Incidental chronic lymphocytic leukaemia in a biopsy of Merkel cell carcinoma

Chronic lymphocytic leukaemia (CLL) shows cutaneous involvement in 2% of cases. Merkel cell carcinoma (MCC) is a rare primary cutaneous epithelial neoplasm most commonly found in sun-exposed sites in elderly male Caucasians. A 66-year-old man presented with a 2-month history of a purple painless 2 cm tumor on the scalp. Excision biopsy revealed an incompletely excised MCC, and at the periphery of the MCC, a lymphocytic infiltrate interpreted as reactive. A re-excision biopsy showed residual MCC as well as dense aggregates of small lymphocytes within and surrounding the MCC. Immunohistochemistry showed characteristic dot-like cytoplasmic positivity for cytokeratin 20 in the MCC; the lymphocytic infiltrate was positive for CD5, CD20 and CD23, diagnostic of CLL. Subsequent staging revealed widespread lymphadenopathy, and lymph node biopsy showed CLL. Histologically, CLL and MCC are 'round blue cell tumors' and are therefore in the differential diagnoses of each other. Whenever there is a more prominent than expected infiltrate of small lymphocytes surrounding a skin lesion in an elderly patient, immunohistochemistry to rule out CLL is advised. This case adds to the literature suggesting an increased incidence of CLL and other neoplasms in patients with MCC and vice versa.     

Subclinical chronic lymphocytic leukemia with atypical cutaneous presentation

Chronic lymphocytic leukemia (CLL) involving skin is a rare but well‐documented occurrence, mainly reported in advanced disease. In contrast, CLL presenting with skin lesions is exceedingly rare, only few reports existing to date. We report a 70‐year‐old man who presented with two non‐pruritic, papular lesions on the lower abdomen and proximal thigh. Biopsies showed dense lymphohistiocytic infiltrates involving the reticular dermis and subcutis without epidermotropism consisting mostly of small, CD20 and PAX‐5‐positive B‐cells expressing CD5, CD23, CD43 and BCL2. Numerous large B‐cells were present in a T‐cell, histiocyte‐rich background. A staging bone marrow biopsy showed a clonal B‐cell proliferation with typical CLL flow cytometry immunophenotyping but neither lymphadenopathy nor absolute lymphocytosis was present. Numerous B and T‐cell cutaneous lymphoproliferative disorders can be associated with increased numbers of histiocytes occasionally masquerading as benign disorders. This was the case with our patient's lesions, originally interpreted as cutaneous Rosai–Dorfman disease. A high index of suspicion from both the pathologist and the dermatologist is essential in identifying these rare but probably underrecognized occurrences of early systemic lymphoproliferative disorders presenting as cutaneous lesions with an unexpected cellular composition. Ali L, Cheney R, Merzianu M. Subclinical chronic lymphocytic leukemia with atypical cutaneous presentation.     

Chronic lymphocytic leukaemia skin infiltrates affecting prominent parts of the face and the scalp

Chronic lymphocytic leukaemia (CLL) infiltrating the skin is uncommon and can present in different forms. We report a case of CLL infiltrating the prominent parts of the face and the scalp. A 63-year-old male with a 10-year history of CLL presented with plum-coloured swelling of the skin of the ears, eyebrows, tip of the nose and the scalp. Histopathology showed dense sheets of lymphoid infiltrate of the dermis which stained positive with B-cell markers CD20 and CD5 in keeping with the infiltrate of CLL.     

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.     

A unique case of concurrent chronic lymphocytic leukemia/small lymphocytic lymphoma and lymphomatoid papulosis in the same biopsy

Chronic lymphocytic leukemia (CLL/SLL) is the most common leukemia in the western world and its cutaneous dissemination a very uncommon phenomenon. Lymphomatoid papulosis (LyP) is a CD30+ lymphoproliferative disorder characterized by chronic, recurrent and self healing skin lesions. Up to 20% of patients with LyP have a coexistent lymphoma. While the association between the two entities has been reported, their coexistence has never been documented. We describe a 74‐year‐old man with known CLL and thrombocytopenia who presented with a 2 year history of recurrent nodules and plaques to both arms and legs that resolved within 4–6 weeks after administration of rituximab and bendamustin for his CLL treatment. His biopsies showed an atypical lymphoid infiltrate, composed of large and pleomorphic cells with a nodular and interstitial pattern in a background of eosinophils. Immunohistochemical staining revealed a pattern of two separate yet coexisting neoplastic processes; a large CD30 positive T‐cell lymphoproliferative disorder, while the other one was diagnostic of a neoplastic B‐cell process (leukemia cutis). A diagnosis of coexistent LyP and cutaneous involvement by CLL/SLL was rendered. The simultaneous presence of both disorders can be a pitfall in the differential diagnosis of large cell lymphomas, such as Richter's transformation of CLL/SLL.     

