Poorly differentiated thyroid carcinoma with pleomorphic giant cells-a case report.

Poorly differentiated thyroid carcinoma (PDTC) refers to a malignant tumour that displays an intermediate prognosis between well-differentiated carcinomas and anaplastic thyroid carcinomas (ATC). In the thyroid, pleomorphic giant cells are observed in ATC or in some non-neoplastic thyroid diseases. We described the case of a 43-year-old woman with a 34-mm nodule in her thyroid right lobe. Microscopic examination revealed an encapsulated tumour with a main solid growth pattern and extensive capsular invasion. Multiple images of angioinvasion were observed. There was neither necrosis nor inflammation. Most of the tumour cells were medium-sized and intermingled with pleomorphic giant tumour cells with bizarre features. The immunoprofile (keratins +, TTF1+, Pax 8+) proved their thyroid origin. By NGS, no molecular alteration was identified. The patient was treated by surgery and radioiodine therapy and she has no recurrence after a follow-up of 24 months. Our case meets all the histological criteria of the Turin proposal for PDTC but with pleomorphic giant cells and is very different from ATC according to clinical, histological and immunohistochemical features. Pleomorphic tumour giant cells in thyroid carcinomas could be present in PDTC and do not always represent dedifferentiation and more aggressive carcinoma, thyroid neoplasm.

Prostatic Adenocarcinoma With Focal Pleomorphic Giant Cell Features: A Series of 30 Cases.

Prostatic adenocarcinoma with focal pleomorphic giant cell features is rare with the only prior series consisting of 6 cases. From 2005 to 2018, we identified 29 cases from our consult service and 1 case from our own institution. Men ranged in age from 39 to 90 years (median=75.5). Diagnostic specimens consisted of needle biopsies (n=13); transurethral resections (n=7), urethral/bladder biopsies (n=8), radical prostatectomy (n=1), and orchiectomy (n=1). In all cases, there was usual acinar prostatic adenocarcinoma, where the highest grade in all cases was Gleason score 9 to 10 (Grade Group 5). On average, 68% of the involved cores had cancer with a maximum percent of cancer averaging 55%; on average, transurethral resections had 85% of the area involved by cancer. Areas of cancer showing pleomorphic giant cell features were focal (<5%). Two of the needle biopsies showed extraprostatic extension. The radical prostatectomy had seminal vesicle invasion and positive margins with lymphovascular invasion. Prostatic adenocarcinoma with focal pleomorphic giant cell features is always accompanied by extensive usual acinar prostate adenocarcinoma where the highest grade in all cases was Gleason score 9 to 10 (Grade Group 5). Although the pleomorphic component is focal, it can mimic urothelial carcinoma. IHC can be misleading as PSA staining is often negative or focal in both the pleomorphic and usual prostatic adenocarcinoma components. NKX3.1 is the most sensitive prostate marker, but was still focal in 1 usual prostatic adenocarcinoma and negative in 2 pleomorphic components. Prostatic adenocarcinoma with focal pleomorphic giant cell features has a dismal prognosis. In men with no prior diagnosis of prostate adenocarcinoma and >1-year follow-up, 7/19 (37%) were dead at a median of 8 months after diagnosis. Of the 7 men with a prior history of prostate adenocarcinoma, 4/7 (57%) were dead at a median of 7 months after diagnosis of recurrent prostate adenocarcinoma with pleomorphic giant cell features.

Histomolecular profiling of pleomorphic, spindle cell, and giant cell carcinoma of the lung for targeted therapies.

In pleomorphic, spindle cell, and giant cell carcinoma (PSCGC) of the lung, we wondered if an integrated diagnosis including morphological and immunohistochemical features could be related to molecular status. We performed immunohistochemistry on 35 PSCGCs against TTF1, napsin A, p40, ALK, ROS1, and c-MET. Mutational status regarding EGFR, KRAS, BRAF, HER2, and PIK3CA genes was established. Of 18 PSCGCs with adenocarcinomatous or "undifferentiated" carcinoma differentiation, 8 were mutated for EGFR (n = 1), KRAS (n = 2), BRAF (n = 1), HER2 (n = 3), and PIK3CA (n = 1). No PSCGC (0/4) with only squamous cell or adenosquamous (0/2) differentiation was mutated. c-MET overexpression was only seen in PSCGC with adenocarcinomatous or undifferentiated component (n = 5) without squamous cell component. ROS1 and ALK were negative. The presence of a "targetable mutation" was correlated to the presence of morphological or immunohistochemical adenocarcinomatous differentiation (P = .0137). Integrated diagnosis of an adenocarcinomatous component in PSCGC could be associated with the presence of targetable gene mutation. Because only PSCGC with adenocarcinomatous or undifferentiated carcinoma harbors mutations, whereas PSCGC with only squamous or adenosquamous differentiation does not in our study, this might represent a prescreening for patients with PSCGC to be tested for molecular targets. Our results emphasize that careful morphological examination and the use of immunohistochemistry might be useful for the selection of PSCGC tested for a mutational target.

