）-1、ＡＬＫ均为阴性。诊断：间变性淋巴瘤激酶阴性的原发系统型间变性大细胞淋巴瘤泛发性皮肤侵犯。     

Cutaneous granulocytic sarcoma arising at the site of radiotherapy for breast carcinoma

Carcinogenic effects of radiotherapy in breast cancer are well-known. Long-term follow-up of these patients shows a significantly increased risk of leukemia. Cutaneous granulocytic sarcoma is an uncommon leukemia cutis that usually occurs in association with acute myelocytic leukemia or myeloproliferative disorders. We report a case of cutaneous granulocytic sarcoma in a 44-year-old woman who had been treated six months earlier for breast adenocarcinoma. The treatment had associated lumpectomy, axillary lymph node dissection and radiotherapy. Skin lesions appeared firstly and predominantly on the irradiated area. Haematological investigations were normal and the diagnosis of isolated sarcoma was made. The uncommon features of this case were the short interval between radiotherapy and the occurrence of leukemia skin lesions and the fact that, to our knowledge, this is the first report of leukemia cutis localised on the irradiated area. The responsibility of radiation in the distribution of cutaneous lesions of granulocytic sarcoma is discussed.     

Pediatric case of anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm

A 5‐year‐old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK‐positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK‐positive ALCL limited to the skin and reviews the medical published work.     

Neutrophil-rich anaplastic large cell lymphoma presenting in the skin

A neutrophil-rich anaplastic large cell lymphoma (ALCL) presented in the skin of a 47-year-old Japanese woman. The solitary cutaneous lesion was an eroded, 10-mm, dome-shaped nodule involving the skin of her left upper arm. Histologically, it showed a proliferation of pleomorphic, anaplastic, large tumor cells with nuclei of various shapes, including embryo-shaped, Reed-Sternberg cell-like binucleated, and wreath-shaped multiple nuclei, in the dermis and subcutaneous tissues. There was an admixture of neutrophils ranging from about 30% to more than 50% per field. Immunophenotypically, the neoplastic cells were positive for CD30, CD4, leukocyte common antigen, anaplastic lymphoma kinase-1, epithelial membrane antigen, and granzyme B. She had no peripheral neutrophilia. The lesson was excised, and the site on the left upper arm was irradiated. Six and a half months after diagnosis, however, swelling of a left axillary lymph node appeared; it also showed a proliferation of anaplastic large tumor cells admixed with numerous neutrophils ranging from about 25% to more than 60% per field. Southern blot analysis of T-cell receptor gene rearrangement revealed a clonal band. The patient was treated with six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy with complete remission. Seventeen cases of neutrophil-rich ALCL arising in the skin, lymph node, muscle, testis, and skull bone were reviewed. This form may possibly be induced by trauma or irritation of conventional ALCL, although the true mechanism for the infiltration of neutrophils is still unclear.     

Akute generalisierte Katzenkratzkrankheit bei myelodysplastischem Syndrom

In patients with normal immunity, cat scratch disease typically develop a papule at the portal of entry and no other cutaneous features. A 73 year old male patient with a myelodysplastic syndrome developed generalized petechial, papular and, vasculitic skin lesions in association with cat scratch disease. After the diagnosis was established by identifying the causative organism in a lymph node biopsy, the patient was treated with erythromycin for three weeks resulting in progressive clearance of the skin lesions. Apart from the soluble IL-2 receptor, no other serologic inflammatory parameters were elevated. IgG antibodies against Bartonella henselae and Bartonella quintana increased only slightly during acute exacerbation of the disease, but significantly increased some months later. The diagnosis was established by the positive staining of the lymph node biopsy using the Warthin-Starry stain.     

Epidermotropic secondary cutaneous involvement by relapsed angioimmunoblastic T‐cell lymphoma mimicking mycosis fungoides: a case report

Angioimmunoblastic T‐cell lymphoma (AITL) is frequently associated with skin lesions, but epidermotropic cutaneous involvement has never been described. A 37‐year‐old man presented with erythematous and pruriginous plaques, clinically suggestive of mycosis fungoides, distributed all over the body, 3 weeks after the last line of a polychemotherapy, given for an AITL diagnosed 1 year earlier on a lymph node biopsy. Skin biopsy showed an epidermotropic CD4⁺ T‐cell lymphoma, so that a diagnosis of mycosis fungoides was first proposed. Further investigations showed that atypical lymphocytes strongly expressed CD10 and markers of follicular helper T cells (T_FH) including PD1, BCL‐6 and CXCL13. The diagnosis of an unusual epidermotropic cutaneous localization of the AITL was finally made, supported by the presence of the same T‐cell clone in the initial lymph node biopsy and the skin. We therefore recommend performing markers of T_FH cells in patients with unusual epidermotropic cutaneous T‐cell lymphomas, particularly if they have any clinical features suggestive of AITL.