Giant Cell Component Research Articles

Giant cell carcinoma of the urinary bladder

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60–90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50–90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

CENTRAL ODONTOGENIC FIBROMA IN ASSOCIATION WITH BROWN TUMOR OF HYPERPARATHYROIDISM IN A PATIENT WITH NF1 AND RENAL FAILURE

<h3>Objective</h3> Neurofibromatosis type 1 is an autosomal dominant disorder caused by mutations in the NF1 gene at chromosomal location 17q11.2. We present a patient with bone abnormalities and a myriad of lesions secondary to his redeveloping renal failure and NF1. <h3>Clinical Presentation</h3> A 21-year-old male renal transplant recipient with NF1 presented with painless masses and large, irregular radiolucent lesions in the maxilla and mandible. The bone was generally "moth-eaten" with a sparse trabeculation pattern. <h3>Intervention and Diagnosis</h3> Histologic examination of an incisional biopsy of the left mandibular lesion revealed two types of tissue with distinct histologic features. Approximately 3/4ths of the specimen was made up of variably cellular dense fibrous connective tissue interspersed with numerous inactive islands and cords of odontogenic epithelium. The remaining specimen consisted of abundant multinucleated giant cells embedded within a highly cellular stroma containing extravasated erythrocytes and hemosiderin. Throughout the specimen, seams of lace-like osteoid and irregular trabeculae of woven bone were noted. The lesion was diagnosed as a central odontogenic fibroma (COdF) in association with a central giant cell lesion, most consistent with brown tumor of hyperparathyroidism. The bone changes were interpreted to be highly suggestive of renal osteodystrophy. <h3>Conclusion</h3> Around 30 cases of hybrid central giant cell granuloma-like lesion in association with central odontogenic fibroma have been reported. This, to the best of our knowledge, is the first reported case of brown tumor in association with COdF. It has been proposed that a primary COdF induces a reactive giant cell response, however, this is unlikely here, given that the primary tumor was probably a ‘brown tumor'. Our case illustrates the point that the giant cell component may be the initiating entity in these hybrid lesions.

Response to neoadjuvant chemotherapy in histologic variants of bladder cancer.

458 Background: Localized muscle invasive bladder carcinoma is mostly treated with neoadjuvant chemotherapy (NAC) before surgery in order to improve the outcome. Urothelial carcinoma (UC) is the most frequent histological type. Histological variants (pure or mixed) occur in 10% of bladder carcinoma. There is a lack of data on NAC efficacy for these histological subtypes. In this study, we evaluated the histologic response to NAC in the variant population of bladder cancer. Methods: Patients from 2 french hospitals (CHU de Nantes and ICM) treated with NAC for bladder cancer from 2010 to August 2021 were included in this retrospective study. We compared response to NAC between UC and histologic variants (pure or mixed) on cystectomy piece. The histological response was defined by the tumor downstaging after NAC (≤pT1Nx). We also collected the pathological complete response (pCR), which was defined by no residual tumor on the cystectomy piece. Results: 87 patients were included. 31 patients harbored a variant pattern: 7 squamous component, 3 adenocarcinoma component, 5 micropapillary component, 2 sarcomatoid component, 4 neuroendocrine carcinoma, 4 nest, 1 lymphoepithelial carcinoma, 2 giant cell, 1 undifferentiated, 1 micropapilallary and adenocarcinoma component and 1 adenosquamous component; 56 were conventional UC. NAC was MVAC in 77% of patient in the variant group, and 82% in the UC group. Others chemotherapy drugs were used as gemzar cisplatine, and platine etoposide. Downstaging was observed in 55% of patients in the variant group (17/31) and in 59% in the UC group (33/56). The difference was not statistically significant (p &lt;0,44). pCR was observed in 39% of patients in the variant group (12/31) and 43% in the UC group (24/56), the difference was not significant (p&lt; 0.44). Conclusions: NAC can be effective in the histologic variant population of bladder carcinoma, nevertheless these data could be confirmed in a larger cohort.

