Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Primary giant cell carcinomas of the lung: a clinicopathological and immunohistochemical analysis of seven cases.

AIMS: Seven cases of primary giant cell carcinomas of the lung are presented. METHODS AND RESULTS: The patients were five women and two men between the ages of 48 and 72 years (average: 63 years). Clinically, the patients presented with symptoms of cough, chest pain, dyspnoea and general malaise. Diagnostic imaging revealed the presence of intrapulmonary masses; five tumours were located in the right lung and two in the left, with a general predilection for the upper lobes. All patients underwent surgical resection and staging of their tumours. Five patients were staged as T2 and T3 with nodal metastasis, while two patients in stages T1 and T3, respectively, had no nodal disease. Histologically, the giant cells were typed as syncytiotrophoblast-like or 'null type', according to the expression of ß-human chorionic gonadotrophin or expression of cytokeratin alone. Follow-up information revealed that five patients died within a period of 1-3 years, while two patients remain alive between 1 and 3 years. CONCLUSIONS: The cases presented herein highlight the importance of separating these tumours from the group of sarcomatoid carcinomas and analysing them carefully by immumohistochemical means, as we believe that these neoplasms represent a specific tumour entity.

Small bowel intussusception caused by multiple intestinal metastases from a giant cell carcinoma of the lung: a case report.

Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature.

[Case of giant cell anaplastic ductal carcinoma of the pancreas].

A 56-year-old woman was admitted to our hospital with fever and systemic malaise. Abdominal computed tomography revealed an enhanced tumor of the pancreatic head, measuring 9cm in maximal diameter and containing a low-density area. Subtotal stomach-preserving pancreatoduodenectomy was performed. Hemorrhage and necrosis were evident within the tumor, and osteoclastic polynuclear giant cells were also identified. A diagnosis of giant cell anaplastic ductal carcinoma of the pancreas was made. The patient has been free from recurrence for 6 months since surgery.

Giant cell carcinoma of the urinary bladder : Clinicopathologic analysis and oncological outcomes.

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.

Osteoclast-Like Giant Cell Tumors of the Pancreas: Clinical Characteristics, Genetic Testing, and Treatment Modalities.

OBJECTIVES: This study sought to better characterize patient characteristics, treatment options, and outcomes for osteoclast-like giant cell carcinoma of the pancreas, a rare subtype of pancreatic adenocarcinoma. METHODS: This is a retrospective study of all patients with osteoclast-like giant cell carcinoma of pancreatic origin treated at Mayo Clinic from 2000 to present. Baseline patient characteristics, treatment modalities utilized, and outcomes were compiled. Overall survival (OS) and progression-free survival were assessed using Kaplan-Meier analysis with a significance level of P ≤ 0.05. RESULTS: Fifteen patients met criteria for inclusion. Four patients had distant metastases at diagnosis, the remaining 11 with locoregional disease. Median OS for the entire cohort was 11 months. Metastatic disease was associated with significantly shorter OS (3.5 vs 14.1 months; P = 0.005). Three patients had no evidence of disease at time of analysis; all 3 were treated with complete resection followed by adjuvant chemotherapy. CONCLUSIONS: Osteoclast-like giant cell carcinoma of the pancreas is an aggressive malignancy with poor prognosis. For patients with locoregional disease, surgical resection followed by adjuvant chemoradiation may play a role in extended disease-free survival. Metastatic disease presents a challenging entity to treat with little data to support any effective chemotherapy regimens.

Gestational pulmonary giant cell carcinoma - An autopsy report.

Cancer is an uncommon event in pregnancy. The most common gestational cancers arise from the breast and cervix. Although lung cancer is the most common malignancy, its occurrence in pregnancy is a distinctly rare event. Diagnosing it during pregnancy is an additional challenge as the pregnancy, common respiratory ailments, and the lung cancer can have overlapping symptoms. We report an uncommon histological variant of lung cancer - giant cell carcinoma, which resulted in a fatal outcome in a 26-year-old pregnant woman. A high level of suspicion and vigilance should be exercised during pregnancy to diagnose such rarer entities.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Giant cell lung carcinoma in a man with acquired immunodeficiency syndrome.

A 66-year-old man, who was discovered to have human immunodeficiency virus (HIV) infection 22 months previously and was treated with highly active antiretroviral (HAART) therapy, developed giant cell carcinoma of the lung. In English literature, this is the first case of such cell type of lung cancer during HAART therapy. Since giant cell carcinoma of the lung occurs mainly in elderly men who smoke heavily, there may not be a possibility that the HIV or HAART was causative in our patient.

Giant cell tumour of the triquetrum.

We present details of a case of giant cell tumour of bone (GCTOB) involving the triquetrum. GCTOB arising within the carpus is exceedingly rare and, to our knowledge, this is only the second case of monostotic GCTOB of the triquetrum that has been reported.

[Maldiagnosis of giant-cell tumor of the bone in a patient with hyperparathyroid osteodystrophy].

The paper describes a case of maldiagnosis of giant-cell tumor in a patient with parathyroid osteodystrophy, in this connection elbow joint resection and replacement were made. Parathyroid adenoma with the symptoms of primary hyperparathyroidism was diagnosed only two years after surgery. Progression of diseases was accompanied by severe bone changes and the development of urolithiasis complicated by chronic renal failure. Thus, the interpretation of bone tissue changes without considering clinical and laboratory data led to the unwarranted surgical intervention and the late diagnosis of primary hyperparathyroidism. Differential diagnosis of a giant-cell tumor should be made, by obligatorily considering clinical and laboratory data, including the parameters of calcium metabolism.

Osteoclast-like Giant Cell-type Pancreatic Anaplastic Carcinoma Presenting with a Duodenal Polypoid Lesion.

