A case of blastic plasmacytoid dendritic cell neoplasm with ecchymotic lesions on the whole body

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as “eczema”. The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months.     

Sustained complete remission of a limited-stage blastic plasmacytoid dendritic cell neoplasm followed by a simultaneous combination of low-dose DeVIC therapy and radiation therapy: a case report and review of the literature

The patient was a 74-year-old man who was found to have a cutaneous mass on his left shoulder in February 2012. Because the mass bled easily and was tending to grow, total resection of the cutaneous tumor, which measured approximately 5 cm x 3 cm, was performed in July. Histopathological examination revealed a tumor that extended from the dermis to the cutaneous adipose tissue, but no invasion of the epidermis was seen. The tumor cells were plasmacytoid cells ranging in size from small to intermediate, and there was no nuclear irregularity. They had a high nuclear-cytoplasmic ratio, and nucleoli were observed. The tumor cells were CD4-positive, CD56-positive, and CD123-positive, and they were AE1/AE3-negative, CD3-negative, CD20-negative, and myeloperoxidase-negative. ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT), a bone marrow examination, etc., were performed, but no lesions were detected at other sites. Based on the above findings a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN), Stage IEA, was made. Because the patient had limited-stage BPDCN and was elderly, we treated him with a simultaneous combination of low-dose DeVIC (dexamethasone, VP16, ifosfamide, and carboplatin) therapy and local radiation therapy (LRT) and sustained a complete remission for approximately 1 year. Simultaneous combination of non-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and LRT appeared to be useful in the treatment of limited-stage BPDCN even in the elderly.     

Pleomorphic rhabdomyosarcoma arising in the anterior mediastinum: A case report with cytological features of imprint and liquid‐based cytology specimens

We herein report the cytological features of a very rare case of pleomorphic rhabdomyosarcoma arising in the anterior mediastinum on imprint and liquid‐based cytology (LBC) specimens. A 58‐year‐old man had an approximately 10‐cm tumor in the anterior mediastinum as shown on computed tomography. Thymectomy with complete resection of the left lung was performed. The fresh cut surface of the tumor was used to prepare imprint and LBC specimens. The imprint specimens showed four types of tumor cells dispersed on a background of hemorrhage, necrosis, and mucus. On the other hand, only two types of tumor cells (spindle‐shaped and spiderweb cells) were scattered or present in clusters in the LBC specimens. Immunocytologically, both of these cell types were positive for desmin and myoglobin, negative for pan‐keratin and epithelial membrane antigen. Cytological and immunocytological features are useful for the correct diagnosis of pleomorphic rhabdomyosarcoma, and LBC specimens show clearer results than do imprint specimens. Diagn. Cytopathol. 2017;45:333–338. © 2016 Wiley Periodicals, Inc.     

The diagnostic utility of Merkel cell polyomavirus immunohistochemistry in a fine needle aspirate of metastatic Merkel cell carcinoma of unknown primary to the pancreas

Merkel cell carcinoma (MCC) is an aggressive skin tumor with a high tendency for metastases. We report a case of MCC initially presenting as axillary and pancreatic metastases. A 33‐year‐old HIV‐positive Hispanic male presented with a history of a rapidly growing axillary mass. A needle core biopsy demonstrated an epithelioid neoplasm composed of small to medium‐sized cells with high nuclear‐cytoplasmic ratio, nuclear molding, and frequent mitotic figures. A subsequent PET scan revealed a 1.5 cm FDG avid mass in the pancreas. Endoscopic ultrasound‐guided FNA of the pancreatic mass showed neoplastic cells with similar morphology to those of the axillary mass. The tumor cells were positive with pancytokeratin AE1/AE3, CK20, CD56, synatophysin, chromogranin, and Merkel cell polyomavirus (MCPyV). This case of MCC most likely originated from a resolved primary skin lesion drained by the involved axillary lymph node with subsequent metastases to the pancreas and distant lymph nodes.     