Benign albeit glycolytic: MCT4 expression and lactate release in giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a histologically benign, locally aggressive skeletal lesion with an unpredictable propensity to relapse after surgery and a rare metastatic potential. The microscopic picture of GCTB shows different cell types, including multinucleated giant cells, mononuclear cells of the macrophage-monocyte lineage, and spindle cells. The histogenesis of GCTB is still debated, and morphologic, radiographic or molecular features are not predictive of the clinical course. Characterization of the unexplored cell metabolism of GCTB offers significant clues for the understanding of this elusive pathologic entity. In this study we aimed to characterize GCTB energetic metabolism, with a particular focus on lactate release and the expression of monocarboxylate transporters, to lie down a novel path for understanding the pathophysiology of this tumour. We measured the expression of glycolytic markers (GAPDH, PKM2, MCT4, GLUT1, HK1, LDHA, lactate release) in 25 tissue samples of GCTB by immunostaining and by mRNA and ELISA analyses. We also evaluated MCT1 and MCT4 expression and oxidative markers (JC1 staining and Bec index) in tumour-derived spindle cell cultures and CD14+ monocytic cells. Finally, we quantified the intratumoural and circulating levels of lactate in a series of 17 subjects with GCTB. In sharp contrast to the benign histological features of GCTB, we found a high expression of glycolytic markers, with particular reference to MCT4. Unexpectedly, this was mainly confined to the giant cell, not proliferating cell component. Accordingly, GCTB patients showed higher levels of blood lactate as compared to healthy subjects. In conclusion, taken together, our data indicate that GCTB is characterized by a highly glycolytic metabolism of its giant cell component, opening new perspectives on the pathogenesis, the natural history, and the treatment of this lesion.

TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors.

BackgroundGiant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than “classic” IDHwt GBM.MethodsWe studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data.Resultsp53 was altered by gene mutation or protein overexpression in all cases, while driver IDH1, IDH2, BRAF, or H3F3A mutations were infrequent or absent. Compared to IDHwt GBMs, gcGBMs had a significant higher frequency of TP53, ATRX, RB1, and NF1 mutations, while lower frequency of EGFR amplification, CDKN2A deletion, and TERT promoter mutation. Almost all tumors had low TML values. The high TML observed in only 2 tumors was consistent with POLE and MSH2 mutations. In the histopathological review of TCGA IDHwt, TP53-mutant tumors identified giant cells in 37% of the cases. Considering our series and that of the TCGA, patients with TP53-mutant gcGBMs had better overall survival than those with TP53wt GBMs (log-rank test, P < .002).ConclusionsgcGBMs have molecular features that contrast to “classic” IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine.

Clinical case of mandibular fibro-osseous lesions with giant multinuclear cells: molecular-genetic differential diagnostic analysis

The giant cell tumors of maxillofacial bones include several barely differentiable diseases with diverse prognoses. A case of a giant cell tumor in an 18-year-old man is described. Clinical, instrumental and laboratory examination did not allow to establish an accurate diagnosis. Molecular genetic test by New generation sequencing (NGS) of tumor tissues and blood identified mutation p. 1424 C&gt; A; p.Pro475His in the SH3BP2 gene, previously described in patients with the so-called cherubism, that determined the tactic of treatment. Carrying out an oncogenetic study allows the differential diagnosis of such morphologically similar conditions with a giant cell component as a multiorgan form of fibrous dysplasia, reparative granulomas, Noonan syndrome, Sturge-Weber-Crabbe syndrome, juvenile ossifying fibroma.

The diagnostic utility of zinc E-box 1 (ZEB1) transcription factor for identification of pulmonary sarcomatoid carcinoma in cytologic and surgical specimens

