CD56: a useful marker for diagnosing Merkel cell carcinoma

BACKGROUND: Merkel cell carcinoma (MCC) of the skin is an aggressive but rare malignant neuroendocrine tumor. For its pathological diagnosis, we use a panel of immunohistochemical markers, such as cytokeratin 20 (CK 20), epithelial membrane antigen (EMA), chromogranin A, neuron specific enolase (NSE), synaptophysin, and Leu7 (CD57) to demonstrate its epithelial and neuroendocrine features. CD56, or neural cell adhesion molecule (NCAM), has been demonstrated recently as the tumor marker of the pulmonary neuroendocrine cell system. Its expression in MCC, however, has still rarely been investigated. Furthermore, in such very few previous studies on NCAM expression in MCC, all the tumor cells were not necessarily demonstrated to express NCAM. OBJECTIVES: To study the immunoreactivity of CD56 in MCC, especially using a monoclonal antibody of a clone 1B6, different from those adopted in the previous reports. METHODS: We reexamined CD56 expression immunohistochemically in five MCC cases, along with the conventional panel of markers described above, using paraffin-embedded tissue sections. RESULTS: CD56 revealed the most diffuse and intense positive staining, which was noted along the cell borders, in all specimens compared with other neuroendocrine tumor markers. CONCLUSIONS: The results of our study indicate that CD56, especially a new monoclonal antibody (clone 1B6), is a useful immunohistochemical marker for MCC.     

Elastic fiber pattern in scleroderma/morphea

Background: Scleroderma/morphea is characterized by expansion of the dermis with thickened collagen bundles and loss of CD34⁺ dermal dendrocytes. Variable elastic fiber changes have been described, but to our knowledge, no systematic study of the elastic fiber pattern correlated with CD34 expression has been reported.
Methods: To better define the typical elastic fiber morphology, we examined seven cases of normal skin and 28 cases of scleroderma/morphea ranging from inflammatory to sclerosing stages. All but four biopsies were submitted with a clinical impression of either scleroderma or morphea. CD34 immunohistochemistry was performed on 26 biopsies with available tissue.
Results: Elastic van Gieson stain showed preservation of elastic fibers in all cases. In addition, straightening with parallel orientation and compression between thickened collagen bundles was frequently present and was graded as limited in 46% and diffuse in 54% of cases. The extent of elastic fiber alteration correlated with the degree of sclerosis. A variable loss of CD34⁺ dermal dendritic cells was seen in all cases.
Conclusion: This study confirms the preservation and frequent presence of parallel, straightened and compressed elastic fibers in scleroderma/morphea and suggests that the elastic fiber pattern, in addition to CD34 immunohistochemistry, may serve as a useful diagnostic adjunct.     

CD56 staining in Merkel cell carcinoma and natural killer‐cell lymphoma: magic bullet,diagnostic pitfall,or both?

Background: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK‐cell lymphoma. Methods: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK‐cell lymphomas. Results: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK‐cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK‐cell lymphomas. Conclusions: CD56 is a sensitive marker for MCC as well as for NK‐cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis.     

Postradiation cutaneous pleomorphic rhabdomyosarcoma with extracellular collagen deposits reminiscent of so‐called amianthoid fibers

Rhabdomyosarcoma is a malignant mesenchymal neoplasm that rarely presents as primary skin tumor. So‐called amianthoid fibers are hyalinized collagen mats that have been described in myofibroblastic tumors but not in rhabdomyosarcoma. A 65‐year‐old male developed a submandibular nodule 9 years after an oral squamous cell carcinoma, which had been treated with chemotherapy and radiotherapy. Histological examination of the nodule revealed a pleomorphic rhabdomyosarcoma with extracellular collagen deposits reminiscent of so‐called amianthoid fibers. By immunohistochemistry, the tumor cells were positive for vimentin, desmin, smooth muscle actin (SMA), muscle‐specific actin (MSA), CD10, CD56, CD99, β‐catenin and D2‐40. However, only 15–20% of the tumor cells were positive for myoglobin, MyoD1 and myf‐4/myogenin. We describe first so‐called amianthoid fibers harboring blood capillaries in a rhabdomyosarcoma, suggesting that they are rigid collagen structures that lead to tumor vascularization. The low expression for myogenic regulatory proteins and strong expression for other markers may be misleading and do not contribute to the diagnosis of rhabdomyosarcoma.     