Collision tumor of primary merkel cell carcinoma and chronic lymphocytic leukemia/small lymphocytic lymphoma,diagnosed on ultrasound‐guided fine‐needle aspiration biopsy: A unique case report and review of literature

We report an extremely rare case of skin collision tumor between primary Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) first diagnosed on ultrasound‐guided fine‐needle aspiration biopsy (US‐FNA). A 95‐year‐old female with a history of CLL presented with a slow growing left malar mass was referred to our clinic for US‐FNA. US scan showed a well‐defined subcutaneous mass (2.78 cm) with complex echogenicity. On‐site assessment showed a cellular aspiration which was interpreted as small blue round cell tumor. On further examination, smears and cell block showed dimorphic populations of relatively larger cells with neuroendocrine features and smaller lymphoid cells. Immunocytochemical studies of cell block sections revealed that the larger cells were positive for CD56, Chromogranin, Synaptophysin, CK8/18, CK20 (dot‐like pattern); and the smaller cells were positive for CD45. Flow cytometric analysis showed a majority of CD16/CD56 positive cells, 17% of monoclonal B‐cells, and 14% of reactive T cells. The immunophenotype of the monoclonal B cells were of CLL/SLL. The diagnosis of a collision tumor composed of primary MCC and CLL/SLL was confirmed. Surgical resection of the mass one month later concurred with the FNA cytological diagnosis. The fact that surgical specimen displayed a solid tumor with both CLL/SLL and MCC components ruled out the possibility that the FNA merely had MCC with peripheral leukemic blood contaminant. No additional MCC lesion was found in the patient, which ruled out the possibility of metastatic MCC to a lymphomatous lymph node. Diagn. Cytopathol. 2015;43:66–71. © 2014 Wiley Periodicals, Inc.     

CLTC‐ALK fusion as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a subtype of acute myeloid leukemia, affecting mainly the elderly. It is thought to be derived from plasmacytoid dendritic cell precursors, which frequently present as cutaneous lesions. We have made a detailed analysis of an infant with BPDCN, who manifested with hemophagocytic lymphohistiocytosis. The peripheral blood leukocytes revealed the t(2;17;8)(p23;q23;p23) translocation and a CLTC‐ALK fusion gene, which have never been reported in BPDCN or in any myeloid malignancies thus far. Neonatal blood spots on the patient's Guthrie card were analyzed for the presence of the CLTC‐ALK fusion gene, identifying the in utero origin of the leukemic cell. Although the leukemic cells were positive for CD4, CD56, CD123, and CD303, indicating a plasmacytoid dendritic cell phenotype, detailed analysis of the lineage distribution of CLTC‐ALK revealed that part of monocytes, neutrophils, and T cells possessed the fusion gene and were involved in the leukemic clone. These results indicated that leukemic cells with CLTC‐ALK originated in a multipotent hematopoietic progenitor in utero. This is the first report of the CLTC‐ALK fusion gene being associated with a myeloid malignancy, which may give us an important clue to the origin of this rare neoplasm. © 2013 Wiley Periodicals, Inc.     

Tumor imprint cytology of sclerosing stromal tumor of the ovary

Over 90 cases of sclerosing stromal tumor of the ovary (SST) have been reported in the English-language literature, but these authors did not mention the cytologic examination of SST. In 2 patients with SST, we were able to collect specimens for tumor imprint cytology. The number of cells in the specimens was extremely small. Two types of benign cells were observed against a clean background, comprising cells with round nuclei surrounded by abundant cytoplasm and cells with spindle-shaped or oval nuclei that had scanty cytoplasm. Our present findings suggest that intraoperative imprint cytology was able to rule out cancer. Considering that SST most commonly occurs in young women requiring conservative treatment, imprint cytology seems to have a potential diagnostic significance.     

Superficial CD34‐positive fibroblastic tumor: Cytologic features,tissue correlation,ancillary studies,and differential diagnosis of a recently described soft tissue neoplasm

Superficial CD34‐positive fibroblastic tumor is a low‐grade mesenchymal neoplasm of superficial soft tissues characterized by fascicles of spindle to epithelioid cells displaying nuclear pleomorphism and strong diffuse CD34 immunoreactivity. The intraoperative imprint cytology preparations (ICP) of a superficial CD34‐positive fibroblastic tumor from a 50‐year‐old female are described. To the best of our knowledge, there is no report of the cytologic findings of superficial CD34‐positive fibroblastic tumor in the English medical literature. The ICP, differential diagnosis, tissue correlation, and ancillary studies of this fascinating entity are discussed. Diagn. Cytopathol. 2016;44:926–930. © 2016 Wiley Periodicals, Inc.     

TDT (-), KIT (+), CD34 (+), CD99 (+) precursor T lymphoblastic leukemia/lymphoma

Although the definition of precursor T lymphoblastic lymphoma (T-LBL) is based only on histopathology, most cases cannot be diagnosed only by HE sections. Since 95% of T-LBL expresses TdT and TdT is expressed only in lymphoblasts, immunohistochemical demonstration of TdT is mandatory for the diagnosis of TLBL. However, little is known about the expression of other precursor cell molecules. A 58-year-old woman with myelodysplastic syndrome (RAEB) became overt acute myelogenous leukemia (AML). She was treated twice with allogeneic peripheral blood stem cell transplantation from her son. Nine months later, imaging modalities detected a soft tissue tumor around the left ileal bone. A biopsy was performed. Histologically, the tumor cells were malignant polymorphic lymphoid cells with hyperchromatic nuclei and inconspicuous nucleoli. Immunohistochemically, the tumor cells are positive for CD45, CD45RO, CD34, KIT (CD117), CD99 (MIC-2), p53, CD10, PDGFRA, and Ki67 (labeling=60%). They were negative for pancytokeratin AE1/3, pancytokeratin CAM5.2, TdT, CD3, CD20, CD79α, CD43, CD56, CD57, CD30, bcl-2, κ-chain, λ-chain, cytokeratin (CK) 7, CK20, synaptophysin, chromogranin, smooth muscle actin, p63, MPO, CD68, lysozyme, and ASD esterase. Although TdT was negative, other precursor cell markers (KIT, CD34, and CD99) were positive and the lymphoid cells showed T-cell lineage, the diagnosis was T-LBL. The patient died of lymphoma/ leukemia 11 months after the diagnosis. The author stress that TdT, KIT, CD34 and CD99 should be included in panels of precursor T-cell neoplasms. In addition, the author think that KIT, CD34 and CD99 are helpful for the diagnosis of T-LBL in cases negative for TdT. Further, it is unique that this case was not myeloid sarcoma but precursor T-cell neoplasm, and that T-LBL develops during AML.     

CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance.

AIMS--To determine whether a particular phenotype or antigen is preferentially related to monoclonal gammopathies of undetermined significance (MGUS). METHODS--Bone marrow specimens from 56 patients with MGUS were stained immunocytochemically (ABC peroxidase) for CD38, CD56, CD9, CD10, CD19, CD20, CD22, and MB2. Specimens from patients recently diagnosed with multiple myeloma and reactive bone marrow samples were studied in parallel. RESULTS--CD38 was expressed on all plasma cells from all MGUS samples tested, while 36% were positive for CD56, CD9 and MB2 were both expressed strongly; CD20 was moderately expressed, and staining for CD10 and CD22 was uncommon. For these five B cell antigens there was no clear difference between their expression in MGUS and in multiple myeloma. A great difference was found for CD19: in MGUS this antigen was expressed on 2-91% of plasma cells (mean 35%) and 77% patients had > 10% positive plasma cells; in multiple myeloma its expression was low and only 12% patients had > 10% positive plasma cells. When these results were converted to numbers of CD19 positive plasma cells per 100 nucleated bone marrow cells, reactive bone marrow and MGUS specimens had a similar number of positive plasma cells. There was no correlation between expression of any of the antigens tested. CONCLUSIONS--Many of the so-called pre-B, B or activation antigens are present on plasma cells from MGUS specimens, and expression of CD9, CD10, CD20, CD22, MB2, and CD38 in MGUS was very similar to that in multiple myeloma. CD56 was frequently expressed in MGUS. In this series CD19 was highly expressed in MGUS but not in multiple myeloma. Plasma cells bearing this antigen could represent the non-neoplastic process and determination of its expression could be useful for the diagnosis of MGUS.     