Osteoclast-like giant cell-type (OCGC) anaplastic carcinoma is a rare variant of pancreatic ductal adenocarcinoma, and its imaging characteristics and progression pattern have not been fully clarified. The patient was a 73-year-old man who had been incidentally found to have a pancreatic head tumor. Computed tomography demonstrated a 3-cm marginally enhanced mass at the pancreatic head, continuing toward the duodenum. Diffusion-weighted magnetic resonance imaging showed a retained diffusion capacity. Duodenoscopy revealed a 1.5-cm polypoid lesion, covered by a dirty coat, near the major papilla. Surgical material revealed OCGC pancreatic anaplastic carcinoma protruding to the duodenum, accompanied by multiple hemorrhagic foci and hemosiderin precipitations.

Giant cell carcinoma of the lung presenting as an isolated cyst containing air: A case report.

INTRODUCTION: Pulmonary sarcomatoid carcinomas (PSCs) are rare tumors within the sarcomatoid carcinoma group. Giant cell carcinoma of the lung (GCCL) is a rare type of PSCs that consists entirely of highly pleomorphic tumor giant cells; the prognosis is poor. PATIENT CONCERNS: A patient presented with a single cyst and was diagnosed with GCCL. The patient was a 59-year-old male who was admitted to the hospital with a cough. A chest computerized tomography (CT) scan showed a single, thin-walled cyst containing air in the left upper lobe of the lung. Bronchoscopy revealed chronic bronchitis. The initial diagnosis was pulmonary infection and the patient was treated with antibiotics. The cyst wall increased in thickness, and the cyst eventually formed a cavity. DIAGNOSIS: Surgery was performed, and a diagnosis of GCCL was established. The stage was pT1bN1M0 (equal to stage IIB). INTERVENTIONS: The patient underwent video-assisted thoracoscopic surgery and 4 cycles of adjuvant chemotherapy consisting of cisplatin and docetaxel. After 9 months, the patient occurred mediastinal lymph node metastasis, and received radiotherapy (60Gy/30F). OUTCOMES: His prognosis was good without progression (complete response) based on serial CT scans over 9 months of follow-up evaluations, then the patient occurred mediastinal lymph node metastasis. The patient lived during 30 months of follow-up, after which he was lost to follow-up. CONCLUSION: A solitary pulmonary parenchymal cystic lesion usually suggests an infectious disease or congenital abnormality; however, a cystic lesion is occasionally encountered in GCCL.

In vivo proton spectroscopy of giant cell tumor of the bone.

OBJECTIVE: The proton MR spectroscopic finding of elevated choline has been reported to be useful in the differentiation of malignant from benign musculoskeletal tumors. This study was designed to evaluate the MR spectroscopy features of giant cell tumor (GCT) of the bone, primarily to determine whether the presence of choline is a frequent occurrence in these tumors and whether MR spectroscopy features can be correlated with clinical, radiologic, and histopathologic findings. SUBJECTS AND METHODS: MRI, dynamic contrast-enhanced MRI, and proton MR spectroscopy were performed in 33 patients with bone tumors on a 1.5-T MR scanner. Of these, 12 patients who had GCT of the bone form the subject material for this study. Dynamic contrast-enhanced MRI and single-voxel proton MR spectroscopy were performed after preliminary evaluation with radiography. Patients were divided into two groups, those with elevated choline levels and those without a choline peak on MR spectroscopy. The clinical and radiologic features, including the Campanacci stage and dynamic MRI findings, were compared in these two groups. Core biopsy was performed in all patients, and in 10 of 12 patients, histopathologic evaluation of the postoperative resected specimen was also performed. RESULTS: Although all 12 tumors were benign on histopathology, four had elevated choline levels. Of these, three (75%) had an aggressive radiographic appearance (Campanacci stage 3). As opposed to this, only three of the eight (37.5%) tumors without a choline peak had an aggressive radiographic appearance. Except for a single case, all tumors showed early enhancement and washout of contrast material on dynamic MRI. CONCLUSION: The results of this study indicate that GCT of bone may show raised choline levels on proton MR spectroscopy. This finding is not an indicator of malignancy in these tumors.

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.

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.

c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas.

INTRODUCTION: MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. METHODS: Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. RESULTS: A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. CONCLUSION: IHC is not a relevant screening tool for MET abnormalities in LSC.

Spindle and giant cell type undifferentiated carcinoma arising in the common bile duct: a case report.

We report on a 61-year-old Japanese male with a pedunculated tumor in the common bile duct. The tumor consisted of two types of neoplastic cells. The majority showed atypical spindle- and giant-shaped features and proliferated densely in an inflammatory stroma, revealing a sarcomatous pattern. They expressed vimentin, KL-1, and CAM5.2. The remaining minority showed glandular and tubular features, occupied only less than 5%, located only in the tumor surface, and expressed wide spectrum keratin, KL-1, CAM5.2, epithelial membrane antigen, AE1/AE3, and carcinoembryonic antigen. CD68-positive osteoclast-like giant cells were also observed. Therefore, the patient was diagnosed as having an undifferentiated carcinoma, spindle and giant cell type.

Uncommon solid pancreatic neoplasms: ultrasound, computed tomography, and magnetic resonance imaging features.

This article reviews the ultrasound, computed tomography, and magnetic resonance imaging features of rare solid tumors of the pancreas with attention to distinctive imaging appearances, which can help radiologists to discriminate between the different entities. Various uncommon solid pancreatic neoplasms, including exocrine and endocrine epithelial tumors, mesenchymal tumors, and metastases, are reviewed, with emphasis on key differential points, including morphologic features and patterns of contrast enhancement.