Pleomorphic carcinoma with osteoclastic giant cells of the breast: Immunohistochemical differentiation between coexisting neoplastic and reactive giant cells

Herein is described a unique case of breast carcinoma with two different types of giant cells noted in both cytological and histological specimens. A 51-year-old Japanese woman noticed a hard mass in the upper outer quadrant of her left breast. Aspiration cytology exhibited numerous anaplastic giant cells; the cytological diagnosis was high-grade ductal carcinoma, although a few osteoclastic giant cells were also observed. A left simple mastectomy and sentinel lymph node biopsy were performed. Histologically, approximately 90% of the tumor was composed of giant cells; conventional invasive ductal carcinoma and ductal carcinoma in situ were found focally at the periphery of the tumor. The main part of the tumor contained both anaplastic, neoplastic giant cells and non-neoplastic, osteoclastic giant cells that were distinguishable from nuclear atypism. The presence of the two types of giant cells was also confirmed on immunohistochemistry using a histiocytic marker (CD68) and two epithelial markers (AE1/AE3 and CAM5.2). Based on the latest World Health Organization classification, the diagnosis was pleomorphic carcinoma with osteoclastic giant cells. To the authors' knowledge there has been no previous report on this subject except for a single case mentioned in Rosen's Breast Pathology .     

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.     

Ductal adenocarcinoma of the pancreas with huge cystic degeneration: a lesion to be distinguished from pseudocyst and mucinous cystadenocarcinoma

Cystic neoplasms of the pancreas are rare and often mistaken for pseudocyst by imaging studies and macroscopic examination. We describe an unusual tumor of the pancreas composed of a mural nodule of anaplastic carcinoma arising from a huge ductal adenocarcinoma undergoing cystic degeneration. The cyst measured 27 x 13 x 4 cm. Light microscopy showed that the cyst was partly lined by a single layer of cuboidal to columnar tumor cells with focal mucin production and was surrounded by hyalinized connective tissue. Most lining epithelial cells were absent owing to extensive degenerative process. Immunohistochemical studies showed positive staining of cytokeratin and vimentin for pleomorphic giant tumor cells, which were negative for leukocyte common antigen (CD45), KP-1 (CD68), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA). The ductal adenocarcinoma stained strongly positive for cytokeratin and EMA, and negative for vimentin, CD45, CD68, and CEA. The clinical course of the current case was extremely poor and the prognosis resembled that of an anaplastic carcinoma. Therefore, we like to emphasize the importance of complete excision and extensive sampling of any cystic neoplasms in the pancreas including those with large cystic component to avoid missing the malignant elements.     

Invasive breast carcinoma with features of neuroendocrine carcinoma and carcinoma with osteoclastic cells: fine-needle aspiration cytology and histology of two cases

We report two cases, with overlapping cyto-histological characteristics, of invasive neuroendocrine carcinoma of the breast with associated stromal features distinctive of carcinoma with osteoclastic giant cells. Fine-needle aspiration cytology showed monomorphic, medium-sized, mildly atypical neoplastic cells, with interspersed multinucleated giant cells and lympho-histiocytic components; hemosiderin deposits were also appreciable. Macroscopic features were typical of invasive carcinoma, but with unusual brown staining. Light microscopy revealed moderately differentiated invasive carcinoma mainly composed of solid sheets of round to polygonal medium-sized cells with a tendency to produce peripheral palisading (carcinoid-like morphology); osteoclast-like multinucleated giant cells, lymphocytes and histiocytes were dispersed only among tumour cells in the distinctive stroma of the carcinoma with osteoclastic giant cells; this stroma was characterised by reactive/fibroblastic features, hypervascularization, extravasated blood cells and hemosiderin deposits that gave rise to the typical staining seen macroscopically. Immunohistochemically, cancer cells were diffusely positive for the neuroendocrine marker synaptophisin with partial chromogranin and NSE staining; the ostoclastic giant cell and histiocyte component were strongly positive for CD68. Both cases also had lymph node metastases; the epithelial neoplastic cells, with regards to neuroendocrine markers, were overlapping to the primitive tumour, the histiocytic/giant cell component appeared present, although with a lower degree, while the distinctive stroma was absent. Breast neuroendocrine carcinomas, associated with multinucleated giant cells and stroma typical of the carcinoma with osteoclastic-like cells, to our knowledge, have not been reported.     