Diagnostic and Therapeutic Advances in Blastic Plasmacytoid Dendritic Cell Neoplasm: A Focus on Hematopoietic Cell Transplantation

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an exceedingly rare disorder categorized under acute myeloid leukemia by the World Health Organization. Phenotypically, malignant cells coexpress CD4⁺ and CD56⁺ without coexpressing common lymphoid or myeloid lineage markers. BPDCN frequently expresses CD123, TCL1, BDCA-2, and CD2AP. Restriction of CD2AP expression to plasmacytoid dendritic cells makes it a useful tool to help confirm diagnosis. Clonal complex chromosome aberrations are described in two-thirds of cases. Eighty percent of BPDCN cases present with nonspecific dermatological manifestations, prompting inclusion in the differential diagnosis of atypical skin rashes refractory to standard treatment. Prognosis is poor, with a median survival of less than 18 months. No prospective randomized data exist to define the most optimal frontline chemotherapy. Current practice considers acute myeloid leukemia-like or acute lymphoblastic leukemia–like regimens acceptable for induction treatment. Unfortunately, responses are short-lived, with second remissions difficult to achieve, underscoring the need to consider hematopoietic cell transplantation early in the disease course. Allografting, especially if offered in first remission, can result in long-term remissions. Preclinical data suggest a potential role for immunomodulatory agents in BPCDN. However, further research efforts are needed to better understand BPDCN biology and to establish evidence-based treatment algorithms that might ultimately improve overall prognosis of this disease.     

Plasmablastic lymphoma of the cecum: Report of a case with cytologic findings

Plasmablastic lymphoma (PBL) is a rare lymphoma that is characterized by a diffuse proliferation of large neoplastic cells resembling B immunoblasts, but shows the immunophenotype of plasma cells. PBL is most commonly seen in the oral cavity of human immunodeficiency virus (HIV)‐positive patients. Epstein‐Barr virus (EBV) may be closely related the pathogenesis of PBL. We report a case of HIV‐negative PBL in a 75‐year‐old man without EBV infection. Histologic examination of the cecal tumor following right hemicolectomy and cytologic examination of ascitic fluid were performed. Cytologic specimens were hypercellular and composed of single cells and loosely formed clusters. Large tumor cells showed plasmacytoid features with basophilic cytoplasm, large nuclei, prominent nucleoli, and focal perinuclear halos. Abnormal mitotic figures were easily identified. On immnohistologic study, the tumor cells were positive for CD138 (plasma cell marker) and kappa, but negative for CD45, CD3, CD20, CD79a, CD56, and cyclin D1. The proliferation index (Ki‐67) was high. This is a very rare case of PBL without HIV and EBV infection, involving the cecum. Diagn. Cytopathol. 2011;39:297–300. © 2010 Wiley‐Liss, Inc.     

Extranodal NK/T‐cell lymphoma,nasal type of the uterine cervix: A case report

We report a rare case of extranodal NK/T‐cell lymphoma, nasal type of the uterine cervix that showed cytologic features mimicking cervical cancer. A 65‐year‐old woman presented with vaginal bleeding. Gynecological examination revealed a bulky tumor of the cervix. A conventional Papanicolaou‐stained cervical smear showed hypercellularity consisting of numerous variably sized cohesive clusters that mimicked epithelial tumors, with a necrotic and inflammatory background. A small number of individually scattered cells were also identified. These scattered cells showed pleomorphic, often cleaved, or horseshoe‐shaped nuclei and pale cytoplasm. Biopsy specimens revealed a diffuse growth of atypical cells with an angiocentric pattern. Extensive necrosis and infiltration of inflammatory cells were present. There were numerous mitotic figures. The tumor cells were positive for CD45RO, CD3ε, CD56, granzyme B, TIA‐1, CD7, and Epstein–Barr virus (EBV)‐encoded small RNA (EBER) by in situ hybridization, and negative for cytokeratin, chromogranin A, synaptophysin, CD4, CD5, CD8, CD20, and CD30. Based on these findings, this tumor was diagnosed as extranodal NK/T‐cell lymphoma, nasal type of the uterine cervix. Diagn. Cytopathol. 2016;44:430–433. © 2016 Wiley Periodicals, Inc.     