Although uncommon, pulmonary sarcomatoid carcinoma carries a worse prognosis due to poor chemotherapeutic response. Currently, a histologic spindle and/or giant cell component indicates sarcomatoid differentiation, with zinc E-box binding homeobox 1 (ZEB1) implicated in promoting epithelial-mesenchymal transition. However, diagnostic use of ZEB1 in limited specimens, including cell block (CB) preparations, remains unclear. Pulmonary sarcomatoid (SARC, n = 15), typical (TC, n = 10) and atypical carcinoid (AC, n = 10), small cell (SCLC, n = 8) and large cell neuroendocrine carcinoma (LCNEC, n = 9), squamous cell carcinoma (SQ, n = 7), and adenocarcinoma (ADC, n = 7) CBs along with 69 SARCs, 20 TCs, 21 ACs, 9 SCLCs, 10 LCNECs, 71 SQs, 402 ADCs, 16 large cell carcinoma (LCC) and 17 other thoracic tumor (OT) surgical specimens between 2007 and 2018 were retrieved. ZEB1 (Sigma Aldrich, St. Louis, Mo and Novus Biological, Centennial, Colo) immunohistochemistry was graded 1+ to 3+, with ≥1+ and >5% staining considered positive. Nuclear ZEB1 was seen in 80% SARC (12/15), 0% TC (0/10), 0% AC (0/10), 12.5% SCLC (1/8) and 11.1% LCNEC (1/9), 0% SQ (0/7), and 0% ADC (0/7) CBs. In surgical specimens, 75.4% SARCs (52/69), 0% TCs (0/20), 0% ACs (0/21), 11.1% SCLCs (1/9), 30% LCNECs (3/10), 0% SQs (0/71), 0.2% ADCs (1/402), 12.5% LCCs (2/16), and 11.8% OTs (2/17) demonstrated ZEB1. ZEB1 sensitivity and specificity in cytology and surgical specimens were 80% and 96.1%, and 75.4% and 98.1%, respectively. ZEB1 is sensitive and highly specific for pulmonary sarcomatoid carcinoma in limited cytologic and surgical specimens. Diagnostic pitfalls include high-grade neuroendocrine tumors and large cell carcinoma, which are resolvable by morphologic considerations.

Osteoclast-like giant cell–rich carcinomas of the lung: a clinicopathological, immunohistochemical, and molecular study of 3 cases

Three cases of primary carcinomas of the lung each with an extensive osteoclast-like giant cell component are presented. The patients are 3 men between the ages of 58 and 67 years (average, 62.5 years) who presented with nonspecific symptoms. A history of malignancy, infectious, or granulomatous disease was negative in all the patients. Diagnostic imaging disclosed the presence of a large intrapulmonary mass; in 1 case in the right upper lobe and in 2 cases in the right lower lobe. Surgical resection via lobectomy was performed in the 3 patients. Grossly, the tumors were described as soft, friable intrapulmonary masses, reddish in color, and measuring from 6 to 13 cm in largest diameter. Histologically, the tumors were each characterized by the extensive presence of a multinucleated osteoclast-like giant cell component, which represented approximately 80% of the tumor mass. The osteoclast-like giant cell component was admixed with a sarcomatoid carcinoma in 2 cases and an adenocarcinoma in 1 case. Immunohistochemistry showed that the osteoclast-like giant cells were positive for CD-68, cathepsin K, and histone H3, whereas the carcinoma component was positive for keratin, thyroid transcription factor-1, and histone H3 (patchy). Molecular studies were performed in 2 patients with negative results. Clinical follow-up was obtained in 2 patients; 1 died 14 months after initial diagnosis, whereas 1 remains alive 6 months after initial diagnosis. One patient was lost to follow-up. The current neoplasms represent an unusual type of lung carcinoma that needs highlighting as a separate type from conventional giant cell carcinoma.

Efficacy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in patients with advanced pulmonary pleomorphic carcinoma

ObjectivesPulmonary pleomorphic carcinoma (PC) is a rare type of lung tumor with a dismal prognosis. There is no consensus on a chemotherapy regimen for PC, and conventional platinum-based chemotherapy has been associated with disappointing response rates and PFS. In searches for a new regimen, the sarcomatoid (spindle or giant cell) component has been assumed to be susceptible to chemotherapy used for soft tissue sarcoma. Materials and methodsThe medical records of 17 patients who received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for advanced PC between January 2010 and February 2017 were retrospectively analyzed for clinicopathological features and outcomes. Results and conclusionThe median age was 59 years. Sixteen patients were male, and only one patient had never smoked. Six patients achieved partial response to MAID, leading to an objective response rate of 35%. The median PFS was 2.8 months, and the median OS was 8.7 months. Hematologic toxicity-related adverse events were the most frequent, which comprised grade 3–4 anemia in 35% of patients, neutropenia in 47%, thrombocytopenia in 24%, and febrile neutropenia in 29%. No febrile neutropenia was reported in patients who received 5-day granulocyte-colony stimulating factor (G-CSF) prophylaxis. Most adverse events resolved without complications, except for one death due to sepsis.MAID is an effective, and possibly important, regimen for PC. MAID could be more safely used in clinical practice with appropriate dose modifications and G-CSF primary prophylaxis according to patients’ status.

