Undifferentiated carcinoma of the lung with osteoclast-like giant cells

We treated a patient with undifferentiated carcinoma of the lung, with osteoclast-like giant cells resembling those of the giant cell tumor of bone. The clinical and morphologic characteristics of this case are documented, and the literature concerning this type of tumor is reviewed. The tumor differed histologically from the pleomorphic carcinoma, which occurs most commonly in the lung, and showed diverse pleomorphic manifestation with benign looking osteoclast-like multinucleated cells and bizarre giant cells. In addition, and undifferentiated carcinoma with a sarcoma-like appearance containing small areas of papillary adenocarcinoma was evident in the tumor.     

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas. A case report

Undifferentiated carcinoma with osteoclast-like giant cells is a rare pancreatic neoplasm, with a possible cystic pattern, includes an adenocarcinoma component and giant cell mimicking osteoclastic bone tumor. We report the case of a 72-year woman admitted for jaundice and epigastric pain. Abdominal ultrasound and computed tomography scan revealed a 6 x 5 cm cystic and solid tumor of the pancreatic head with both bile duct and pancreatic duct dilatation. A pancreaticoduodenectomy was performed and pathologic examination revealed an undifferentiated carcinoma with osteoclast-like giant cells of the pancreatic head. The patient was alive and disease-free with a 18-month follow-up.     

Lobular carcinoma of the breast metastatic to the epidural space: a potential mimic of giant cell bone tumor

We report the case of a 64-year-old woman with a spinal epidural mass. Tissue from a decompression laminectomy disclosed a tumor with numerous osteoclast-like giant cells separated by small, moderately atypical tumor cells. The osteoclast-like giant cells were immunoreactive for vimentin, but negative for epithelial membrane antigen and broad-pectrum cytokeratin. Subsequent breast biopsy revealed a lobular carcinoma of classic type without osteoclast-like giant cells. This is the first reported case in which metastatic breast carcinoma was accompanied by these giant cells but the giant cells were not present at the primary tumor site.     

Surgically resected undifferentiated carcinoma with osteoclast-like giant cells of the periampullary region involving the orifice of the papilla of vater: Report of a case

Undifferentiated carcinomas with osteoclast-like giant cells are rare periampullary neoplasms, which morphologically mimic giant cell tumors of the bone. The terminology, histogenesis, biological behavior, and chemosensitivity of these tumors, and their treatment protocol, remain controversial. We report the case of a 71-year-old man with periampullary carcinoma who underwent pancreaticoduodenectomy under the diagnosis of periampullary carcinoma. Histologically, the neoplasm was composed of undifferentiated cells and evenly spaced osteoclast-like giant cells. Liver and paraaortic lymph node metastases were detected 6 months later and were treated effectively with intravenous gemcitabine. The patient remains in remission 2 years after surgery.     

Papillary Urothelial Bladder Carcinoma Associated with Osteoclast-Like Giant Cells

We report the case of a papillary urothelial carcinoma associated with osteoclast-like giant cells. A 60-year old woman presented with hematuria. A papillary neoplasm was detected by cystoscopy and removed transurethrally. Histological examination revealed a papillary urothelial carcinoma (grade I) associated with multiple stromal giant cells, which displayed morphological, ultrastructural and immunohistochemical characteristics of osteoclast-like giant cells. The formation of osteoclast-like giant cells in association with urothelial bladder carcinoma is a rare event, of which only six cases have been reported in the Anglo-American literature. It may cause diagnostic problems because primary giant cell tumor, giant cell carcinoma and foreign body stromal reaction have to be considered. Immunohistochemistry and electron microscopy may help to rule out these differential diagnoses.     

