肝脏炎性假瘤与炎性假瘤样滤泡树突状细胞肿瘤的病理学诊断

目的探讨肝脏炎性假瘤及肝脏炎性假瘤样滤泡树突状细胞肿瘤的临床病理学特征及诊断、鉴别诊断要点。方法对肝脏炎性假瘤及肝脏炎性假瘤样滤泡树突状细胞肿瘤各1例进行临床病理分析、免疫组织化学染色及EBV-encoded RNA（EBER）原位杂交检测。结果肝脏炎性假瘤的临床症状包括右上腹不适或疼痛、发热、肝肿大、体重减轻等。大体肿瘤呈实性,境界清楚;镜下肿瘤细胞呈梭形,波浪状排列,其间可见大量淋巴细胞及浆细胞浸润以及散在分布的大的多形性细胞。核仁明显。肝脏炎性假瘤样树突状细胞肿瘤的临床症状、影像学表现及镜下表现均与肝脏炎性假瘤十分相似。但肿瘤细胞边界不清,胞质嗜酸性,除R—S样细胞外,还可见到不少形态怪异的巨细胞,且免疫表型CD21、CD35阳性。EBER（EBV—encoded RNA原位杂交）阳性。结论肝脏炎性假瘤样滤泡树突状细胞肿瘤是罕见的肿瘤,诊断时需注意与肝脏梭形细胞肿瘤甚至霍奇金淋巴瘤鉴别,树突状细胞免疫标记CD21、CD35阳性,特别是EBER原位杂交阳性有助于诊断。     

Esophageal pleomorphic giant cell carcinoma combined with small cell carcinoma

Herein is presented the case of an esophageal pleomorphic giant cell carcinoma combined with small cell carcinoma (SCC). The patient, a 77-year-old man, initially presented with dysphagia and hoarseness, and endoscopy indicated a large esophageal tumor. Despite chemoradiation therapy, the patient died from widespread local extension of the tumor and distant metastases approximately 8 months after onset of the symptoms. Histologically, the primary tumor was composed of pleomorphic tumor components, SCC components, and a tiny focus of squamous cell carcinoma. The pleomorphic tumor cells, consisting of solid sheets of poorly cohesive epithelioid cells and numerous multinucleated giant cells with abundant eosinophilic cytoplasm, were immunohistochemically positive for vimentin and desmin, with scattered positivity for epithelial membrane antigen (EMA) and neuron-specific enolase (NSE), but negative for myoglobin. These findings were histopathologically compatible with pleomorphic giant cell carcinoma occurring at other sites such as the lung. SCC cells, morphologically similar to their pulmonary counterpart, were positive for EMA and some neuroendocrine markers such as chromogranin A and NSE, and occasionally positive for vimentin and desmin. Esophageal pleomorphic giant cell carcinoma can occur in close association with SCC, and should be included in the differential diagnosis of esophageal tumors showing pleomorphism.     

Follicular dendritic cell sarcoma presenting as a submucosal tumor of the stomach

Follicular dendritic cell (FDC) sarcomas, especially those of extranodal origin, are extremely rare, and this entity could easily be missed without a high index of suspicion. We report a case of FDC sarcoma presenting as a submucosal tumor of the stomach in a 45-year-old man. The mass was a spindle and epithelioid mesenchymal tumor with many individually scattered and perivascular aggregates of lymphocytes. Immunohistochemical and ultrastructural studies confirmed the diagnosis. Although more than 50 cases of this tumor have been documented in the English literature, to our knowledge the presentation of FDC sarcoma as a submucosal tumor of the stomach has never been recorded. This case highlights the occurrence of FDC sarcoma as a submucosal tumor of the gastrointestinal tract. We believe that FDC sarcoma should be included in the differential diagnosis of spindle or epithelioid cell tumors of the gastrointestinal hollow viscus to prevent this still under-recognized tumor from being overlooked.     

Primary hepatic lymphoma with spindle cell components: a case report

Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.     