Characteristics and Prognostic Analysis of 69 Patients With Pulmonary Sarcomatoid Carcinoma.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy. METHODS: A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis. RESULTS: PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (≥18.5), with normal hemoglobin, with smaller tumor size (≤4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05). CONCLUSIONS: PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.

Mammary carcinoma with osteoclast-like giant cells: a case report.

Mammary carcinoma with osteoclast-like giant cells is rare, and comprises less that 2% of breast carcinoma cases. Herein, we present a case of a 45-year-old woman who underwent breast lumpectomy and sentinel lymph node biopsy for a solitary well defined breast tumor. Histological examination revealed an invasive tumor composed of ducts, small nests and cribriform formations intermixed with a prominent osteoclast like giant cell component. The background stroma is hemorrhagic with conspicuous hemosiderin deposition. The paper will outline the clinico-pathologic characteristic features of this uncommon subtype as well as the current understanding on the pathogenesis of the osteoclast-like giant cells. The invasive carcinoma and the osteoclast-like giant cells staining patterns using immunohistochemical stains for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, receptor activator of nuclear-kB, RANK ligand, and matrix metalloproteinase 1 are reported.

Polyomavirus (BK)-associated pleomorphic giant cell carcinoma of the urinary bladder: a case report.

This report describes the morphological features of a pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder in a male, 12 years post living related donor renal transplant. The voided urine cytology demonstrated rare decoy cells admixed with markedly atypical urothelial cell clusters, papillae and giant cells. Cystoprostatectomy demonstrated a nodular mass involving the trigone and right lateral-posterior wall, adjacent to the ureteral orifice. Hematoxylin-eosin stained sections showed two synchronous malignancies: (a) pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder, metastatic to the omentum and (b) prostatic adenocarcinoma, Gleason score 3+4=7, involving the right prostate lobe. Strong diffuse expression of polyomavirus large T antigen was demonstrated in the primary and metastatic pleomorphic giant cell carcinoma, supporting a possible role for polyomavirus (BK) in the oncogenetic pathway. The prostatic adenocarcinoma was negative for polyomavirus large T antigen. Our findings of p63, CK7 and CK903 expression in pleomorphic giant cell carcinoma suggest that the tumor is of urothelial derivation. This is the first report describing the morphological features of urinary bladder pleomorphic giant cell carcinoma with trophoblastic differentiation, positive for polyomavirus large T antigen, arising in the background of BKV reactivation.

[Pulmonary sarcomatoid carcinoma]. / Carcinomes sarcomatoïdes pulmonaires.

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about 1 % of non-small cell lung carcinoma (NSCLC). In 2004, World Health Organization classification united under this name all the carcinomas with sarcomatous or sarcomatous-like component with spindle cell or giant cell appearance. There are five subtypes: spindle cell carcinoma, giant cell carcinoma, pleomorphic carcinoma, carcino-sarcoma and pulmonary blastoma. Clinical characteristics are not specific from the others subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastasis are frequent with atypical locations such as peritoneal or retroperitoneal sites. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here, we present a review of litterature in order to better describe these tumors.

Sarcomatoid carcinoma of the stomach with osteoclast-like giant cells.