Pathomorphologic study of undifferentiated carcinoma in seven cases: relationship between tumor and pancreatic duct epithelium

Background/purpose  By the time undifferentiated carcinoma is detected, it has formed a large mass, and it is reportedly difficult to pathologically observe its relationship with the pancreatic duct. In this study, we examined the pancreatic ducts of seven patients of surgical samples, and pathomorphologically investigated the relationship between the adenocarcinomatous and sarcomatous components and the pattern of tumor extension. In addition, we evaluated the usefulness of pancreatic juice cytology by comparison with the findings of the main pancreatic duct (MPD). Methods  Seven primary undifferentiated carcinomas of the pancreas (from three male and four female patients with a mean age of 59 years) were analyzed. Histopathological evaluation was based on the WHO diagnostic criteria. Pancreatic juice cytology was performed and evaluated in two patients. Results  All the undifferentiated carcinomas contained adenocarcinomatous and sarcomatous components, and two had a distinct glandular structure. However, we could not pathomorphologically confirm the continuity of the adenomatous with the sarcomatous components in any of the patients. Three undifferentiated carcinomas contained osteoclast-like giant cells. Pathological observation of the tumor and MPD was possible in three of the seven undifferentiated carcinomas. PanIN-3 was observed in the MPD of three patients, suggesting extension into the MPD. In one of these three, the tumor presented intraductal growth in the MPD, and preoperative pancreatic juice cytology revealed atypical cells with osteoclast-like giant cells. In the remaining two, the tumor extraductally compressed the MPD upward. Conclusions  Undifferentiated carcinoma showed two patterns of cancer extension: (1) invasion and expansive growth during the sarcomatous transformation of adenocarcinoma, and (2) intraductal extension. In addition, some undifferentiated carcinomas showed extension in the MPD. Of note, postoperative pancreatic juice cytology may be useful for the diagnosis.     

Bilateral infiltrating lobular carcinoma of the breast with osteoclast-like giant cells

Abstract: A case of bilateral infiltrating lobular carcinoma of the breast containing osteoclast-like giant cells is presented. Notable pathologic features include prominent tumor-associated angiogenesis and the presence of osteoclast-like giant cells in axillary lymph node metastases. Immunohistologic and ultrastructural examination support a nonepithelial, histiocytic origin for the giant cells, and results are similar to previous reports of osteoclast-like giant cells associated with breast carcinoma. This is the first report of bilateral pure infiltrating lobular carcinoma of the breast with osteoclast-like giant cells and the first case of pure lobular carcinoma with osteoclast-like giant cells present in lymph node metastases.     

Pleomorphic Carcinoma of the Lung with Mediastinal Extension Following Malignant Lymphoma: Report of a Case

In following up a patient with non-Hodgkin's lymphoma, we encountered a case of pulmonary pleomorphic carcinoma with mediastinal direct invasion. A 65-year-old man with hemoptysis was found to have an abnormal shadow in the right upper lung field. A 6.4 × 4.8-cm tumor adjacent to the upper mediastinum occupied the right anterior segment of the upper lobe (S3) and invaded the superior vena cava (SVC). The serum level of neuron-specific enolase was elevated to 11.9 ng/ml. A specimen from a transbronchial lung biopsy of the right B3b bronchus revealed giant tumor cells. A right upper lobectomy with SVC reconstruction was performed. The resected tumor was diagnosed as a pulmonary pleomorphic carcinoma with a large component of giant and spindle cells, and it is considered to be a rare histologic type.     

Undifferentiated carcinoma of the common bile duct: case report and review of the literature

A 78-year-old Japanese man with undifferentiated carcinoma of the common bile duct is presented. Upon gross examination, the common bile duct was found to be obstructed by a nodule measuring 10 x 10 mm. Microscopically, the nodule was ill-defined and composed of atypical spindle-shaped and pleomorphic tumor cells. The spindle-shaped cells proliferated in a whirled or interlacing pattern simulating a sarcoma, and the pleomorphic tumor cells had abundant eosinophilic cytoplasm and bizarre nuclei. Histochemically, a few tumor cells contained mucosubstances stained with the alcian blue (AB) method in their cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for CAM5.2 and AE1/AE3. The histological diagnosis was undifferentiated carcinoma (spindle cell carcinoma) of the common bile duct. Other than our patient, only four other cases of undifferentiated carcinoma in the extrahepatic bile duct have been reported in the literature.     

Pulmonary giant cell carcinoma.

Pulmonary giant cell carcinoma is one of the most highly malignant neoplasms of the lung. Eighteen patients with this tumor are presented. Histologically the neoplasm is composed of a preponderance of multinucleated giant cells, round cells, and spindle cells. Some of the most differentiated tumors show adenocarcinomatous foci and ultrastructural features of secretory epithelium favoring its classification as a variant of pulmonary adenocarcinoma. The giant cells of this neoplasm can be differentiated from those encountered in undifferentiated large cell carcinoma and epidermoid carcinoma by the abundant cytoplasm, the presence of more nuclei and nucleoli, and the significant degree of phagocytosis. The clinical picture and roentgenographic findings present no pathognomonic features.     

Oral undifferentiated high-grade pleomorphic sarcoma: report of a case.

The current World Health Organization classification considers the existence of an undifferentiated unclassifiable category of pleomorphic sarcomas, defined as a group of pleomorphic high-grade sarcomas. Undifferentiated high-grade pleomorphic sarcoma represents about 5% of all soft tissue sarcomas in adults and occurs more commonly in the extremities. In the oral cavity, undifferentiated pleomorphic sarcoma is extremely rare. We report a case of undifferentiated high-grade pleomorphic sarcoma located in the floor of the mouth in a man 56 years old. Microscopically, spindle-shaped cells with accented pleomorphism arranged in a storiform pattern, several bizarre giant cells, and frequent atypical mitoses were observed. The tumor cells were positive only for vimentin, with focal positivity for CD68. The patient was treated by surgery and postoperative radiation therapy, and after 25 months, no recurrence was observed.     

Osteoclastic giant cell tumor of the pancreas

INTRODUCTION

Pancreatic giant cell tumors are rare, with an incidence of less than 1% of all pancreatic tumors. Osteoclastic giant cell tumor (OGCT) of the pancreas is one of the three types of PGCT, which are now classified as undifferentiated carcinoma with osteoclast-like giant cells.

PRESENTATION OF CASE

The patient is a 57 year old woman who presented with a 3 week history of epigastric pain and a palpable abdominal mass. Imaging studies revealed an 18 cm × 15 cm soft tissue mass with cystic components which involved the pancreas, stomach and spleen. Exploratory laparotomy with distal pancreatectomy, partial gastrectomy and splenectomy was performed. Histology revealed undifferentiated pancreatic carcinoma with osteoclast-like giant cells with production of osteoid and glandular elements.

DISCUSSION

OGCT of the pancreas resembles benign-appearing giant cell tumors of bone, and contain osteoclastic-like multinucleated cells and mononuclear cells. OGCTs display a less aggressive course with slow metastasis and lymph node spread compared to pancreatic adenocarcinoma. Due to the rarity of the cancer, there is a lack of prospective studies on treatment options. Surgical en-bloc resection is currently considered first line treatment. The role of adjuvant therapy with radiotherapy or chemotherapy has not been established.

CONCLUSION

Pancreatic giant cell tumors are rare pancreatic neoplasms with unique clinical and pathological characteristics. Osteoclastic giant cell tumors are the most favorable sub-type. Surgical en bloc resection is the first line treatment. Long-term follow-up of patients with these tumors is essential to compile a body of literature to help guide treatment.     