Differentiating spitzoid melanomas from Spitz nevi through CD99 expression

BACKGROUND: A true diagnostic marker differentiating Spitz nevi (SN) from spitzoid melanoma (sMM) has been elusive. CD99, a transmembrane glycoprotein, believed to play a role in many neoplastic processes, has yet to be investigated in this regard. Recently, the expression of CD99 has been shown in 60% of primary melanomas. Other studies exploring the expression of CD99 in melanocytic lesions have not been performed. Here, we evaluate the presence of CD99 in these two histologically difficult to differentiate entities. METHODS: Cases of sMM were selected based on the presence of key microscopic words: spitz, spindled and/or epitheliod. In addition, all the cases of SN over the past 7 years were retrieved. Each case was stained with anti-human CD99 and analyzed for the presence of CD99 staining. RESULTS: Fifteen of 27 cases (56%) of sMM expressed CD99 compared with only 3 of 58 cases (5%) of SN. CONCLUSIONS: This study shows 56% of sMM and only 5% of SN express CD99. Eight of the sMM showed strong diffuse staining, a pattern not seen in any of the SN. This study does not elucidate the role that CD99 plays in these melanocytic processes; however, it does show that CD99 can be a useful tool in distinguishing sMM from SN.     

Cellular neurothekeoma with neuroendocrine differentiation

We report a case of cellular neurothekeoma with unusual clinicopathological features in which neuroendocrine markers, determined by immunohistochemistry were observed. Histologically, the tumor showed a micronodular architecture with hypercellular lobules composed of slightly spindled to epithelioid cells, with nuclear atypia or pleomorphism and extension into fat, skeletal muscle. Neoplastic cells were immunoreactive for NKI/C3, CD68, CD10, and smooth-muscle actin, whereas S100 and HMB-45 staining was negative. An intriguing feature was the strong expression by tumor cells of different neuroendocrine markers. Clinical follow up showed no local recurrences after five months despite the presence of positive margins. The presence of atypical histopathological features may cause diagnostic problems with malignant mesenchymal tumors, nevo-melanocytic lesions, and fibrohistiocytic tumors. The immunohistochemical profile including the positive staining for neuroendocrine markers may suggest divergent differentiation or an origin from myofibroblast and neuroendocrine cells.     

A rare case of intravascular large T-cell lymphoma with an unusual T helper phenotype

Although most cases of intravascular large cell lymphoma exhibit a B-cell phenotype, less than 50 cases in the literature describe a T-cell or natural killer cell phenotype and, of these, the majority are CD3+, CD4-, CD5-, CD30-, CD56+, TIA-1+, and EBER+. We present a case of a rare intravascular large T-cell lymphoma in a 59-year-old man with an unusual CD3+, CD4+, CD5-, CD30+, CD56-, TIA-1-negative and EBER-negative phenotype. This T helper or CD30 phenotype is particularly uncommon. To our knowledge, it has only been described once before and never in the absence of the cytotoxic marker TIA-1. This case exemplifies the particular diagnostic challenges raised by intravascular large cell lymphomas generally and should encourage the use of endothelial immunohistochemical staining in questionable cases. While evaluating skin punch biopsies, it is critical to keep this rare entity on the differential diagnosis along with the relatively more common intravascular large B-cell lymphoma and epithelial malignancies. Additionally, our understanding of intravascular large natural killer/T-cell lymphoma as a heterogeneous phenotypic entity continues to evolve. This case demonstrates that the degree of this phenotypic heterogeneity may be even greater than previously thought.     

CD56+ lymphoma with skin involvement: clinicopathologic features and classification

BACKGROUND: Extranodal lymphomas expressing CD56 (neuronal cell adhesion molecule) are characterized by a high incidence of cutaneous involvement and a very aggressive clinical course. Knowledge about the prognosis and clinicopathologic features of CD56(+) lymphomas with skin involvement is very limited. OBJECTIVES: To determine survival and prognostic factors for extranodal CD56(+) lymphomas with skin involvement and to describe their clinicopathologic features. DESIGN: Retrospective literature survey and case studies. PATIENTS: A total of 181 patients with CD56(+) lymphoma involving the skin: 177 cases from the literature and 4 new cases. MAIN OUTCOME MEASURE: Survival and its dependence on the following putative prognostic factors: staging, histopathologic findings, lymphocyte markers, T-cell receptor gene rearrangement, Epstein-Barr virus infection, treatment modality. RESULTS: Three major subtypes of CD56(+) lymphoma in the skin were distinguished: blastic lymphoma, nasal-type natural killer-cell/T-cell lymphoma, and subcutaneous panniculitislike lymphoma. The disease disseminated readily, mainly to lymph nodes, bone marrow, the central nervous system, and the liver, but 45% of patients had a purely cutaneous disease at presentation. All subtypes had a very aggressive course with a median survival of 14 months. The main risk factors were age older than 55 years (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.8-3.2), systemic dissemination at presentation (HR, 2.0; 95% CI, 1.5-3.3), and lack of CD30 (HR, 3.8; 95% CI, 1.4-4.9) or CD4 expression (HR, 1.56; 95% CI, 1.06-2.57). The different treatment modalities did not improve survival. CONCLUSIONS: CD56(+) lymphomas involving the skin are rare and extremely aggressive regardless of their histologic presentation and the extent of skin involvement. No effective treatment is available. The risk of death is particularly increased in older patients with CD30(-)CD4(-) lymphomas.     

皮肌炎和多发性肌炎肌肉微血管病变的病理和免疫病理改变

目的 探讨皮肌炎 （dermatomyositis,DM）的肌肉病理特征、肌纤维间的微血管改变以及与多发性肌炎（polymyositis,PM）肌肉病理的差异。方法 对16例DM和5例PM患者行肌肉活检,9例健康人骨外伤患者为对照组,做常规组织病理学检测和免疫组化染色（CD34、CD61）。 结果 37.5%DM患者有束周萎缩,肌纤维间微血管周围有较明显炎症细胞浸润的为18.8%,而PM及正常组的肌肉中未见束周萎缩。DM患者肌纤维间CD34标记的微血管数明显减少,而PM正常;16例DM中5例CD61呈阳性表达（束周区）,5例为弱阳性,阳性率为62.5％;PM仅1例呈弱阳性;正常对照组为阴性。结论 肌纤维间的微血管减少和新生血管形成也是DM肌肉病变的特征之一,该特征可用于DM与PM肌肉病理的鉴别。     

Recurrent primary cutaneous mucinous carcinoma with neuroendocrine differentiation: case report and review of the literature

We report the case of a 60‐year‐old woman presenting with primary cutaneous mucinous carcinoma (PCMC) with neuroendocrine differentiation, revealed by neuroendocrine tumor lymph node metastasis 7 years before identification of the skin tumor. Only five cases of PCMC with neuroendocrine differentiation have been reported to date. The frequency of this neuroendocrine component may be underestimated, as it can require immunohistochemistry for identification, rather than being obvious on initial histopathologic examination. In the case presented here, the prominent neuroendocrine component displayed the morphological features of a well‐differentiated neuroendocrine tumor with expression of common neuroendocrine markers, strong expression of estrogen and progesterone receptors and low Ki67 proliferation index (5%). This case shows that not all primary cutaneous neuroendocrine carcinomas are Merkel cell carcinomas (MCCs). In addition to rare primary cutaneous carcinoid tumors, the diagnosis of PCMC with neuroendocrine differentiation must be considered, particularly when confronted by a mucinous tumor or lymph node metastases of neuroendocrine carcinoma of unknown origin. On the basis of this case, identification of a neuroendocrine component in a PCMC might be an adverse prognostic indicator of recurrence or of lymph node metastasis and should support wider excision margins of the tumor.     

Cutaneous natural killer/T-cell lymphoma

Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.     

An immunohistochemical analysis of radiation fibroblasts

A commonly recognized feature of chronic radiation dermatitis is the presence of mesenchymal cells with large atypical nuclei known as radiation fibroblasts. Little is known about their lineage or potential for neoplastic transformation. To investigate these properties, we examined 16 biopsy specimens in which radiation fibroblasts were present with antisera to mesenchymal determinants (FXIIIa, CD34, HHF-35), a proliferation marker (Ki-67), and a tumor-suppressor protein that is overexpressed in many cancers (p53). Radiation fibroblasts were largely negative for the markers of lineage that we employed – only 2 of 16 specimens showed strong expression of FXIIIa, with weak expression in another case. Scattered radiation fibroblasts expressed CD34 in one case. HHF-35 (muscle specific actin) stained small, dendritic cells in the superficial dermis, but not radiation fibroblasts. P53 was not detected within radiation fibroblasts in any of our cases, but was overexpressed by endothelial cells in 2 cases. Ki-67 stained rare endothelial and interstitial cells but not radiation fibroblasts. Radiation fibroblasts are immunophenotypically distinct from dermal dendrocytes and myofibroblasts. They appear to be non-cycling cells, and do not express high levels of p53 despite their marked nuclear atypia. Their phenotype argues against their possible role as progenitors of atypical fibroxanthoma (AFX) and dermatofibrosarcoama protuberans (DFSP) which are associated with ionizing radiation-induced skin damage.     

Adhesion molecules CD171 (L1CAM) and CD24 are expressed by primary neuroendocrine carcinomas of the skin (Merkel cell carcinomas)

BACKGROUND: The neuroendocrine carcinoma of the skin is a rare malignant neuroendocrine tumor, which frequently metastasizes in regional lymph nodes or visceral organs. As adhesive interactions with endothelia, leukocytes, or thrombocytes enable malignant cells to penetrate the endothelium and to circulate in blood or lymphatic vessels, we here addressed the adhesion molecules CD171 (L1CAM) and CD24, which are known to be expressed by neurons, neuroblastomas, and other malignant tumors. METHODS: Thirty-one neuroendocrine carcinomas of the skin (22 primary tumors, four recurrent tumors, and five metastases) were included in the study. Immunohistochemical staining of CD171 and CD24 was performed by the streptavidin-biotin-peroxidase-complex technique and a nickel-enhanced diaminobenzidine (DAB) reaction using the monoclonal antibodies UJ 127.11 and ML-5, respectively. RESULTS: CD171 expression was detected in most neuroendocrine carcinomas of the skin, and staining was less frequent in metastases and recurrences in comparison with primary tumors which was statistically significant. The majority of neuroendocrine carcinomas of the skin was also positive for the mucin-like adhesion protein CD24. In contrast to tumor cells, cytokeratin 20-positive Merkel cells in 12 trichoblastomas and one fibroepithelioma of Pinkus were all negative for CD171 and CD24 staining. CONCLUSIONS: Expression of CD171 and CD24 is found in most neuroendocrine carcinomas of the skin, which may be used diagnostically. Further studies will assess whether this feature may contribute to metastasis of neuroendocrine carcinomas of the skin by facilitating transendothelial migration or tumor cell dissemination as has been suggested for other malignancies.     

Specific skin manifestations in CD56 positive acute myeloid leukemia

We found 16 CD56+ cases (29.6%) among 54 acute myeloid leukemia (AML) patients; they showed significantly frequent cutaneous involvement compared to CD56- cases (43.8% vs. 15.8%, p<0.05). Four of the CD56+ AML cases with specific skin manifestations were reviewed histologically. In all cases, cutaneous leukemic cells were seen in the dermis and subcutaneous tissue with accentuation around the adnexa/nerve, but sparing the epidermis. In addition, angiocentric/ angiodestructive and prominent cohesive tumor cell growth were seen in two cases, respectively. These findings suggest that the expression of CD56 may often be associated with the cutaneous involvement in AML, and that the above histological findings should remind us of the possibility of specific skin manifestations in CD56+ AML.     

CD56+ blastic transformation of chronic myeloid leukemia involving the skin

We report on two patients with chronic myeloid leukemia (CML) who presented blastic transformation involving the skin, with leukemic infiltrates showing unusual morphologic and immunohistologic characteristics. Both patients were elderly men with a 36-month and a 40-month history of CML, respectively. They presented with disseminated, reddish to violaceous papules and plaques (case 1), and with localized reddish nodules on the left temporal area (case 2). Concurrent features of blastic transformation in the bone marrow were observed in one patient (case 1). Histopathologic examination of skin lesions revealed similar features in both cases. There was a moderate to dense dermal infiltrate composed mainly of medium-sized atypical mononuclear myeloid precursor cells with only few relatively well-differentiated cells of the granulocytic series. Histochemical staining for naphthol-ASD-chloroacetate esterase revealed strong positivity (>50% of neoplastic cells) in case 2 and only scattered positivity (< 10% of neoplastic cells) in case 1. Immunohistologic analysis performed on paraffin-embedded sections showed in both cases variable reactivity of neoplastic cells for leucocyte common antigen (CD45), lysozyme, myeloperoxidase, CD11c, CD15, CD43, CD66, CD68, HLA-DR, and the neural cell adhesion molecule (NCAM) CD56. A negative reaction was observed for CD3, CD34, and TdT. The immunohistologic findings were remarkably similar to those reported for acute myeloid leukemia (AML) with monocytic differentiation (French-American-British [FAB] classification, subtype M4). Examination of blasts from the bone marrow performed in one patient (case 1) revealed a similar phenotype also with CD56 expression. In conclusion, our observations show that specific cutaneous infiltrates in CML may show morphologic and immunohistochemical characteristics similar to those observed in AML with monocytic differentiation. Moreover, specific cutaneous manifestations of CML may express CD56.     

Procollagen 1 - a marker of fibroblastic and fibrohistiocytic skin tumors

BACKGROUND: When dealing with tumors of presumed fibroblastic or fibrohistiocytic origin, immunohistochemistry is traditionally done to exclude a tumor of non-fibroblastic or non-fibrohistiocytic nature, because a reliable marker of fibroblastic or fibrohistiocytic cell origin is still to be introduced. This study investigates whether procollagen 1 is a useful marker of skin tumors composed of cells derived from fibroblasts or fibrohistiocytes. MATERIALS AND METHODS: Twenty-nine different types of skin tumors, including tumors composed of spindle cells as well as some additional epithelial and melanocytic tumors, were stained immunohistochemically with antibodies against procollagen 1. The total number of cases tested was 154. RESULTS: Tumors composed of cells of fibroblastic or fibrohistiocytic origin in general showed a high expression of procollagen 1, whereas tumors composed of non-fibroblastic cells in general showed no expression. However, there were a few exceptions, e.g., leiomyosarcoma and desmoplastic melanoma. CONCLUSIONS: The study suggests that immunohistochemical staining for procollagen 1 is a valuable marker for skin tumors composed of spindle cells derived from fibroblasts or fibrohistiocytes. However, in cases of spindle cell tumors with a morphology suggesting malignancy, it is recommended to use a panel of antibodies, which besides procollagen 1 includes markers such as S100, CD68, CD34, h-caldesmon, and pancytokeratin.     

Myofibroblastic differentiation in atypical fibroxanthomas occurring on sun-exposed skin and in a burn scar: an ultrastructural and immunohistochemical study

Herein, we report the investigation of two cases of atypical fibroxanthoma (AFX). One AFX developed within actinically damaged skin, as is typical, while the other developed within a burn scar within non-sun-exposed skin. The two tumors showed almost identical histopathological, immunohistochemical and ultrastructural features. The tumors were composed of pleomorphic spindled, epithelioid, multinucleated and bizarre cells with enlarged atypical nuclei. Most tumor cells expressed vimentin and about 50% expressed CD10. Some tumor cells also expressed α-smooth muscle actin and CD68. However, there was no expression of cytokeratins, p63, S-100 protein, melan-A, HMB 45, desmin, epithelial membrane antigen or CD34. Ultrastructurally, the tumor cells contained myofilaments with dense patches but lacked plasmalemmal caveolae and basal lamina. The most prominent finding was the identification of fibronexus junctions. In addition, there were tumor cells containing numerous lysosomal granules. In conclusion, we clearly showed myofibroblastic differentiation in AFX by electron microscopy. We report also a case of AFX directly developing within a burn scar in the absence of actinic damage.     

CD4+/CD56+ hematodermic neoplasm: report of a rare variant with a T-cell receptor gene rearrangement

CD4+/CD56+ hematodermic neoplasm (HN), formerly known as a blastic natural killer (NK) cell lymphoma, is a rare subtype of a cutaneous dendritic cell neoplasm notable for highly aggressive behavior. The characteristic features are: expression of the T-helper/inducer cell marker CD4 and the NK-cell marker CD56 in the absence of other T cell or NK-cell specific markers. In particular, CD3 (surface or cytoplasmic) and CD2 are not expressed. Although T-cell receptor (TCR) genes are generally reported to be in a germline configuration, we present an unusual variant of a CD4+/CD56+ HN with a clonal rearrangement of TCR genes. This feature of a CD4+/CD56+ HN has been only rarely reported. Recognition of the presence of clonal TCR gene rearrangements in a small subset of CD4+/CD56+ HN is important to avoid misdiagnosis of this entity as an unusual variant of a cutaneous T-cell lymphoma.     

Expression of α subunit of guanine nucleotide-binding protein Go in Merkel cell carcinoma

The α subunit of guanine nucleotide-binding protein G_o(G_oα), which was initially isolated from bovine brain, interacts with muscarinic cholinergic receptors and regulates neuronal calcium channels. G_oα is known to be localized in neural tissues, some endocrine cells, and neuroendocrine tumors. We have immunohistochemically investigated the expression of G_oα in 4 cases of Merkel cell carcinoma using the method of microwave treatment. In all cases of Merkel cell carcinoma, G_oα was consistently detected on the plasma membrane and cytoplasm of the tumor cells. Nerve fibers in the skin were also positive for G_oα, but other epidermal or dermal components such as keratinocytes, melanocytes, fibroblasts, or lymphoid cells were negative. Tumor cells of squamous cell carcinoma, cutaneous lymphoma, sweat gland carcinoma, and malignant melanoma were negative for G_o4aL. The present study indicates that G_oα may be a useful immunohistochemical marker of Merkel cell carcinoma.     

CD56-positive (nasal-type T/NK cell) lymphoma arising on the skin

Several authors have reported cases of patients with malignant lymphoma with unique characteristics, designated nasal-type T/NK cell lymphoma, which expresses the natural killer (NK) cell marker and shows frequent extra-nodal involvement and poor prognosis. We report 2 cases of this type of lymphoma which were CD56-positive and showed a histopathologically angiocentric pattern with cutaneous and subcutaneous tumorous lesions. Patient 1 had extensive invasion of skin, underlying skeletal muscle, spleen and bone marrow, and died of sepsis 34 months after onset. Patient 2 had multiple subcutaneous nodules and invasion to mammary gland, lung, lymph node and spleen at the time of her first visit. She died of a rapid invasion of lymphoma cells to the liver 5 months after onset. Both patients showed similar immunophenotypes of tumor cells (CD2+, CD3−, CD4−, CD8−, CD20−, CD56+) and germ line configuration of the heavy chain of immunoglobulin (JH), T-cell receptor C beta-1 subunit DNA and T-cell receptor J gamma subunit DNA. Epstein-Barr virus early regions RNA was demonstrated in the nuclei of tumor cells of both patients with in situ hybridization. The histopathological examination of the skin lesions of both patients revealed the features of angiocentric lymphoma. The detection of CD56 in the tumor cells of cutaneous lymphomas should be routinely performed for the early diagnosis of this type of lymphoma with extremely poor prognosis.