Pulmonary sarcomatoid carcinoma: an analysis of a rare cancer from the Surveillance, Epidemiology, and End Results database.

Pulmonary sarcomatoid carcinoma (PSC) is a rare malignant neoplasm that accounts for a small percentage of non-small-cell lung carcinoma (NSCLC). At least 10% of PSCs has a spindle and/or giant cell component, which is often associated with a poor prognosis. We reviewed the Surveillance, Epidemiology, and End Results (SEER) database for the clinicopathological characteristics and surgical outcomes of PSCs. The SEER database (1973-2013) was queried for PSC. A comparison between PSC and other NSCLC patients was performed. Cox regression for overall survival (OS) and logistic regression for node-positive predictors were performed. A propensity-matched (1:2) analysis (including age, gender, grade and stage) among surgically treated cases was done to compare OS in PSC versus other NSCLCs. A total of 955 899 NSCLC patients were identified; of these, 4987 patients had been diagnosed with PSC (0.52%). Men represented 60.9% of cases, with a median age of 68 years. The median size of the tumour was 5 cm and 3.5 cm in PSCs and NSCLCs, respectively (P < 0.001). PSC patients had significantly less Stage I, more high-grade tumours, advanced T stage, N+ disease and M1 disease (P < 0.001). In the PSC cohort, the most significant predictor of N+ disease on multivariate analysis was advanced T stage (P < 0.001). Predictors of OS in Stages I/II PSC on multivariate analysis were advanced age [P < 0.001, hazard ratio (HR) = 1.03], male gender (P = 0.024, HR = 1.25), carcinosarcoma (P = 0.002, HR = 1.76), grade (P = 0.033, HR = 1.81), T stage (P = 0.003, HR = 1.75), N status (P = 0.001, HR = 1.90) and surgical resection (P < 0.001, HR = 0.58). Among matched surgically resected cohorts, a poorer prognosis for OS was evident in PSCs in early stages (I/II) than in other NSCLCs (P = 0.009). PSC patients present with more advanced stage and with worse survival outcomes than other NSCLC patients. While surgical resection conveys a survival advantage in PSC, this group represents a population at a high risk for relapse and should be evaluated for novel adjuvant therapies.

PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis.

Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis. Thirty-six patients who underwent surgical resection of a PSGSCC were included. PD-L1 (E1L3N) expression on tumor cells and PD1 (NAT105) expression by tumor infiltrating lymphocytes (TILs) were performed by immunohistochemistry. Results were compared to immunohistochemistry tests of TTF1, Napsin A, p40 and to molecular study of EGFR, KRAS, BRAF and HER2. Seventy-five % of PSCGCC were considered as positive for PD-L1.PD-L1 expression in PSGSCC is associated with TTF-1 and/or Napsin A expression (47.2%, p = 0.039). Few p40 positive PSCGCC expressed PD-L1 (8.3%, p = 0.013). PD1 expression was not related to TTF-1 and/or Napsin A expression (p = 0.47), p40 expression (p = 0.68) or survival (p = 0.14). PD-L1 or PD1 expression were not related to the age, gender, pT, pN, stage, visceral pleura invasion, histopathological subtype, the presence of giant cell component, the predominance of sarcomatoid component, and the presence of EGFR or BRAF or HER2 or PIK3CA mutation (p>0.05). PD-L1 expression was correlated with a worse overall survival in PSCGCC (p = 0.045). PD-L1 expression is frequent in PSCGCC and might be associated with the expression of adenocarcinoma markers (TTF-1, Napsin A) or the lack of expression of squamous cell carcinoma marker (p40).