���ƹ�ϸ������ϸ����δ�ֻ����ٰ�5�����������׸�ϰ

??Pancreatic undifferentiated carcinoma with osteoclast-like giant cells: An analysis of 5 cases and literature review TAN Xiao-kai*, LI Le, CHEN Hua, et al. *Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University,Harbin 150001, China
Corresponding author: SUN Bei, E-mail: sunbei70@tom.com
Abstract Objective To investigate the clinicopathological feature, diagnosis and treatment of pancreatic undifferentiated carcinoma with osteoclast-like giant cells (PUC-OGC). Methods The clinical and follow-up data of 5 patients with PUC-OGC who were admitted to the First Affiliated Hospital of Harbin Medical University from October 2014 to December 2017 were analyzed and studied retrospectively. Results As for chief complaint, 4 patients had epigastric pain while one had chill and fever. Four of five patients were normal in CEA and CA19-9 preoperatively and only one was slightly elevated in CA19-9. Four patients underwent distal pancreatectomies with splenectomies and 1 choledochojejunostomy and gastrojejunostomy. Pathological features: Four tumors were located at the body and tail of pancreas while one at the head and neck. The median diameter of the tumor was 4.0 (3.2—10.0) cm. Cystic-solid sections with hemorrhage or necrosis was found in 3 cases and solid section in another one, and no metastasis was seen in the lymph nodes of the whole series. There were a huge number of spindle-shaped mononuclear neoplastic cells and distributed large multinucleated non-neoplastic osteoclast-like giant cells(OGCs) microscopically. One of the 5 PUC-OGC cases was accompanied by mucinous cystadenocarcinoma. Another one received chemotherapy of gemcitabine and S-1 postoperatively. Follow-up to December 2017, 4 patients survived without diseases, 1 had died, and the postoperative survival time was 8 (1—28) months. Conclusion The clinical manifestations of PUC-OGC are not specific, and the diagnosis is mainly based on pathological examination. The optimal treatment may be en-bloc resection and postoperative adjuvant therapy, and the prognosis is inconclusive.     

地诺单抗通过STAT3信号通路抑制骨巨细胞瘤的初步研究

目的 研究STAT3信号通路及其下游相关分子在地诺单抗治疗骨巨细胞瘤过程中的表达变化及其意义。方法 收集我院2013年1月至2018年12月手术治疗的31例骨巨细胞瘤病人,其中28例未经地诺单抗治疗（对照组）,3例经地诺单抗治疗（研究组）。通过苏木素-伊红（hematoxylin and eosin, HE）染色检测骨巨细胞瘤组织经地诺单抗治疗前后的病理学变化;通过免疫组化法检测研究组和对照组的骨巨细胞瘤组织中RANKL、STAT3及其下游分子Bcl-2、Cyclin D1分子的表达差异;通过TUNEL法检测上述两组石蜡切片组织中肿瘤细胞的凋亡情况。结果 HE染色结果：对照组中骨巨细胞瘤组织主要由肿瘤基质细胞和多核破骨样巨细胞组成;研究组中破骨样巨细胞消失,残留部分细长形肿瘤基质细胞,大量网状纤维组织及编织骨形成并替代肿瘤组织;免疫组化检测结果：RANKL主要表达于肿瘤基质细胞;STAT3主要表达于多核破骨细胞胞浆和肿瘤基质细胞胞膜;Bcl-2主要表达于多核破骨样巨细胞胞浆、散在分布于细胞核;Cyclin D1表达于多核破骨样巨细胞的细胞核中。RANKL、STAT3、Bcl-2和Cyclin D1在对照组肿瘤组织中的阳性表达率分别为70%、53%、77%、73%;研究组肿瘤组织中多核破骨样巨细胞消失,残留的肿瘤基质细胞中RANKL表达量明显减少,未见STAT3、Bcl-2、Cyclin D1分子表达;TUNEL法凋亡结果：对照组中仅有少量的肿瘤细胞凋亡,研究组中可见残留的肿瘤细胞明显凋亡。结论 地诺单抗可能通过抑制STAT3 信号通路抑制多核破骨样巨细胞的形成及促进肿瘤基质细胞凋亡。     

Osteoclast-type giant cell neoplasm of salivary gland. A microdissection-based comparative genotyping assay and literature review: extraskeletal "giant cell tumor of bone" or osteoclast-type giant cell "carcinoma"?

Primary salivary gland tumors resembling giant cell tumor of bone are very rare and have unsettled histogenesis. Both mesenchymal and epithelial origins have been suggested. We review 14 cases in the English-language literature and report another case, the first of which to be studied by microdissection-based microsatellite analysis. One-half of the tumors have been associated with a carcinoma, usually salivary duct carcinoma and carcinoma ex pleomorphic adenoma. Significant differences between this tumor and giant cell tumor of bone were observed. Unlike giant cell tumor of bone, in which the nuclei of the mononuclear and giant cells are similar, those of salivary gland show obvious differences between the nuclei of mononuclear cells and osteoclastic giant cells. In addition and in contrast to giant cell tumor of bone, the mononuclear cells of giant cell tumor of salivary gland express epithelial markers (epithelial membrane antigen, EMA; carcinoembryonic antigen, CEA) and androgen receptor. Genotypically, the microsatellite pattern of the giant cell component is more akin to the carcinomatous component and does not resemble giant cell tumor of bone. Biologically, giant cell tumor of salivary gland tends to be more aggressive than giant cell tumor of bone. We conclude that giant cell tumor of salivary gland is an unusual carcinoma that is not related to giant cell tumor of bone.     

Pleomorphic dermal sarcoma: adverse histologic features predict aggressive behavior and allow distinction from atypical fibroxanthoma

The behavior of atypical fibroxanthoma is benign, if strict diagnostic criteria are applied. Tumors with similar pathologic features but deep subcutaneous invasion, necrosis, and/or lymphovascular or perineural invasion are thought to be associated with adverse outcome and are better regarded as pleomorphic dermal sarcoma or undifferentiated pleomorphic sarcoma of skin. This tumor group is not well documented in the literature, and its characteristics are only poorly defined. To study the clinical and pathologic spectrum more comprehensively, we retrieved 32 pleomorphic dermal sarcomas from our departmental files. The tumors were large (median: 25 mm) and exclusively presented on sun-damaged skin with a strong predilection for the head. Typically, elderly men were affected (median age: 81 y). Histologically, these often ulcerated tumors were poorly marginated, asymmetrical, and deeply invasive into deep subcutaneous, muscular, and/or fascial tissues. The tumors were cellular and composed of pleomorphic epithelioid cells, atypical spindle cells, and multinucleated tumor giant cells in varying proportions. Mitotic count was brisk and often atypical. Tumor necrosis was observed in 53%, lymphovascular invasion in 26%, and perineural infiltration in 29%. The majority of tumors showed a predominance of atypical spindle cells in a fascicular arrangement. A sheet-like growth of pleomorphic epithelioid cells or mixed spindle and epithelioid cell features were less frequently observed. Myxoid and keloidal change, a desmoplastic stromal response, pseudoangiomatous and storiform growth patterns, and admixed osteoclast-like giant cells were additional morphologic features in some cases. No immunoreactivity was noted for multiple cytokeratins, S100, HMB-45, desmin, and CD34. Smooth muscle actin was expressed in 70%, CD31 in 48%, epithelial membrane antigen in 16%, Melan A in 6%, and p63 in 1 case. CD10 was expressed in all cases stained. Follow-up (available for 29 patients; median: 24 mo) showed local recurrence in 28% and a metastatic rate of 10%, mainly in the skin. Progressive metastatic disease was observed in 2 patients. Remission was achieved in 1 patient using systemic chemotherapy. The second patient died in the setting of advanced-stage non-Hodgkin lymphoma. No disease-related mortality was noted. Our data underscore the importance of recognizing adverse histologic features in tumors otherwise resembling atypical fibroxanthoma. Deep subcutaneous invasion, tumor necrosis, and perineural and/or lymphovascular invasion confers at least low-grade malignant potential.     