CD10, p63 and CD99 expression in the differential diagnosis of atypical fibroxanthoma,spindle cell squamous cell carcinoma and desmoplastic melanoma

Background: Atypical fibroxanthoma (AFX) is a pleomorphic spindle cell lesion of the skin; it is considered in the differential diagnosis with spindle cell malignant melanoma (MM) and sarcomatoid carcinoma/spindle cell squamous cell carcinoma (SCC). An optimum approach has yet to fully emerge with respect to the immunohistochemical discrimination of these lesions. Methods: Departmental archives from 1978 onwards were searched for clinicopathologically confirmed cases of AFX, MM and SCC. Immunostains for CD10, CD99 and p63 were performed in each case. Scored staining results were analyzed using Fisher's Exact Test. Results: Twenty‐seven of 31 cases of AFX were positive for CD10, as compared with 3 of 22 SCCs and 0 of 20 MMs. CD10 positivity was preferentially associated with the diagnosis of AFX (p < 0.001). p63 reactivity was observed in 15/22 cases of SCCs, 5/31 AFXs and 1/20 MMs. CD99 reactivity was observed in 3/31 cases of AFX, 2/22 SCCs and 3/20 MMs. Conclusion: CD10 positivity is relatively specific in this context for the diagnosis of AFX. Its utility is enhanced when only strong, diffuse membranocytoplasmic staining is considered as a positive result. In contrast to prior reports, p63 was not found to be highly sensitive for SCC. Similarly, CD99 showed no preferential staining of any single diagnostic group of lesions. Kanner WA, Brill LB, Patterson JW, Wick MR. CD10, p63 and CD99 expression in the differential diagnosis of atypical fibroxanthoma, spindle cell squamous cell carcinoma and desmoplastic melanoma.     

Primary cutaneous follicle center lymphoma in the setting of chronic lymphocytic leukemia

Primary cutaneous malignancies arising in association with chronic lymphocytic leukemia (CLL) are notable for their atypical clinical and histological presentation. We report a 69-year-old man with a 17-year history of CLL who presented for evaluation of a well-defined red to violaceous nodule with a central depressed scar on the left lower extremity. Microscopic examination of a punch biopsy revealed an infiltrate of predominantly small lymphocytes with scattered large, atypical epithelioid cells. Immunohistochemical stains revealed diffuse positive staining of the lesional cells with CD20+ and bcl-6+ and focal positive staining with bcl-2+ (negative CD10 and CD23), findings which, in conjunction with the histology, were most compatible with a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). A review of the clinical charts revealed several prior biopsies with varied diagnoses. In light of the most recent biopsy findings, all previous biopsies were re-reviewed and interpreted as PCFCL arising in the setting of CLL. Features contributing to the diagnostic conundrum in this case included an atypical clinical and histological presentation, lack of pertinent clinical history and multiple presentations at different institutions.     

Concurrent chronic lymphocytic leukemia cutis and acute myelogenous leukemia cutis in a patient with untreated CLL

Patients who have chronic lymphocytic leukemia (CLL) are known to have a high frequency of second malignant neoplasms. However, acute myelogenous leukemia (AML) occurring concurrent with or after a diagnosis of CLL is extremely rare. In this article we report a case of AML developing in a 55-year-old male with a 6-year history of untreated CLL. The diagnosis was facilitated by touch preparation of a skin punch biopsy specimen. The patient presented with a two-week history of fever, weakness, anasarca, and a skin rash. Physical examination revealed pink to skin-colored firm papules, which coalesced into indurated plaques on his trunk, upper extremities, and face. The lesions, in combination with generalized edema, produced a leonine facies. Touch prep of the biopsy showed medium to large blasts, large monocytoid cells, and numerous small mature lymphocytes, providing the preliminary diagnosis of a second, previously undiagnosed myelomonocytic malignancy in this patient. The initial diagnosis was subsequently confirmed by histologic, cytochemical, immunohistochemical and flow cytometry studies. This is the first reported case of CLL with concurrent AML in which rapid touch prep of a skin punch biopsy facilitated diagnosis.     

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.     