Combined small cell lung carcinoma and giant cell carcinoma: a case report

BackgroundCombined small cell lung carcinoma (SCLC) is defined as SCLC combined with elements of non-small cell lung carcinoma (NSCLC), accounting for approximately 30% of cases of SCLC. However, combined SCLC and giant cell carcinoma (GC) is very rare.Case presentationA 50-year-old woman with a 45 pack-year smoking history was referred to our hospital for further investigation of an abnormal left hilar shadow. Chest computed tomography (CT) revealed a 28-mm solid pulmonary nodule in the left lower lobe and an enlarged left hilar lymph node adjacent to the left main pulmonary artery. CT-guided biopsy of the pulmonary nodule led to the diagnosis of high-grade neuroendocrine carcinoma. The preoperative clinical stage was defined as cT1bN1M0. Thus, the patient underwent left lower lobectomy with ND2a-2 lymph node dissection via thoracotomy. Pathological investigation revealed a 22-mm tumor and dense sheet-like growth of small tumor cells with scant cytoplasm and finely granular nuclear chromatin. Moreover, there was a sheet-like growth of bizarre, highly pleomorphic mono- or occasionally multinucleated giant cells, accounting for approximately 40% of the tumor. Both the small and giant cell components were thyroid transcription factor-1-positive and p40-negative and exhibited neuroendocrine differentiation, as indicated by positivity for synaptophysin and CD56 and negativity for chromogranin A. While the small cell component was E-cadherin-positive and vimentin-negative, the giant cell component was E-cadherin-negative and vimentin-positive, indicating an epithelial-to-mesenchymal transition. Only the small cell component was found within the mediastinal and hilar lymph nodes. The final pathological diagnosis was combined SCLC and GC, pT1bN2M0, and pStage IIIA. The patient received adjuvant chemotherapy with 4 cycles of cisplatin and irinotecan. No sign of recurrence has been noted for 1 year after the surgery.ConclusionsThis is the first detailed report of a unique case with combined SCLC and GC. The coexistence of SCLC and GC in the presented case might indicate several possibilities: (1) GC may arise from SCLC via epithelial-to-mesenchymal transition, (2) SCLC may arise from GC through phenotypic conversion, and (3) SCLC and GC may have derived from a common neuroendocrine origin. Further investigation is necessary to reveal the underlying pathological process.

Pleomorphic giant cell carcinoma of the urinary bladder

Pleomorphic giant cell carcinoma is a rare aggressive variant of urothelial carcinoma characterized by the presence of highly pleomorphic bizarre tumor giant cells similar to giant cell carcinoma of the lung. Although mentioned in the 2004 WHO classification as a type of urothelial carcinoma with giant cells, characteristics of pleomorphic giant cell carcinoma were described in the literature only in 2009 when Lopez Beltran et al . reported a series of 8 cases. It occurs more commonly in older males (ages ranging 55–88 years) with patients presenting with hematuria, dysuria or frequency. The pleomorphic giant cell component in the reported series varied from 20% to 100% of the tumor. This tumour has expansile masses of pleomorphic epithelioid tumor with bizarre anaplastic multinucleated and mononu-cleated tumor giant cells. Extensive necrosis is common. Tumor cells have abundant cytoplasm, and have frequent typical or atypical mitotic figures. Tumour cells are positive for CK7, CAM 5.2, AE1/AE3 and EMA. Some cases are positive for P63, thrombomodulin and Uroplakin111. This tumour must be differentiated from metastatic malignancy to the bladder including pleomorphic giant cell carcinoma of the prostate. This tumor has a very poor prognosis. Patients often have advanced stage cancer at presentation.

Tumor-Induced Osteomalacia: Increased Level of FGF-23 in a Patient with a Phosphaturic Mesenchymal Tumor at the Tibia Expressing Periostin.

In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. Electron microscopy demonstrated a poorly differentiated mesenchymal tumor with a multifocal giant cell component and evidence of neurosecretory-granules. However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. The patient is still in complete remission after 34 months. Tumor resection of PMTMCTs is the therapy of choice. Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. The prognostic value of expression of Periostin has to be evaluated more precisely in a larger series of patients with TIO.