Mixed malignant tumour of the lung.

A mixed malignant tumour of the lung intermediate in type between pulmonary blastoma and carcinosarcoma is described. The epithelial component consisted of squamous carcinoma, undifferentiated carcinoma, and clefts lined by bland epithelial cells. The supporting stroma was composed of pleomorphic sarcoma, fibrosarcoma, chondrosarcoma, osteosarcoma, and indeterminate mesenchymal tissue. The tumour was removed surgically, but the patient died postoperatively with rapidly developing multiple bony and soft tissue metastases. Subcutaneous metastases showed the appearnce of poorly differentiated pleomorphic sarcoma. Published reports of mixed malignant lung tumours are reviewed.     

Giant cell tumor of the extrahepatic biliary tree: a clinicopathologic study of 4 cases and comparison with anaplastic spindle and giant cell carcinoma with osteoclast-like giant cells

We report four previously undescribed primary giant cell tumors of the extrahepatic biliary tree and morphologically compare them with 10 anaplastic spindle and giant cell carcinomas with osteoclast-like giant cells of the gallbladder. Two giant cell tumors were located in the distal common bile duct; one in the cystic duct and one in the gallbladder. The 3 patients with bile duct tumors were male, and the only patient with a gallbladder tumor was a female. The age of the patients ranged from 45 to 60 years with an average of 55 years. The patients with bile duct tumors presented with biliary obstruction, and the patient with a gallbladder tumor presented with symptoms of cholelithiasis and a gallbladder mass. Histologically, the tumors were similar to giant cell tumors of bone. They consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD163 immunoreactivity was restricted to the mononuclear cells, whereas CD68 and HAM 56 labeled only the multinucleated osteoclast-like giant cells. The mononuclear cells were EMA-positive but did not express cytokeratins. Follow-up showed that 3 patients were alive and disease-free 3.7 to 7 years after surgery. The anaplastic spindle and giant cell carcinomas contained a fewer number of osteoclast-like giant cells, and their mononuclear cells showed considerable variation in size and shape, marked cytologic atypia, and numerous mitotic figures. They were focally cytokeratin positive (AE1/AE3; CAM 5.2) and did not label with CD163, CD68, and HAM 56. The benign osteoclast-like giant cells showed immunoreactivity for CD68 and HAM 56 but were negative for CD163 and cytokeratins. Giant cell tumors of the extrahepatic biliary tree are benign true histiocytic neoplasms that should be distinguished from the highly lethal anaplastic spindle and giant cell carcinomas with osteoclast-like giant cells by detailed cytologic analysis and immunohistochemical stains for CD163, CD68, HAM 56, and cytokeratins.     

Pulmonary pleomorphic carcinoma; report of a case

We report a case of a 64-year-old man with pleomorphic carcinoma of the lung and thymic cyst. He was admitted to our hospital because of an abnormal shadow observed on chest X-ray. Computed tomography (CT) showed a mass lesion located in the right upper lobe and a non-invasive anterior mediastinal tumor adjacent to the left brachiocepharic vein. On enhanced CT, the lung mass showed central low-attenuation areas with a substantial enhancement in the periphery. Preoperative transbronchial blushing cytology of the mass revealed adenocarcinoma. With a diagnosis of primary lung cancer (cT3N0M0) and mediastinal tumor, an operation was performed through a median sternotomy. The mediastinal tumor was excised and a right upper lobectomy and were also accomplished, because the lung tumor did not show adhesion or pleural invasion. Histopathologic examination of the resected specimen revealed that the lung tumor composed of a mixture of spindle and giant cell features and contained a component of adenocarcinoma and squamous cell carcinoma. This finding yielded a pathological diagnosis of pleomorphic carcinoma (pT2N0M0). The mediastinal tumor was diagnosed as thymic cyst. The postoperative course was uneventful, and he is currently well 6 months after surgery.