Multiple giant angiomyolipomas with a polygonal epithelioid cell component in tuberous sclerosis: An autopsy case report

A recent case of angiomyolipoma (AML) with a prominent Component of polygonal epithelioid cells is described. A 27-yearoid Japanese male with tuberous sclerosis presented with massive abdominal tumors increasing progressively in size. The patient died of respiratory disturbance and the autopsy revealed massive tumors in the bilateral kidneys, liver and lymph nodes, subependymal giant cell glioma of the brain and lymphangiomyomatosis of the lungs. The giant tumors were an unusual type of AML with a component of polygonal epithelioid cells, which showed a hepatocel-lular carcinoma-like pattern in some areas. Smooth muscle components comprising spindle cells, short or plump spindle cells and polygonal epithelioid cells frequently exhibited positive staining for HMB-45 but negative staining for epithelial cell markers. The unusual AML presented in this case was thought to be of low-grade malignancy and slow growing. it has been suggested that angiomyollpomas with diffuse areas of epithelioid cell component are potentially malignant. Immunostalnings positive for HMB-45 but negative for epithelial cell markers are considered to be useful in differentiating AML with polygonal epithelioid cell component from other tumors, especially from renal cell carcinoma and hepatocellular carcinoma.     

Combined hepatocellular carcinoma and osteoclast-like giant cell tumor of the liver: Possible clue to histogenesis

Hepatic giant cell tumor is extremely rare, and only five cases have been reported of overt hepatocellular carcinoma, thus its histogenesis is controversial. Herein is reported a case of simultaneous hepatocellular carcinoma and osteoclast-like giant cell tumor in a single tumor. A liver tumor was found in a 74-year-old woman. Histologically the tumor consisted of two distinct components: mononuclear and multinuclear giant cells with osteoclastic giant cells, and a conventional hepatocellular carcinoma. The boundary between the two components showed transitional features. Immunohistochemistry showed that the osteoclast-like giant cells were CD68 and vimentin positive, but cytokeratin and AFP negative, while spindle-shaped cells were positive only for vimentin. In a portion of the hepatocellular carcinoma the cells were cytokeratin-8 and AFP positive. Ki-67 positivity was 10% for the hepatocellular carcinoma, 60% for the spindle-shaped cells, and 0% for the giant cells. It is possible that the tumor might have had a hepatocellular carcinoma origin, given the more highly proliferative sarcomatous changes and reactive osteoclast-like cells. This case provides a clue to the histogenesis of hepatic giant cell tumors.     

Reticulum cell sarcoma of lymph node with mixed dendritic and fibroblastic features.

We report a case of clinically aggressive reticulum cell sarcoma with mixed follicular dendritic cell (FDC) and fibroblastic reticular cell (FRC) features. Histologically, the tumor was confined to lymph nodes occurring as a multifocal epithelioid and spindle cell proliferation with appreciable mitotic rate and numerous admixed non-neoplastic B-cells. Ultrastructural examination revealed elongated cells with prominent nucleoli, interdigitating cell processes and frequent desmosomes. These features are typical of FDC sarcoma. However, immunohistochemical stains showed no expression of antigens characteristic of FDCs, including CD21, CD23 and CD35. Cytogenetic characterization of this tumor, by conventional G-banding and multicolor spectral karyotyping, revealed multiple clonal chromosomal aberrations, including del(X)(p11.4) and add (21)(p11.2). Gene expression analysis by cDNA microarray of RNA obtained from short-term tumor cultures revealed high-level expression of a set of genes (including PDGF receptor-alpha and -beta, certain metalloproteinases, and CD105) that were also highly expressed in cultures of nodal FRC cultured from non-neoplastic lymph nodes. We propose that this tumor represents a nodal sarcoma with intermediate differentiation between FDCs and FRCs. This case adds to the diversity of tumors that may arise from lymph node stroma and supports a possible relationship between the FDC and FRC lineages.     

Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors

Podoplanin, recognized by monoclonal antibody D2-40, may be a useful marker for follicular dendritic cell (FDC) tumors. Paraffin sections of 125 dendritic cell, histiocytic, and spindle cell lesions were studied, including 11 FDC tumors, 5 interdigitating dendritic cell tumors, 10 histiocytic sarcomas, 5 Langerhans cell histiocytosis, 5 sinus histiocytosis with massive lymphadenopathy, 5 inflammatory pseudotumors of lymph node or spleen, 9 nodal Kaposi sarcomas, 6 inflammatory myofibroblastic tumors (IMTs), 29 gastrointestinal stromal tumors (GISTs), and 10 cases each of malignant peripheral nerve sheath tumor, leiomyosarcoma, monophasic synovial sarcoma (SS), and solitary fibrous tumor. All FDC tumors and Kaposi sarcomas showed strong immunoreactivity for podoplanin (predominantly membranous). Podoplanin expression was only occasionally observed in the other tumor types, including 7 GISTs (24%), 2 IMTs (33%), and 3 SS (30%), and was generally weak and cytoplasmic. Reactivity for podoplanin was more common in spindle cell GISTs (5/13 [38%]) than in epithelioid or mixed-type GISTs (2/16 [13%]). Podoplanin is a highly sensitive marker for FDC tumors and may be useful to help confirm the diagnosis in conjunction with conventional FDC markers, particularly in the differential diagnosis of dendritic cell and histiocytic lesions.     

Clinicopathological characteristics of kidney mucinous tubular and spindle cell carcinoma

Kidney mucinous tubular and spindle cell carcinoma (MTSpCC) is a rare renal low-grade pleomorphic epithelial neoplasm featured by tubular and spindle cells with a relatively indolent behavior. This study was designed to clinicopathologically characterize two cases of kidney MTSpCC. Similar to other tumors, the data showed the diagnosis of MTSpCC relies on histological examination. Tumor cells stained strongly for CK19, CK20, and CK7 within the epithelioid component. Whereas evaluating MTSpCC clinically showed no specific symptoms, analyzing MTSpCC microscopically showed multiple elongated tubular branches of tumor cells that are closely arranged in cord-like manner under lightly stained myxoid stroma. MTSpCC also has the spindle cell area; the single tumor cell is small and nucleus round or oval. Immunohistochemical analysis of cytokeratins, electron microscopy, or genetic tests all improves the diagnosis.     

Clinicopathologic characteristics of inflammatory pseudotumor-like follicular dendritic cell sarcoma

Inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a recently described rare tumor and considered a unique entity, with different histologic appearances and behavior from those of the classical FDC sarcoma. This study analyzed the clinical and pathological findings of two such cases that the authors encountered and 36 previously reported cases identified in the literature. Assessment of all 38 cases showed a slight female predominance (2.2:1) with a median age of 56.5 years. Seventeen patients complained of abdominal discomfort or pain, while fifteen patients had no clinical symptom. Almost all cases occurred in liver (n = 20) or spleen (n = 17). Except in one case, all patients underwent surgical resection of the tumor alone. Histologic features showed a mixture of chronic inflammatory cells and variable amounts of spindle cells with vesicular nuclei and distinct nucleoli. The tumor cells expressed conventional FDC markers such as CD21 (75%), CD35 (92%), CD23 (62%), clusterin (75%), and CNA.42 (100%). EBV was detected in thirty-five cases (92.1%) by Epstein-Barr virus (EBV)-encoded RNA in situ hybridization, and EBV-latent membrane protein-1 was expressed in 90% of the cases. With a median follow-up of 21 months, 29 patients (85.3%) were alive and well, 4 (11.8%) were alive with disease, one patient (2.9%) died of disease. Only four patients with hepatic tumors underwent recurrence or metastasis after initial treatment. Epstein-Barr virus is thought to play a role in the development of the tumor; however, the pathogenesis of the disease and the origin of tumor cells remain unclear.     

Follicular dendritic cell tumor of the gastrointestinal tract: Report of a rare neoplasm and literature review