Pleomorphic carcinoma of the large intestine

Pleomorphic carcinoma, firstly described in the lung, is exceptional in the digestive tract. This tumor is often associated with fever and peripheral blood leukocytosis. The histological feature is characterized by giant pleomorphic often multinucleated cells with dense neutrophil infiltration and frequent phagocytosis of neutrophils by the tumor cells. Expression of epithelial markers confirm the diagnosis. The prognosis is very poor. We hereby report one case of pleomorphic carcinoma unusually situated in the large intestine, emphasizing difficulties encountered in establishing diagnosis.     

Abnormal Nuclear Structures (Micronuclei,Nucleoplasmic Bridges,and Nuclear Buds) in a Pleomorphic Giant Cell Carcinoma of the Stomach

A rare case of pleomorphic giant cell carcinoma of the stomach in a 70-year-old man is reported. Characteristic microscopic findings included a general lack of architectural cohesiveness, aggregates of mononucleated or multinucleated giant cells, extensive areas of coagulative necrosis, and numerous mitoses. Immunohistochemically, tumor cells displayed cytoplasmic immunoreactivity for cytokeratin AE1/AE3 as well as overexpression of p53 and Ki-67. Electron microscopy revealed paranuclear tonofilaments bundles in giant cells confirming their epithelial nature. Furthermore, giant cells contained two or more nuclei with heterogeneous size, nucleoplasmic bridges, nuclear buds, and micronuclei. Similar abnormal nuclear structures have been closely related to breakage-fusion-bridge type of mitotic disturbances in tumor cell lines, and have not been previously reported in a human tumor.     

Abnormal nuclear structures (micronuclei, nucleoplasmic bridges, and nuclear buds) in a pleomorphic giant cell carcinoma of the stomach

A rare case of pleomorphic giant cell carcinoma of the stomach in a 70-year-old man is reported. Characteristic microscopic findings included a general lack of architectural cohesiveness, aggregates of mononucleated or multinucleated giant cells, extensive areas of coagulative necrosis, and numerous mitoses. Immunohistochemically, tumor cells displayed cytoplasmic immunoreactivity for cytokeratin AE1/AE3 as well as overexpression of p53 and Ki-67. Electron microscopy revealed paranuclear tonofilaments bundles in giant cells confirming their epithelial nature. Furthermore, giant cells contained two or more nuclei with heterogeneous size, nucleoplasmic bridges, nuclear buds, and micronuclei. Similar abnormal nuclear structures have been closely related to breakage-fusion-bridge type of mitotic disturbances in tumor cell lines, and have not been previously reported in a human tumor.     

Pleomorphic carcinoma of breast: a case report and review of literature

Pleomorphic carcinoma of the breast is a rare variant of invasive breast carcinoma. Here, we report a case in a 45-year-old woman presenting a lesion composed microscopically of predominantly pleomorphic giant cells, squamous metaplastic component and focal conventional ductal carcinoma. Immunohistochemical assay showed different immunologic manifestation in respective malignant components. Despite positive lymph node metastasis, the patient has been well without evidence of recurrence or metastasis two years after operation. The implication of this report is to provide insights into further understanding of this rare tumor with review of the literature.     

Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung

Giant cell carcinoma (GCC) is a highly aggressive variant of sarcomatoid carcinoma of the lung. To date, however, there have been no reported cases of ovarian carcinoma mainly composed of GCC. Herein is reported the case of a 54-year-old Japanese woman with an undifferentiated ovarian carcinoma producing granulocyte colony-stimulating factor (G-CSF) and an inflammatory cytokine. Histologically, the tumor was composed of cohesive nests or discohesive pleomorphic mononucleated or multinucleated tumor giant cells, accompanied by inflammatory cell infiltration and emperipolesis. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen and cytokeratin 7. Clinically, after the initial surgery, the tumor had rapid regrowth along with the production of G-CSF and an inflammatory cytokine. Adjuvant chemotherapy was administered but induced severe heart failure and severe neutropenia, probably due to the presence of hypercytokinemia and excess G-CSF. Upon the appearance of these fatal side-effects the chemotherapy was immediately discontinued and replaced with radiotherapy. The recognition of this type of ovarian tumor is important for clinical management, because adjuvant chemotherapy is the standard treatment for clinical management of epithelial ovarian cancer.     

The majority of triple-negative breast cancer may correspond to basal-like carcinoma,but triple-negative breast cancer is not identical to basal-like carcinoma

Recently, the concept of basal-like carcinoma has been proposed. However, there are only a few reports about the relationship between triple-negative cancer and basal-like carcinoma. In this article, we report the study of the expression of basal cell markers in 11 triple-negative cancers. Eight tumors (4 metaplastic carcinomas, 2 invasive ductal carcinomas, 1 invasive papillary carcinoma, and 1 medullary carcinoma) were positive for more than three markers among cytokeratins 5, 14, and 17, and p63. Three tumors (2 invasive ductal carcinomas and 1 apocrine carcinoma) were completely negative for all markers. Among 8 tumors positive for basal markers, cytokeratins 5 and 17 were expressed in all 8 tumors, cytokeratin 14 in 6 tumors, and p63 in 7 tumors. Finally, we conclude that the majority of triple-negative cancer may correspond to basal-like carcinoma, but the two entities are not identical. The use of combination immunohistochemistry including cytokeratins 5, 14, and 17 and p63 may contribute to the detection of basal-like carcinoma.     

Osteoclast-like giant cell tumour of the pancreas presenting as a pseudocyst-like lesion

 A 57-year-old male patient presented with a cystic lesion in the tail of the pancreas, which was considered to be a pseudocyst. He was treated by cystojejunostomy but one year later a tumour was found to have invaded the stomach and jejunum. This was an osteoclast-like giant cell tumour containing a small area of typical ductal adenocarcinoma. Immunohistochemical staining revealed that the pleomorphic tumour cells were positive for cytokeratin, epithelial membrane antigen, vimentin and the proliferation marker MIB-1. The osteoclast-like giant cells and some small histiocytic cells stained for leukocyte common antigen and histiocytic markers and were negative for MIB-1. At autopsy, tumour rests were found in the pancreas but there were no metastases. Osteoclast-like giant cell tumours of the pancreas may present as cystic lesions and should be included in the differential diagnosis of pseudocysts. Received: 19 December 1996 / Accepted: 20 March 1997     

含破骨巨细胞样细胞的胰腺多形性癌1例及文献复习

目的 探讨含破骨巨细胞样细胞的胰腺多形性癌的临床病理特征。方法 对1例含破骨巨细胞样细胞的胰腺多形性癌进行临床、病理组织学和免疫组织化学观察。结果 患者为58岁女性，因中上腹部持续性隐痛2个月余就诊，B超、CT检查发现胰腺占位。切除标本示实性结节状肿块，灰白、灰黄色，存灶性坏死。镜下见肿瘤由低分化腺癌伴梭形肉瘤样细胞构成，两种细胞均示CK、Vim、α-AT阳性。可见多灶性巨细胞瘤样结构，由单核瘤细胞和形态上良性的破骨巨细胞样细胞构成；前者见CK散在阳性，Vim和α-AT阳性；后者仅见CD68和Vim阳性。结论 含破骨巨细胞样细胞的胰腺多形性癌是多形性胰腺癌的一种亚型，破骨巨细胞为反应性细胞，非肿瘤成分。     

Histiocytic sarcoma - a case with evenly distributed multinucleated giant cells

Histiocytic sarcoma is an uncommon neoplasm of mature histiocytes with a poor clinical outcome. We report a case of a true histiocytic sarcoma with prominent and evenly distributed multinucleated giant cells that mimics a giant cell tumor of soft tissue. The tumor was located between the appendix, right ovary, and the terminal ileum with severe adhesion. The liver and spleen were not enlarged. Grossly, the tumor appeared grayish white, solid, and soft. Microscopically, polygonal mononuclear tumor cells aggregated to form somewhat epithelioid nests, which occasionally showed coagulative necrosis. Prominent and evenly scattered giant cells were present in all sections. In addition, tumor cell infiltration was noted in regional lymph nodes. The tumor cells were positive for lysozyme, CD68, CD163, and negative for T- and B-cell lineage markers, follicular dendritic cell, megakaryocytic, epithelial, muscular, and melanocytic markers, CD1a and CD30. This case posed great difficulty in clinical and pathological diagnoses. Gross pictures, microscopic findings, and extensive immunostains are important for the differential diagnosis.     

Metaplastic carcinoma with extensive chondroid differentiation in the breast (chondroid carcinoma)

Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.     

Soft-tissue osteosarcoma with prominent aneurysmatic bone cyst-like features: a case report

We describe the cytological features of a soft-tissue high-grade spindle and pleomorphic sarcoma. The smears showed hypercellularity composed of pleomorphic round and elongated cells, and a striking population of multinucleated osteoclast-type giant cells. Microscopically the tumor showed multiple patterns such as highly cellular pleomorphic, less cellular, and hyalinized areas with neoplastic cartilage and osteoid, and areas with hemorrhage and multicystic appearance with numerous osteoclastic giant cells, resembling aneurysmal bone cysts. Immunohistochemical studies showed positivity for vimentin, while chondroid tissue was positive for S-100, and osteoclastic giant cells stained positively for CD68. Due to the varied microscopic patterns, the differential diagnosis included many tumors containing osteoclastic giant cells and osteochondroid tissue.     

Undifferentiated pancreatic carcinoma with osteoclast-like giant cells: Report of a case with osteochondroid differentiation

We report a case of an undifferentiated pancreatic carcinoma with osteoclast-like giant cells with focal osteochondroid differentiation in a 66-year-old man, who presented with painless jaundice, pruritis, and weight loss. Imaging studies revealed an inhomogeneous mass in the head of the pancreas. A pylorus preserving pancreaticoduodenectomy was performed. The resection specimen revealed a 9.5×4.2×3.2 cm³ solid neoplasm in the pancreatic head with direct extension into duodenum and common bile duct. Microscopy showed a cellular neoplasm composed of pleomorphic mononuclear cells (pancytokeratin, and EMA-positive; LCA, and CD68 negative) and osteoclast-like multinucleated giant cells (vimentin, LCA, and CD68-positive; pancytokeratin, and EMA-negative) consistent with OGTP. The tumor contained a focal area of osteochondroid differentiation. Evidence supports that the tumor giant cells are non-neoplastic and of histiocytic origin. Osteochondroid differentiation within undifferentiated carcinoma is unusual; its presence might suggest a sarcoma diagnosis on biopsy material.     

Pleomorphic carcinoma of the breast in a 17-year-old woman

We report a 17-year-old woman with refractory high-grade breast cancer who died early after surgery, with reference to the histogenesis of the cancer. Macroscopically, the tumor was cystic, composed of a mixture of solid and myxomatous areas. Histologically, the tumor exhibited ductal structures and areas with squamoid features. Cancer cells were markedly atypical and polymorphic, and included a mixture of bizarre and eosinophilic cells with rhabdoid feature-like free cells. Immunohistochemically, cytokeratin (CK) 8, CK 18, 34betaE12, CD10, involucrin, CK14, and vimentin were partially positive, whereas estrogen and progesterone receptors and HER-2 were negative. These findings suggest an undifferentiated cancer whose cells have multilineage potential to differentiate into mesenchymal, basal, and squamoid cells, and it was diagnosed as pleomorphic carcinoma, which is a histological type hitherto unreported in young girls. The cancer was refractory to treatment, and the patient died 1 year and 5 months after surgery despite chemotherapy and radiotherapy.     