硬皮病样皮肤转移性恶性纤维组织细胞瘤1例

报告1例硬皮病样皮肤转移性恶性纤维组织细胞瘤。患者男,60岁。面颊及颈部皮肤硬韧1个半月。病理检查示:真皮浅中层胶原纤维间见散在或密集的类似成纤维细胞样细胞、组织细胞样细胞浸润,细胞核大而深染,呈长梭形及圆形,小血管腔内也见核大深染的细胞及多核巨细胞。免疫组化示:CD68(+),CD34,CK,SMA均阴性。诊断:皮肤转移性恶性纤维组织细胞瘤。     

套细胞淋巴瘤伴皮肤虫咬样反应一例

【摘要】 患者男,74岁,确诊套细胞淋巴瘤5年,躯干、四肢丘疱疹伴瘙痒10个月就诊。皮疹瘙痒剧烈,给予抗组胺药物对症治疗不能缓解。体检：躯干、四肢皮肤见散在绿豆至黄豆大小红色丘疹及丘疱疹,部分表面见浅表结痂,以双上肢皮损为主,颈部、双侧腹股沟可触及肿大淋巴结,约2 cm × 1 cm。颈部淋巴结病理示,正常淋巴结结构完全破坏,中等大淋巴样细胞呈结节状或弥漫增生浸润,免疫组化示CD20（+++）,CD79α（+++）, Bcl-2（++）,细胞周期蛋白D1（+++）,CD5（++弱）,CD43（++）,Bcl-6（++）, PAX-5（+++）,κ（+++）,λ（±） ,Ki-67（10% ~ 30%+不均）。皮损组织病理及免疫组化：表皮大致正常,真皮浅中层血管、附属器周围见以中等大小淋巴样细胞为主的团灶状浸润,其间散在嗜酸性粒细胞;免疫组化：CD3（部分+）,CD5（弥漫性+）,CD20（部分+）,细胞周期蛋白D1（部分+）,Ki-67（10% +）。根据临床资料、淋巴结及皮损组织病理及免疫组化,诊断为套细胞淋巴瘤伴皮肤虫咬样反应。     

Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathologic overlap with primary cutaneous B‐cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61‐year‐old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B‐cells colonizing germinal center follicles; however, faint CD5 and CD23 co‐expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count of CLL‐type monoclonal B lymphocytosis. Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B‐cell lymphomas presenting in the skin.     

Nonclonal lymphocytic proliferation in cutaneous lymphoid hyperplasia: a flow-cytometric and morphological analysis.

Cutaneous lymphoid hyperplasia, follicular B cell pseudolymphoma or lymphadenosis benigna cutis and lymphocytic infiltration of Jessner-Kanof are a group of benign lymphoid hyperplastic disorders which usually involve the skin of the face or head and neck. These lesions may be difficult to differentiate from malignant lymphocytic lymphomas both morphologically and clinically. To evaluate whether quantitative flow-cytometric analysis and DNA ploidy determination of the lymphoid cells in the lesions would provide additional and more precise diagnostic parameters, we have correlatively analyzed a case by morphological, flow-cytometric and immunohistochemical methods. The two latter methods both revealed that the lesions harbored nonclonal heterogeneous subpopulations of lymphoid cells, but 62% of the cells analyzed were of B cell lineage progenies. No pre-B cells, immature B or T determinants were detected. Ploidy analysis of the isolated lymphocytes disclosed predominantly diploid (2 N) cells with about 1% 4 N and a few (less than 5%) hyperdiploid (2.2 N) cells. Cell cycle analysis showed that 97.2% of the cells were in G0-G1 phase. Phenotyping and DNA ploidy study of the lymphocytes of the lesion may provide quantitative diagnostic parameters to distinguish this benign lesion from true lymphocytic lymphoma involvement of skin. The eventual biological behavior of the minor hyperdiploid subpopulation of lymphoid cells found in this lesion is currently uncertain, however.     

Immunoreactivity of CD99 in invasive malignant melanoma

BACKGROUND: CD99, also known as p30/32, is a glycoprotein product of the MIC2 gene. It was originally utilized in immunohistochemistry as a unique marker for Ewing sarcoma, other primitive neuroectodermal tumors, and subsequently in other tumors. Its expression in malignant melanoma (MM) has not been well documented, with just two isolated cases of MM recently reported. Recent studies have documented CD99 expression in a significant percentage of atypical fibroxanthomas (AFX), posing potential diagnostic problems in differentiating these two entities. As mistaking MM for AFX based on immunohistochemical staining pattern has significant consequences, we sought to determine the percentage of invasive MM in our archives that have this staining pattern. METHODS: Seventy-eight cases of invasive melanoma were retrieved from our files. Each case was stained with mouse anti-human CD99 and evaluated for membranous expression. RESULTS: Our evaluation revealed that 47 of 78 MM cases (60%) stain positive for CD99. CONCLUSION: This study is the first to demonstrate, in a large series, the prevalence of CD99 expression in primary cutaneous melanoma. Additionally, this introduces in the histologic differential diagnosis of CD99 expressing dermal spindle cell lesions.     