Carcinomas with osteoclast-like giant cells (OGCs) are a rare type of malignant tumor that is histologically characterized by the presence of multinucleated giant cells that resemble osteoclasts mixed with poorly differentiated adenocarcinoma cells. In this study, we report the clinicopathological and immunohistochemical features of a gastric sarcomatoid carcinoma with OGCs in a 37-year-old male. An abdominal CT scan demonstrated a large mass, measuring 15 cm × 10 cm, in the lesser curvature of the stomach. Microscopic examination revealed that the tumor was composed of sarcomatoid and carcinomatous elements with infiltrating OGCs. Immunohistochemical analysis showed that the sarcomatoid and carcinomatous elements were both variably positive for CK7 and EMA. The sarcomatoid components were also vimentin and SMA positive. This is the first report of a gastric sarcomatoid carcinoma with OGCs. The present tumor has progressed rapidly with extensive perigastric involvement and multiple intrahepatic metastases.

Two cases of breast carcinoma with osteoclastic giant cells: are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

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.

Review article: pulmonary sarcomatoid carcinomas: a practical overview.

Pulmonary sarcomatoid carcinomas (PSCs) are currently defined as poorly differentiated non-small-cell carcinomas containing a component with sarcoma or sarcoma-like (spindle and/or giant cell) features. They consist of 5 major histological variants, namely pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. The segregation of PSCs into a distinct clinicopathologic entity seems justified on the basis of morphologic, behavioral, and genotypic/phenotypic attributes. As a group, PSCs generally run an aggressive clinical course and may cause major difficulties in the differential diagnosis with other primary and secondary malignancies of the lung. At present, PSCs are believed to represent a family of carcinomas "in transition," in which diverse pathways of clonal evolution account for histological differences of a common ancestor lesion. The sarcomatous or sarcomatoid component of these tumors is thought to derive from carcinoma cells during the progression of carcinogenesis through the activation of an epithelial-mesenchymal transition program leading to sarcomatous transformation or metaplasia (conversion paradigm). Conceivably, targeting the epithelial-mesenchymal transition program could become a valid therapeutic strategy for these life-threatening tumors, whose sensitivity to current medical manipulation is disappointing.

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.

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.

Primary peritoneal anaplastic giant cell carcinoma: case report of an unusual and highly malignant müllerian neoplasm.

Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical müllerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peritoneum as a primary tumor.

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.

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.

[Pathological study of the pleomorphic carcinoma of the lung].

OBJECTIVE: A clinicopathological study of 10 patients with pleomorphic carcinoma of the lung. METHODS: Histopathological and immunohistochemical staining for keratin, vimentin, Mac387, desmin, actin and S-100 protein were used for this study. RESULTS: Pleomorphic carcinoma of the lung was found to often occur in males above 50 years of age and with clinical symptoms including cough, expectoration, haemoptysis and chest pain. The most frequent microscopic diagnosis was squamous cell carcinoma, and adenocarcinoma, accompanied by spindle and giant cells. The epithelial component of pleomorphic carcinoma of the lung displayed positivity for keratin and the spindle cells displayed positivity for vimentin. In some cases the neoplastic epithelial component and spindle cells showed positive expression of both keratin and vimentin. CONCLUSION: Pleomorphic carcinoma of the lung may display various histopathological changes making it easy to be misdiagnosed as carcinosarcoma. Understanding its pathogenesis and histopathology is important for the diagnosis and differential diagnosis.

Supratentorial giant cell ependymoma: a case report.

Ependymomas are neoplasms of the central nervous system that are capable of demonstrating remarkably heterogeneous histologic features. These tumors originate from ependymal cells lining the ventricles, the choroid plexus, the central canal of the spinal cord, and the filum terminale, so they are therefore seen throughout the neuraxis. We describe the case of a 26-year-old man who experienced a 3-week history of right-sided numbness and a 1-week history of worsening bifrontal headache. Computed tomographic scanning and magnetic resonance imaging of his head demonstrated an irregularly enhancing mass involving the left medial frontal lobe, with extension across the corpus callosum and expansion into the body and atrium of the left lateral ventricle. Histologic, immunohistochemical, and electron microscopic findings were consistent with an anaplastic ependymoma. Unique to this neoplasm was the presence of multiple tumor giant cells. The presence of pleomorphic tumor giant cells is a characteristic feature of the subependymal giant cell astrocytoma, and it is also commonly seen in pleomorphic xanthoastrocytoma and glioblastoma multiforme. Bizarre giant cells were recently described in two filum terminale ependymomas. This report presents the first case of a supratentorial giant cell ependymoma with anaplastic features.