Mixed germ cell tumor with embryonal carcinoma, choriocarcinoma, and epithelioid trophoblastic tumor in the ovary of a cynomolgus monkey

A seven-year-old female cynomolgus monkey had a mass in the left ovary with metastasis to the lung and the right ovary. The mass of these organs showed three different characteristics, and its immunohistochemical profiles were consistent with embryonal carcinoma (EC), choriocarcinoma (CC), and epithelioid trophoblastic tumor (ETT). The EC was characterized with sheets and glandlike structures with large pleomorphic, single-nucleated epithelial cells that were immunohistochemically positive for α-fetoprotein, octamer-4, and CD30, and with multinucleated giant cells resembling syncytiotrophoblasts. The CC also represented biphasic proliferation of the cytotrophoblast positive for cytokeratin 7 (CK7), which showed negative immunoreactivity for all three of the above antibodies, and it was syncytiotrophoblast positive for human chorionic gonadotropin. The ETT showed numerous floating cells in an abundant eosinophilic extracellular matrix with vacuolated or eosinophilic cytoplasm and was immunohistochemically positive for CK7, p63, and α-inhibin, which features nodule or cordlike structures. Collectively, this neoplasm was identified as a mixed germ cell tumor with EC, CC, and ETT. To our knowledge, this is the first report of EC in nonhuman primates as a component of mixed germ cell tumor.     

Malignant diffuse-type tenosynovial giant cell tumor of the buttock

Malignant diffuse-type tenosynovial giant cell tumor (D-TSGCT) is an unusual sarcoma. We report a case of malignant D-TSGCT located in the left buttock. A 58-year old woman noticed a small mass at her left buttock 3 months previously. The mass tended to enlarge rapidly, and became 6 cm in diameter. Tumor resection was performed. Grossly, the tumor showed a solid growth pattern and whitish appearance with hemorrhage and necrosis. Microscopically, the tumor was composed of a proliferation of short spindle and oval mononucleated cells with numerous osteoclast-like multinucleated giant cells, which occasionally showed coagulative necrosis. In addition, tumor cells had high mitotic activity and atypical mitoses. Immunohistochemically, the mononucleated cells were positive for CD163 and focally positive for CD68 (clone KP-1 and PG-M1), CD4, smooth muscle actin and S100 protein. Osteoclast-like multinucleated giant cells were positive for CD68 (clone KP-1 and PG-M1) and CD4. Pulmonary metastases were found 6 months after the operation. These findings indicate that this lesion is consistent with malignant D-TSGCT.     

Fine-needle aspiration biopsy of pleomorphic (giant cell) carcinoma of the pancreas. Cytologic, immunocytochemical, and ultrastructural findings

Four cases of pleomorphic (giant cell) carcinoma (PGC) of the pancreas, diagnosed by fine-needle aspiration biopsy, are presented. Ancillary immunocytochemical studies were also performed on the smears (four cases) and cell blocks (three cases), along with ultrastructural (electron microscopic) examination of the aspirated specimen (two cases). Three of the four patients were elderly (age range: 44-65 years), and all had large pancreatic masses. A spectrum of cytomorphologic features was encountered, including poorly cohesive bizarre mononuclear cells, many multinucleated tumor giant cells, and associated malignant spindle cells. Prominent cellular cannibalism and cytophagocytosis also were seen. Immunoperoxidase studies demonstrated dual staining of the malignant cells for cytokeratin and vimentin in two cases and exclusive staining for vimentin in the remaining two cases. Ultrastructural examination demonstrated epithelial features in both cases studied. One of the cases demonstrated intracytoplasmic whorled bundles of intermediate filaments, corresponding to pale eosinophilic globular material, appreciated both in the Diff-Quik- and Papanicolaou-stained smears and staining with positive results for vimentin. The immunocytochemical studies suggest that the coexpression of vimentin and cytokeratin within the cells is consistent with a pleomorphic malignancy of epithelial origin. It is speculated that the staining of two of the cases exclusively for vimentin can be seen in either epithelial malignancies with sarcomatoid transformation or, less likely, a pure sarcoma of the pancreas.