Clear cell renal cell carcinoma with a syncytial-type multinucleated giant tumor cell component: implications for differential diagnosis

A component of syncytial-type multinucleated tumor giant cells is uncommon in clear cell renal cell carcinoma, and the histogenesis, incidence, and clinical implications of this finding are not well understood. We retrieved 13 such tumors from our pathology archives in patients with a median age of 60years, comprising 1.5% of clear cell renal cell carcinomas. Stage was typically pT4 or pT3 (each 38%). Microscopically, all tumors included a component of low-grade clear cell renal cell carcinoma with usual features. Syncytial-type giant tumor cells possessed voluminous cytoplasm, usually granular and eosinophilic, and numerous nuclei similar to those of the mononuclear tumor cells. Transition between areas of mononuclear and multinucleated cells was sometimes abrupt. Other findings included necrosis (77%), hyaline globules (46%), emperipolesis (46%), and intranuclear cytoplasmic invaginations (23%). Immunohistochemical staining typically revealed both mononuclear and multinucleated cells to be positive for carbonic anhydrase IX, CD10, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3 and negative for β human chorionic gonadotropin, TFE3, cathepsin K, cytokeratin 7, cytokeratin 20, HMB45, CD68, smooth muscle actin, and S100. Most patients with available information (7/9) were alive with metastatic disease at the most recent follow-up. Syncytial-type giant cells are an uncommon finding associated with aggressive clear cell renal cell carcinomas. Despite the unusual appearance of this tumor component, its immunoprofile supports an epithelial lineage and argues against trophoblastic, osteoclast-like, or histiocytic differentiation. Reactivity for typical clear cell renal cell carcinoma antigens facilitates discrimination from giant cells of epithelioid angiomyolipoma or other tumors, particularly in a biopsy specimen or a metastatic tumor.

Benign Looking Giant Cell Component in Dedifferentiated Chondrosarcoma

Dedifferentiated chondrosarcomas (DDCS) account for approximately 10% of all chondrosarcoma cases and its 5-year survival is only 10%. The dedifferentiated components of DDCS could be osteosarcoma, malignant fibrous histiocytoma, and fibrosarcoma. In this article, the authors report a rare case of DDCS in a 19-year-old female, in which the dedifferentiated component showed a close histological resemblance to a giant cell tumor of bone. Radiological diagnosis revealed an expansive osteolytic lesion in the epiphysis of right proximal humerus, which also extended to the diaphysis with irregular calcification and focal cortical breakthrough. The biopsy tissue contained the features of a giant cell tumor of bone and well-differentiated cartilage. Pathological examination revealed a biphasic tumor comprising of low-grade chondrosarcoma and nonchondroid giant cell-rich lesion similar to conventional giant cell tumor of bone, and there is an abrupt transition between the 2 components.

Giant cell ependymoma of the thoracic spinal cord

We report a new case of giant cell ependymoma (GCE) of the thoracic spinal cord. Ependymomas predominate in children and young adults and are frequently intracranial and infra-tentorial. However, a second age peak at 30-40 years is reported for spinal tumours. Microscopically, ependymomas show a large variety of histological features, among which a rare variant with giant cells. This 59-year-old woman presented with a 6-month history of numbness and burning sensation affecting the left lower limb and hemi-trunk. A cervico-thoracic MRI revealed a solid intra-medullary tumour at the level of T1-T3, slightly T1-hypointense, T2-hyperintense and contrast enhancing. A complete surgical resection was carried out through a C7 to T4 laminectomy. Recovery was complete with no sign of recurrence at 18-month follow-up. The initial histological diagnosis of glioblastoma was challenged on the basis of the imaging and operative findings of a well-circumscribed tumour. The case was sent to us for second opinion and we diagnosed a GCE, WHO grade II, with a biphasic pattern including a predominant giant cell component (>90%), with genetic evidence of polyploidy, and a very limited classic component, showing a characteristic loss of chromosome 22. Our report adds to the clinical, imaging, pathological and genetic characterisation of GCE and brings the first genetic evidence that these rare tumours are at least bi-clonal. It also suggests that GCE have a good prognosis after complete surgical resection.

