A Case Report of Incomplete Carney Complex With SMARCA4-Deficient Thoracic Sarcoma: Implications for the SLC7Aaa and ARID1A Expression

Abstract Background: SWI/SNF-related, matrix-associated, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member (SMARCA4)-deficient thoracic sarcoma (SMARCA4-DTS) is a rare disease that has recently been described as an entity. It is characterized by an aggressive clinical course and specific genetic alterations. As an immunohistological feature, the tumors are deficient in SMARCA4 and SMARCA2 and express the sex-determining region Y-box 2 (SOX2). In contrast, Carney’s triad is a syndrome that combines three rare soft tissue tumors: gastric leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma, of which at least two are required for diagnosis. Both diseases are valuable case, and there have been no previous reports of their coexistence.Case presentation: A 43-year-old man visited our hospital because of respiratory distress. Computed tomography revealed a large mass measuring 55 mm in the upper lobe of his right lung and front mediastinum, with metastases in the surrounding lymph nodes. Needle biopsy was performed for diagnosis, and histological examination of the samples revealed monotonous epithelioid-like cells with loose binding and sheet-form proliferation. The tumor cells had distinct nuclei, with rhabdoid-kile cells in some locations. Immunohistochemical analysis revealed that the tumor cells were positive for SOX2, CD34, and p53 and negative for SMARCA4 and SMARCA2. The patient died 6 months after admission without any treatment. Autopsy revealed ganglioneuroma and enchondroma, suggesting an incomplete Carney complex.Conclusion: SMARCA4-DTS is a rare and recently established disease. While it is difficult to siagnose, it is necessary to distinguish undifferentiated carcinoma, large cell carcinoma, Ewing sarcoma, epithelioid sarcoma, etc. when diagnosing tumors involving the mediastinum, In addition, case with both an incomplete Carney complex and SMARCA4-DTS are very rare. We discuss and report about SMARCA4-DTS by examining the expression of AT-rich interactive domain-containing protein 1A and solute carrier family 7 member 11.

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Morphologic, Molecular and Clinical Features of Aggressive Variant Prostate Cancer

Cells ◽

10.3390/cells9051073 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1073 ◽

Cited By ~ 2

Author(s):

Rodolfo Montironi ◽

Alessia Cimadamore ◽

Antonio Lopez-Beltran ◽

Marina Scarpelli ◽

Gaetano Aurilio ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Large Cell Carcinoma ◽

Large Cell ◽

Final Diagnosis ◽

Undifferentiated Carcinoma ◽

Castration Resistant Prostate Cancer ◽

Platinum Based Chemotherapy ◽

Intermediate Part ◽

Aggressive Variant

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.

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Relationship of CA 125 and CA 19.9 with lung carcinoma histological subtype: Preliminary study

The International Journal of Biological Markers ◽

10.1177/172460088900400406 ◽

1989 ◽

Vol 4 (4) ◽

pp. 215-220 ◽

Cited By ~ 9

Author(s):

R. Molina ◽

P. Santabarbara ◽

X. Filella ◽

P. Mengual ◽

A.M. Ballesta ◽

...

Keyword(s):

Lung Cancer ◽

Large Cell Carcinoma ◽

Distant Metastases ◽

Large Cell ◽

Serum Levels ◽

Primary Treatment ◽

Undifferentiated Carcinoma ◽

Ca 125 ◽

Histological Types ◽

Ca 19.9

The aim of this work was to study the possible utility of simultaneous determination of CA 125 and CA 19.9 in patients with lung cancer. Serum levels of both markers were studied in 87 patients without metastases (Mo), 72 patients with distant metastases (MT) and 15 cases without clinical evidence of disease after primary treatment (NED). Sitxty-five tumors were epidermoid, 34 were adenocarcinomas, 24 were cell undifferentiated carcinomas and 51 were small-cell carcinomas. Sera from 75 healthy subjects and 20 patients with benign lung disease were used as controls. The cutoff values used were 35 and 37 U/ml for CA 125 and CA 19.9, respectively. CA 125 and CA 19.9 serum levels were within normal limits in all control patients. In NED patients these markers were not elevated, except in one with chronic liver disease who showed elevated CA 19.9 (76 U/ml). Twenty-five percent of Mo lung cancer patients and 40.3% of MT cases had CA 19.9 over 37 U/ml. Abnormally high levels of CA 125 were found in 18.7% and 22.9% of Mo and MT patients, respectively. Sixty percent of patients with large cell undifferentiated carcinoma had elevated CA 125 (mean 176 U/ml) compared to 15.4% of patients with all other histological types of tumors combined (54.3 U/ml, p< 0.01). CA 19.9 serum levels were also more often elevated in patients with large cell undifferentiated carcinomas (50%, 7/14 cases) than in other histological types (30%, 36/120 patients), but the difference was not statistically significant. There were no differences in CA 125 and CA 19.9 serum levels in relation to location of metastatic disease including liver. Although the sensitivity of CA 125 and CA 19.9 in lung cancer is low, they may be useful as serum markers of recurrent disease in the follow-up of patients with large cell carcinoma.

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Correlation of hENT1 expression with response and survival in non-small cell lung cancer patients treated with gemcitabine-containing chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22032 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22032-e22032

Author(s):

T. Oguri ◽

H. Achiwa ◽

H. Ozasa ◽

M. Nakao ◽

T. Uemura ◽

...

Keyword(s):

Lung Cancer ◽

Immunohistochemical Analysis ◽

Large Cell Carcinoma ◽

Large Cell ◽

Positive Staining ◽

Prognostic Impact ◽

Nucleoside Transporter ◽

Exact Test ◽

Lung Cancer Patients ◽

Third Line

e22032 Background: The most active gemcitabine uptake has been found via the human equilibrative nucleoside transporter 1 (hENT1). This study was to explore the prognostic impact of the hENT1 on response and survival in Non-small lung cancer (NSCLC) patients treated with gemcitabine-containing chemotherapy. Methods: We developed polyclonal antibody for hENT1. Then we stained hENT1 expression by immunohistochemical analysis in 24 biopsy samples of NSCLC which was formaline-fixed, paraffin- embedded tissues. We were treated with gemcitabine alone or gemcitabine-containing chemotherapy until third-line regimen. Results: They comprised 16 males and 8 females with a median age of 63 years (range 45–82 years). Seventeen patients had adenocarcinomas, six had squamous-cell carcinomas, and one had a large-cell carcinoma. All patients were treated with gemcitabine- containing chemotherapy, with 9, 12, and 3 patients receiving this as a first-, second-, and third-line therapy, respectively. The hENT1-positive staining in NSCLC samples was significantly associated with response to gemcitabine-containing chemotherapy (Fisher's exact test, P<0.05). Responses to gemcitabine-containing chemotherapy were evident in none of the seven patients with no hENT1 expression. Further 3 years survival differed by hENT1 staining: 714 days for hENT1-positive, 316 days for hENT1-negative (HR 2.86; 95%CI 1.13–15.16, P<0.05). Conclusions: While there are some determinants for gemcitabine sensitivity, hENT1 expression may be a predictive maker for the response and survival to gemcitabine-containing chemotherapy in NSCLC. No significant financial relationships to disclose.

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Resection after chemoradiotherapy of stage IIIB N3 large cell carcinoma of the lung without tumor cells remaining; a case report.

The Journal of the Japanese Association for Chest Surgery ◽

10.2995/jacsurg.9.80 ◽

1995 ◽

Vol 9 (1) ◽

pp. 80-86

Author(s):

Shin-ichirou Ohta ◽

Satoshi Ooi ◽

Hirohisa Inaba ◽

Yasuhisa Oode ◽

Yasuyuki Nagashima ◽

...

Keyword(s):

Case Report ◽

Cell Carcinoma ◽

Tumor Cells ◽

Large Cell Carcinoma ◽

Large Cell ◽

Stage Iiib

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TAMI-28. DIFFERENTIAL MIGRATION MECHANICS AND IMMUNE RESPONSES OF GLIOMA SUBTYPES

Neuro-Oncology ◽

10.1093/neuonc/noaa215.916 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii219-ii219

Author(s):

Ghaidan Shamsan ◽

Chao Liu ◽

Brooke Braman ◽

Susan Rathe ◽

Aaron Sarver ◽

...

Keyword(s):

Tumor Cells ◽

Immune Cell ◽

Molecular Subtypes ◽

Ex Vivo ◽

Brain Slices ◽

Traction Force ◽

Genetic Alterations ◽

Sleeping Beauty ◽

Brain Parenchyma ◽

Biophysical Modeling

Abstract In Glioblastoma (GBM), tumor spreading is driven by tumor cells’ ability to infiltrate healthy brain parenchyma, which prevents complete surgical resection and contributes to tumor recurrence. GBM molecular subtypes, classical, proneural and mesenchymal, were shown to strongly correlate with specific genetic alterations (Mesenchymal: NF1; Classical: EGFRVIII; Proneural: PDGFRA). Here we tested the hypothesis that a key mechanistic difference between GBM molecular subtypes is that proneural cells are slow migrating and mesenchymal cells are fast migrating. Using Sleeping Beauty transposon system, immune-competent murine brain tumors were induced by SV40-LgT antigen in combination with either NRASG12V (NRAS) or PDGFB (PDGF) overexpression. Cross-species transcriptomic analysis revealed NRAS and PDGF-driven tumors correlate with human mesenchymal and proneural GBM, respectively. Similar to human GBM, CD44 expression was higher in NRAS tumors and, consistent with migration simulations of varying CD44 levels, ex vivo brain slice live imaging showed NRAS tumors cells migrate faster than PDGF tumors cells (random motility coefficient = 30µm2/hr vs. 2.5µm2/hr, p < 0.001). Consistent with CD44 function as an adhesion molecule, migration phenotype was independent of the tumor microenvironment. NRAS and human PDX/MES tumor cells were found to migrate faster and have larger cell spread area than PDGF and human PDX/PN tumors cells, respectively, in healthy mouse brain slices. Furthermore, traction force microscopy revealed NRAS tumor cells generate larger traction forces than PDGF tumors cells which further supports our theoretical mechanism driving glioma migration. Despite increased migration, NRAS cohort had better survival than PDGF which was attributed to enhanced antitumoral immune response in NRAS tumors, consistent with increased immune cell infiltration found in human mesenchymal GBM. Overall our work identified a potentially actionable difference in migration mechanics between GBM subtypes and establishes an integrated biophysical modeling and experimental approach to mechanically parameterize and simulate distinct molecular subtypes in preclinical models of cancer.

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Primary pulmonary epithelioid sarcoma: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02940-0 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Eiki Mizutani ◽

Riichiro Morita ◽

Keiko Abe ◽

Makoto Kodama ◽

Shogo Kasai ◽

...

Keyword(s):

Tumor Cells ◽

Lung Tumor ◽

Smooth Muscle Actin ◽

Asbestos Exposure ◽

Epithelioid Sarcoma ◽

Whole Body ◽

Health Examination ◽

Positron Emission ◽

Primary Lung Tumor ◽

The Right

Abstract Background Epithelioid sarcoma most frequently occurs in the dermal or subcutaneous area of the distal extremities. To date, there have been three cases of primary pulmonary epithelioid sarcoma reported. We report a case of epithelioid sarcoma that is considered a primary lung tumor. Case presentation A 65-year-old asymptomatic Asian male patient underwent chest radiography during a routine health examination, and an abnormal mass was detected. His past medical history was unremarkable. He smoked 40 cigarettes every day and had slightly obstructive impairment on spirometry. He worked as an employee of a company and had no history of asbestos exposure. He underwent partial resection of the right lung by thoracoscopy. A histological examination of the tumor revealed a cellular nodule of epithelioid and spindle-shaped cells. Some of the tumor cells displayed rhabdoid features and reticular arrangement in a myxomatous stroma. Immunohistochemically, the tumor cells were positive for vimentin, smooth muscle actin (SMA), CD34, and epithelial membrane antigen (EMA); loss of the BAF47/INI1 protein in the tumor cells was also confirmed. A diagnosis of epithelioid sarcoma was established. Careful screening by whole-body positron emission tomography for another primary lesion after surgery did not detect any possible lesion. He had no cutaneous disease. Conclusion To our knowledge, this is the fourth case of a proximal-type epithelioid sarcoma considered as a primary lung tumor.

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