Follicular dendritic cell (FDC) tumor is a rare neoplasm of the accessory immune system showing FDC differentiation. Histologically, a conventional type and an inflammatory pseudotumor (IPT-like) type are recognized. The etiology of FDC tumor is unknown. While rare FDC tumors were associated with hyaline-vascular Castleman's disease (HVCD), hepatosplenic IPT-like FDC tumors consistently harbor EBV infection. FDC tumors of the gastrointestinal (GI) tract and mesentery/omentum are exceedingly rare, with only 17 cases reported so far. We report an additional case of an IPT-like FDC tumor of the ileum and mesentery in a 52-year-old schizophrenic man. The tumor consisted of highly atypical multinucleated giant cells in a background of intense lymphoid infiltrate with prominent eosinophilia reminiscent of Hodgkin's lymphoma. Tumor cells were immunoreactive for vimentin, CD21, CD35, fascin, smooth muscle actin and CD68, but were negative for all lineage-specific lymphoreticular, myeloid, mesenchymal and epithelial markers. Immunostaining for HHV-8 and in situ hybridization for EBV-encoded RNA (EBER) were negative. Some mesenteric lymph nodes showed HVCD-like changes. The differential diagnostic considerations of this unusual and rare neoplasm, mainly lymphocyte-rich GI stromal tumor (GIST), malignant lymphoma and inflammatory neoplasia of diverse histogenetic types, will be discussed together with a literature review on gastrointestinal FDC tumors.     

Fine needle aspiration biopsy of renal mucinous tubular and spindle cell carcinoma: Report of two cases

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal tumor. Here we report two cases of MTSCC which were initially evaluated by fine needle aspiration biopsy (FNAB) and followed by surgical resection of the tumors. The cytomorphologic features of MTSCC were characterized by aggregates of relatively uniform, predominantly oval to spindle cells intermixed with abundant metachromatic myxoid matrix. Only rare epithelioid tumor cells with vacuolated cytoplasm were present. Immunohistochemically, the tumor cells were positive for CK7, CK19, CD10, vimentin, E‐cadherin, alpha‐methyl CoA racemase, and negative for CK903 and CK20. EMA and carbonic anhydrase IX immunoreactivity was seen in one of the two cases. Multiple chromosomal losses involving chromosomes 1, 2, 17 and likely chromosome 7 were revealed by fluorescence in situ hybridization (FISH). These cytomorphologic, immunophenotypic, and cytogenetic features were helpful for including this entity in the differential diagnosis of renal cell carcinomas. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and tumors of skin, brain, heart, and kidney. In this study, we focused on two of the most frequent tumors in TSC patients, renal angiomyolipomas and subependymal giant cell astrocytomas (SEGAs). Two questions were addressed. First, is loss of tuberin, the product of the TSC2 gene, seen in both renal and central nervous system tumors from TSC patients? Second, when loss of tuberin occurs, does it affect each of the cell types seen in these tumors? We used a loss of heterozygosity approach to identify tumors from TSC2 patients. We found loss of tuberin immunostaining in the spindle and epithelioid cells but not in the giant cells of six TSC2 SEGAs. We also found loss of tuberin immunostaining in all three cell types (smooth muscle, fat, and vessels) of six TSC2 angiomyolipomas. Chromosome 16p13 loss of heterozygosity occurred in both spindle and epithelioid cells of a SEGA and in smooth muscle and fat but not the vessels of two angiomyolipomas. These results support a two-hit tumor suppressor model for the pathogenesis of SEGAs and angiomyolipomas. The vascular elements of angiomyolipomas and the giant cells of SEGAs may be reactive rather than neoplastic.     

Primary mediastinal giant cell tumors: a clinicopathologic and immunohistochemical study of two cases

Two cases of posterior mediastinal giant cell tumors are presented. The patients are a woman and a man, 31 and 18 years old, respectively. One of the patients had symptoms of paresthesias while the other was completely asymptomatic. Complete physical examination did not disclose evidence of tumor elsewhere. Neither patient had a previous history of malignancy. Surgical resection was performed. Histologically, both tumors were composed of a proliferation of osteoclast-like giant cells associated with a mononuclear cell population composed of oval and spindle cells. Mitotic activity and mild cellular atypia were present in the mononuclear cell component. No evidence of necrosis or hemorrhage could be demonstrated in either case. Immunohistochemically, both tumors showed strong positive reaction in the mononuclear component for antibodies against vimentin and CD68, while keratin, epithelial membrane antigen, CD45, S-100 protein, and desmin were negative. On clinical follow-up, both patients are alive and well without evidence of recurrence or metastasis 6 and 108 months after surgery. The present cases highlight the ubiquitous distribution of soft tissue giant cell tumors and the importance of considering these tumors in the differential diagnosis of posterior mediastinal neoplasms.     