Pulmonary Carcinoma with β-Human Chorionic Gonadotropin Expression: Further Understanding and Suggestions for This Entity from Six Cases Experience in a Single Institution

Purpose: β-human chorionic gonadotropin (β-hCG) expressing pulmonary carcinoma is very rare, and little is known about this entity. The aim of this study was to find the characteristic clinicopathologic features of β-hCG expressing pulmonary carcinoma. Materials and Methods: Of all 2790 lobectomy specimens of lung excised between January 2006 and December 2010, only six cases of β-hCG expressing pulmonary carcinoma were identified retrospectively. The cases were classified according to the WHO classification, and clinicopathologic features were investigated. Results: The patients consisted of 4 males and 2 females, and the median age was 64 years. Half of the patients presented with blood tinged sputum or hemoptysis. The median tumor diameter was 4.2 cm. All but one case showed prominent area of hemorrhage and necrosis. All six cases were pleomorphic carcinoma, composed of various types of non-small cell carcinomatous component and giant cell component. All cases showed significant area of β-hCG positivity, and β-hCG was usually expressed in the pleomorphic giant cells. Conclusion: In pulmonary carcinoma with pleomorphic giant cells, is necessary to check

Endometrial Giant Cell Carcinoma: A Case Series and Review of the Spectrum of Endometrial Neoplasms Containing Giant Cells

Poorly differentiated endometrial carcinomas of specific type include the rarely reported endometrial carcinoma with a malignant giant cell component [endometrial giant cell carcinoma (GCC)]. Since the initial description in 1991, there has only been 1 subsequent case report of this entity. We report another 5 cases. The patients ranged in age from 53 to 83 years, presenting with vaginal bleeding, anemia, or a pelvic mass. Four of the 5 tumors contained areas of endometrial adenocarcinoma of usual type, with a variable giant cell component. The conventional cell types present included 1 case with clear cell carcinoma (30% of tumor volume), 2 with high-grade endometrioid carcinoma (50% and 70% of tumor volume, respectively) and 1 with serous histology (10% of tumor volume). One was composed exclusively of giant cell carcinoma. The giant cell component in all cases consisted of poorly cohesive nests of bizarre multinucleated giant cells with mononuclear tumor cells. A striking peritumoral and intratumoral inflammatory cell infiltrate composed of lymphocytes, plasma cells and focal eosinophils, and neutrophils was present and emperipolesis was noted in 4 of the 5 cases. The giant cells showed focal staining for epithelial markers (AE1/AE3 and CAM 5.2). Three of the patients presented with stage 1A disease, 1 with stage 1B disease, and 1 tumor was advanced, presenting as stage IIIC2. One patient in whom the tumor was exclusively of the giant cell type, developed lung metastasis 4 years after diagnosis and 1 patient is disease free after 14 years. The remaining 3 patients showed no evidence of disease with 15 to 32 months of follow-up. As histotype supplemented by staging information is critical in selection of treatment modalities and in prognostication in uterine malignancies, accurate classification is mandated. Here, we present a series of endometrial carcinomas containing a component of GCC and discuss the spectrum of giant cell-containing uterine neoplasms. At this time, however, the cumulative data on endometrial GCC are limited and the prognostic significance of the presence and the extent of a giant cell component in endometrial carcinoma remains uncertain.

A method for the treatment of supergranulation advection by giant cells

Aims. We present a new method for the treatment of the advection of solar supergranulation by giant cells, a large-scale analogue to the observed property of granule advection by supergranules. Methods. The proposed method is derived from a description of solar convection via spherical harmonics and spectral coefficients, allowing the investigation of the influence of a giant cell component on a realistic supergranule signal. Results. We show that a supergranule pattern derived from real data, as well as a simplified test signal, can be advected by a giant cell component of various sizes. Conclusions. The identified behaviour is in analogy to observed supergranulation patterns, including those based on MDI Dopplergrams, which show wavelike supergranulation patterns, even after the removal of the geometric projection effect. Our method is an important step towards the construction of future models involving supergranule flow patterns advected by a giant cell flow. Nevertheless, additional efforts are required to obtain a final verification of giant cells as a separate component of the solar photospheric convection spectrum.