播散性带状疱疹后肉芽肿性炎型Wolf同位反应一例

【摘要】 患者男,65岁,因右面部红肿20 d,背部、双上肢散在丘疹10 d入院。发病前20 d曾因播散性带状疱疹住院治疗。确诊慢性淋巴细胞白血病3年。皮肤科检查：右面部眼睑以下区域、耳廓及外耳道弥漫性暗红色肿胀性斑块,触之有浸润感,原带状疱疹愈合后遗留散在褐色结痂,其间可见散在凹陷性瘢痕;颈后、背部及双上肢可见散在浸润性淡红色丘疹,绿豆至黄豆大小,表面较光滑。面部皮损组织病理检查：真皮全层及皮下脂肪层可见上皮样细胞和淋巴细胞呈结节状浸润,并含较多多核巨细胞;免疫组化：CD68、CD20、CD79a、CD3、CD2、CD10、CD5、Bcl-2阳性、Ki-67散在阳性,CD23、细胞周期蛋白D1、Bcl-6、多发性骨髓瘤癌基因1、CD21、CD35、髓过氧化物酶均阴性。诊断：播散性带状疱疹后肉芽肿性炎型Wolf同位反应。治疗：静脉滴注甲泼尼龙40 mg/d,皮损逐渐好转消退,随访4年未复发。     

CD34 expression in desmoplastic melanoma

BACKGROUND: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma. METHODS: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression. RESULTS: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy. CONCLUSION: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.     

CD44V6在表皮肿瘤及恶性黑素瘤的表达

目的　研究CD44V6在鳞状细胞癌、基底细胞癌和恶性黑素瘤的表达。方法　免疫组织化学对石蜡包埋组织标本进行检测。结果　 1 0例鳞状细胞癌CD44V6膜表达阳性 ,且随癌细胞分化程度降低CD44V6表达下调。 1 0例基底细胞癌和 8例恶性黑素瘤不表达CD44V6。结论　CD44V6的表达与皮肤肿瘤的类型有关     

A case of malignant lymphoma of the nodular, poorly differentiated lymphocytic type.

A case of malignant lymphoma of the nodular, poorly differentiated lymphocytic type was presented. The patient, a 72-year-old woman, exhibited cutaneous nodules, generalized lymphadenopathy and splenomegaly. Treatment with two courses of steroid therapy and radiotherapy was carried out. After this therapy, skin tumors responded excellently. Histopathological findings of lymph nodes included proliferating forms of lymphoid tumor cells consisting of nodular and diffuse patterns. Peripheral lymphoid tumor cells, which had cleaved nuclei, clear nucleoli and mitoses were 30% increased in peripheral lymphocytes. Furthermore, the percentage of B cells in the subpopulation of peripheral lymphocytes was high, and that of T cells was low. In the present report, the histopathological and autopsy findings were studied, and some aspects of the classification of malignant lymphoma were discussed.     

Leukemia cutis in B-cell chronic lymphocytic leukemia presenting as an episodic papulovesicular eruption

A 53-year-old man presented with a recurrent pruritic eruption accompanied by oral sores. His past medical history was significant for subclinical B-cell chronic lymphocytic leukemia (CLL), which had never been treated. On exam, there were erythematous papules and plaques studded with vesicles on the neck, trunk, and upper extremities. Two skin biopsies showed common features of a perivascular and periadnexal lymphocytic infiltrate in the superficial to mid-dermis. Immunohistochemical staining of the lymphocytes showed co-expression of CD20, CD23, CD5, and CD43, consistent with a diagnosis of cutaneous involvement by the patient's CLL. This case highlights the importance of considering leukemia cutis in patients with underlying CLL presenting with unusual clinical features.     

Atypical fibroxanthoma with lymphomatoid reaction

Background: Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun‐damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30‐positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. Methods: The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T‐cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Results: Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S‐100, cytokeratins and muscle markers, thereby confirming the diagnosis of AFX. CD30 highlighted a significant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. Conclusion: An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma. Zheng R, Ma L, Bichakjian CK, Lowe L, Fullen DR. Atypical fibroxanthoma with lymphomatoid reaction.