Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest diameter (mean: 4.6 cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

Programmed death ligand-1 expression levels, clinicopathologic features, and survival in surgically resected sarcomatoid lung carcinoma.

AIM: To determine the programmed death ligand-1 (PD-L1) expression rates in sarcomatoid lung carcinomas and to compare clinicopathologic features and survival rates of PD-L1-positive and negative patients. METHODS: PD-L1 expression was evaluated in 65 surgically resected sarcomatoid carcinomas. The clinicopathologic features of cases with PD-L1-positive and negative tumors were compared. Kaplan-Meier survival analysis was performed. Multiple Cox proportional hazard regression analysis was performed to determine independent predictors of overall survival. RESULTS: PD-L1 antibody positivity was found in 72.3% of surgically resected sarcomatoid lung carcinomas. Regarding histopathologic subtypes, PD-L1 expression was positive in 80.4% of pleomorphic carcinomas, 62.5% of spindle- and/or giant-cell carcinomas, and 16.7% of carcinosarcomas. Pleural invasion was observed in 68.1% of PD-L1-positive cases and 27.8% of PD-L1-negative cases (P = 0.008). No difference in survival was found between PD-L1-positive and -negative tumors. The only factor significantly associated with poor survival was the pathological stage of the tumor. CONCLUSIONS: This study reveals a high rate of PD-L1 positivity in a large number of sarcomatoid lung carcinoma cases with pleomorphic carcinoma, spindle- and/or giant-cell carcinoma, and carcinosarcoma subtypes. The only significantly different clinicopathologic feature in PD-L1-positive cases is pleural invasion. PD-L1 positivity is not a significant predictor of survival in sarcomatoid lung carcinomas.

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.

Pleomorphic giant cell carcinoma of the urinary bladder.

In this report, we present the clinicopathologic features of 8 cases of the pleomorphic giant cell variant of urothelial carcinoma. This is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The pleomorphic giant cell component varied from 20% to 100% of the tumor specimen; in 2 cases, the pleomorphic giant cell component composed greater than 50% of the tumor with 1 case showing pure pleomorphic giant cell carcinoma. The architectural pattern of the tumor varied from infiltrating pleomorphic tumor with bizarre giant cells to solid expansile nests with discohesive growth pattern; a hypocellular desmoplastic stromal response was present in 2 cases (25%) with single cells in sclerotic stroma. At histology, giant, bizarre, anaplastic cells with frequent typical or atypical mitotic figures were present in all cases. Seven mixed cases had concurrent conventional high-grade urothelial carcinoma; 2 cases presented features of micropapillary or lymphoepithelioma-like urothelial carcinoma. Variable size intracytoplasmic vacuoles were present in 2 cases. All patients had advanced-stage cancer (>/=pT3), and 6 (75%) had lymph node metastases. Immunohistochemical staining demonstrated that both pleomorphic giant cell and associated conventional urothelial carcinoma were positive for cytokeratins 7, CAM 5.2 and AE1/AE3, and epithelial membrane antigen; P63, thrombomodulin, and uroplakin III were positive in 6, 3, and 2 cases, respectively. Follow-up information was available in all cases (range, 6-74 months; mean, 20 months). Five of the patients died of disease from 6 to 17 months, and 2 patients were alive with metastases at 11 and 19 months. One patient had no evidence of disease at 74 months. In summary, pleomorphic giant cell is an aggressive variant of urothelial carcinoma associated with poor prognosis that presents at an advanced clinical stage. In limited samples, it may be misdiagnosed as secondary carcinoma or sarcoma, a pitfall of paramount importance for its clinical management.

Personal experience in surgical management of pulmonary pleomorphic carcinoma.

BACKGROUND: Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary pleomorphic carcinoma was introduced by the 1999 World Health Organization classification as a new peculiar type of lung carcinoma showing concurrent malignant epithelial and sarcomatoid spindle cell elements. Few reports describe its clinical behavior. My colleagues and I report a series of patients surgically treated for pulmonary pleomorphic carcinoma to describe our experience with this malignant neoplasm. METHODS: Twenty cases of pleomorphic pulmonary carcinoma were collected and studied clinicopathologically. All patients underwent surgical resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA. Histologic diagnosis was established by using light microscopic examination and immunohistochemistry. Survival rates were calculated with the Kaplan-Meier method. RESULTS: We postoperatively diagnosed 20 cases of pleomorphic carcinoma: 14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0. The remaining 16 patients died from early distant metastases. The median duration of disease-free survival was 5 months. The median duration of overall survival was 8 months. CONCLUSIONS: The prognosis of patients with pleomorphic carcinoma was poor, despite surgery and adjuvant chemotherapy, because of early relapse of disease. Nodal involvement was a determinant prognostic variable, because advanced stages were related to worse prognosis. In case of preoperatively proven pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients.