Immunophenotypic analysis of myeloperoxidase-negative leukemia cutis and blastic plasmacytoid dendritic cell neoplasm

Myeloid leukemia cutis (LC) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are morphologically indistinguishable malignancies that frequently manifest in the skin. Separating myeloperoxidase-negative LC from BPDCN may be particularly challenging. We identified a panel of immunohistochemical stains to distinguish myeloid LC (23 cases) from BPDCN (12 cases): myeloperoxidase, which stained 7 cases (30%) of LC and 0 cases (0%) of BPDCN; CD56, which stained 12 cases (52%) of LC and all 12 cases (100%) of BPDCN; CD4, which stained 2 cases (9%) of LC and all 12 cases (100%) of BPDCN; CD123, which stained 4 cases (17%) of LC and 10 cases (83%) of BPDCN; and Tcl-1, which stained 2 cases (9%) of LC and 9 (82%) of 11 cases of BPDCN. It is interesting that CD33 was not helpful; it stained 18 (78%) cases of LC and 11 cases (92%) of BPDCN. Our results indicate that a panel that includes CD4, CD56, CD123, and Tcl-1 can appropriately distinguish between these 2 entities.     

Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid‐rich hepatocellular carcinoma

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich‐hepatocellular carcinoma (HCC) was challenging. The patient was a 50‐year‐old woman in whom a 3‐cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well‐demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid‐rich type HCC because it stained positive for Hep Par1, but negative for arginase‐1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF‐1 and 3β‐HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase‐1 is to rule out the possibility of lipid‐rich HCC.     

Follicular dendritic cell sarcoma of small intestine with aberrant T-cell marker expression

Follicular dendritic cell sarcoma (FDCS) is an uncommon neoplasia usually occurring in lymphoid tissue. Herein is presented a case of FDCS of the small intestine with positivity for T-cell antigen, simulating T-cell lymphoma. An 82-year-old man consulted a doctor for a 1 week history of epigastric pain. Imaging indicated a mass in the small intestine. Malignant lymphoma was suspected because of high serum levels of soluble interleukin-2 receptor, and resection of the tumor was performed. Microscopically the tumor consisted of large pleomorphic cells with reactive small lymphocytes. Most of the nuclei of the tumor cells were round or ovoid, and some of the tumor cells also had spindle-shaped nuclei. Although the tumor cells were diffusely positive for CD45RO and CD4 on immunohistochemistry, negativity for pan-T-cell markers and CD56 was unusual for T-cell lymphoma of intestinal origin. Additional immunohistochemistry demonstrated that the tumor cells were positive for follicular dendritic cell markers including CD23, CD35 and CAN.42, and diagnosis of FDCS was made. To the authors' knowledge this is the first case of FDCS aberrantly expressing CD45RO; FDCS expressing T-cell markers can be a pitfall for diagnosis of FDCS.     

Fine needle aspiration of primary mediastinal synovial sarcoma: Cytomorphologic,immunohistochemical, and molecular study

The cytologic diagnosis of synovial sarcoma (SS) can be difficult when it occurs in unusual locations, atypical age groups, and/or have unusual morphology. We report a case of primary mediastinal SS in a 65‐year‐old male with a long smoking history who presented with increasing shortness of breath and was found to have a 14.2 cm mediastinal mass. Smears from the endobronchial ultrasound guided fine needle aspiration of the mass were moderately cellular consisting of loosely cohesive clusters, some of which demonstrated nuclear molding, and dispersed single cells. The relatively uniform tumor cells had a high nuclear‐to‐cytoplasmic ratio, finely granular chromatin, and inconspicuous nucleoli. Some of the single cells had spindled morphology with unipolar wispy tails and naked nuclei. Based on the clinical presentation and the cytomorphologic features, our initial differential diagnoses included atypical carcinoid, small cell carcinoma, basaloid squamous cell carcinoma, sarcoma, and lymphoma. Immunohistochemical studies on the cell block sections revealed that the tumor cells were focally positive for cytokeratin and diffusely positive for CD56, while negative for CD45, synaptophysin and chromogranin. Ultimately, an immunohistochemical stain for TLE‐1 demonstrated diffusely strong nuclear positivity and molecular studies showed the presence of the t(X; 18) SYT/SSX1 translocation confirming the diagnosis of SS. In this report, we describe the cytomorphologic features of SS, its diagnostic pitfalls, and potential mimics in the mediastinum. Diagn. Cytopathol. 2014;42:170–176. © 2012 Wiley Periodicals, Inc.