Follicular dendritic cell sarcoma of the spleen

Diagnosis of primary spindle cell tumors of the spleen is challenging because of the limited immunologic and cytogenetic characterization of this rare entity. We report a case of primary follicular dendritic cell (FDC) sarcoma of the spleen in a 44-year-old woman. Indications for FDC included positive staining for CD21, Ki-M4P, CD14, and fascin. Expression of both standard FDC markers CD23 and CD35 was detected immunohistochemically using tyramide signal amplification. Cytogenetic analysis revealed multiple clonal chromosomal aberrations involving unbalanced translocations of chromosomes X, 3, 5, 7, 8, 9, and 10, leading to net gains at 3q, 7p, 8q, and 9q and net losses at Xp, 8p, 9p, and 10p. Loss at Xp has been described previously in another tumor with FDC features, suggesting that this aberration might play a common role in this malignancy.     

Giant-cell containing neoplasms of the pancreas: an aspiration cytology study

Giant-cell containing neoplasms of the pancreas are rare with few reports documenting their cytologic appearance. Giant-cell containing neoplasms of the pancreas have been divided into two subtypes corresponding to the osteoclastic giant-cell tumor of the pancreas and the pleomorphic giant-cell carcinoma of the pancreas. Despite the better prognosis reported in some series for osteoclastic giant-cell tumors, the most recent edition of the World Health Organization classification lumps the two entities into a single category designated as undifferentiated carcinoma with osteoclast-like giant cells. Smears obtained from osteoclastic giant-cell tumors show numerous giant-cells with clustered overlapping, bland appearing nuclei containing prominent nucleoli consistent with an osteoclast-type multinucleated giant-cell. These neoplasms contain a second population of mononuclear cells showing more marked nuclear atypia. Pleomorphic giant-cell carcinomas are characterized by anaplastic giant-cells displaying marked nuclear pleomorphism. The mononuclear component is also pleomorphic with markedly atypical epithelioid and spindle shaped cells. In three reported cases, a tumor contained a mixture of the two cell patterns. Thus, undifferentiated carcinoma with osteoclast-like giant cells and pleomorphic giant cell carcinoma may represent a morphologic spectrum with pure osteoclast-like giant-cell tumors at one end and pleomorphic giant-cell carcinoma at the other. Fine-needle aspiration specimens from pure osteoclast-like giant-cell tumors will contain a population of bland multinucleated osteoclastic-like giant-cells that differ markedly from the anaplastic giant-cells of pleomorphic giant-cell carcinoma. The difference in the appearance of the giant-cells aids in distinction of the two neoplasms. When in pure form, the two neoplasms may follow different clinical courses.     

Mediastinal follicular dendritic cell sarcoma involving bone marrow: a case report and review of the literature

We report a rare case of mediastinal follicular dendritic cell (FDC) sarcoma involving the bone marrow. The patient, a 46-year-old woman, had a clinically aggressive tumor in the anterior mediastinum that was initially diagnosed as a diffuse B-cell lymphoma. She received chemotherapy but showed no significant improvement. One year later, the patient presented at our institution with pelvic bone metastases. Biopsy specimens of the sacrum lesion and bone marrow were obtained. The diagnosis of FDC sarcoma was made based on histological examination and immunohistochemical findings, including strong positive staining of tumor cells for CD21, CD23, clusterin, and epidermal growth factor receptor (EGFR) and negative staining for CD20, CD30, CD45, CD1a, S-100, vimentin, and keratin cocktail. Histological examination and immunohistochemical studies of a previous biopsy of the mediastinal mass confirmed the diagnosis of mediastinal FDC sarcoma. The patient was treated with an appropriate chemotherapy regimen; 1 month later, follow-up bone marrow biopsy revealed no tumor cells. Although FDC sarcoma is considered a low-grade tumor, the tumor in the present case not only developed at an unusual location with bone metastasis but also involved bone marrow. To our knowledge, this is the first such case ever reported. This case also highlights the utility of EGFR as an immunohistochemical marker of dendritic cell tumors that could be used as a diagnostic tool and guide for choosing appropriate chemotherapy regimens.