Anaplastic giant cell carcinoma of the thyroid gland: treatment and survival over a 25-year period.

Anaplastic giant cell carcinoma of the thyroid is a rare but highly malignant tumor. At the Karolinska Hospital in Stockholm, surgery, chemotherapy, and radiotherapy have been used separately or in various combinations in 81 patients admitted with this diagnosis during 1971-1997. In this study, we present the various multimodality treatment regimens and their changes over the years and the subsequent differences in survival and local tumor control. Overall, eight patients (10%) survived more than 2 years. All survivors were treated with combinations of chemotherapy, radiotherapy, and surgery. Among the patients who died, local tumor control was achieved by the therapy given in many cases. The results suggest that our current strategy with a combination of preoperative hyperfractionated accelerated radiotherapy, doxorubicin pre- and postoperatively, and debulking surgery whenever possible results in better local tumor control and an increased chance of survival.

Spindle and giant cell carcinoma of the urinary bladder: a clinicopathological light microscopic and immunohistochemical study.

OBJECTIVE: To evaluate the cellular nature and biological behaviour of spindle and giant cell carcinoma (SGCC) of the urinary bladder. The clinicopathological, light microscopic and immunohistochemical features of seven patients are reported. PATIENTS AND METHODS: Paraffin-embedded tissue was available from each patient for microscopic and immunohistochemical studies. There were five men and two women, ranging in age from 48 to 79 years. Clinical histories and follow-up information were obtained by review of the patients' charts. The clinical outcome was compared with that of transitional cell carcinoma (TCC) and small cell carcinoma (SCC). RESULTS: The tumours were large, polypoid and frequently ulcerated. They diffusely permeated the bladder musculature or the perivesical fat. On microscopic examination five tumours were composed mainly of interlacing sheets of spindle cells and occasional giant cells; two comprised giant cells only. Foci of identifiable TCC (papillary or in situ) were present in four tumours. Immunohistochemistry demonstrated that SGCCs exhibit a phenotype indicative of an epithelial nature. CONCLUSIONS: The median survival (11 months) of the seven patients indicates that SGCCs have a poor prognosis and they are more aggressive than TCCs of the same stage. The unfavourable clinical course is similar to the rapidly fatal outcome of small cell carcinomas of the bladder. The prolonged survival periods of three patients who received additional chemotherapy suggest that this treatment may be profitable.

Anaplastic carcinoma of the thyroid: a 24-year experience.

BACKGROUND: Anaplastic carcinoma of the thyroid gland is a lethal entity; few patients live more than 12 months following diagnosis. We retrospectively reviewed the experience with this entity at our cancer institute and identified a subgroup of patients with complete resection who have a 60% 5-year survival. METHODS: Twenty-one cases of anaplastic carcinoma of the thyroid gland were analyzed retrospectively with respect to prognostic factors influencing survival. This represents 2.7% of 771 cases of thyroid cancer seen at our institution from 1968 to 1992. The median age at presentation was 65.1 years; male/female ratio was 1:1.1; and the most common symptom was a rapidly enlarging neck mass (76%). RESULTS: Estimated 5-year survival was 10% (median: 4.5 months). Tumor size less than 6.0 cm (p = .004) and female gender (p = .02) were significant prognostic factors. Five patients who underwent complete resection had an estimated 5-year survival of 60% (median: 131 months). Four of these patients had postoperative radiotherapy with or without sequential chemotherapy. Two of these patients survived more than 10 years, and a third remains alive without disease at 26 months.

Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases.

BACKGROUND: The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. METHODS: Seventy-eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow-up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. RESULTS: The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow-up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23-month mean survival (median, 10 months) (Kaplan-Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. CONCLUSIONS: The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma.