Should Small Cell Carcinoma of the Cervix be Treated As Localized Small Cell Cancer or Advanced Cervical Cancer: A Retrospective Multi-Institutional Cohort Study

Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response including PD-L1 expression and the quantity and location of tumor-infiltrating lymphocytes (TILs) in 12 small-cell and 69 “classical” urothelial cancers by immunohistochemistry. The analysis revealed that small-cell carcinomas were characterized by the virtual absence of PD-L1 expression and an “immune-excluded” phenotype with only a few TILs in the center of the tumor (CT). In small-cell carcinomas, the average immune cell density in the CT (CD3: 159±206, CD8: 87±169 cells/mm2) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625±800, p<0.001; CD8: 362±626 cells/mm2, p=0.004) while there was no significant difference in the immune cell density at the invasive margin (IM) (small-cell carcinomas CD3: 899±733, CD8: 404±433 cells/mm2; urothelial carcinomas CD3: 1167±1206, p=0.31; CD8: 582±864 cells/mm2, p=0.27). Positive PD-L1 staining was found in 39% of urothelial cancers, but in only 8% of small-cell bladder cancer cases (p=0.04). Concordant with these data, a sharp decrease of PD-L1 positivity from >80% to 0% positive cells and of TILS in the CT from 466-1063 CD3-positive cells/mm2 to 50-109 CD3-positive cells/mm2 was observed in two cancers with clear-cut progression from “classical” urothelial to small-cell carcinoma. In conclusion, these data demonstrate that small-cell bladder cancer commonly exhibits an immune-excluded phenotype.

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Expression of cadherins, p53, and BCL2 in small cell carcinomas of the cervix: Potential tumor suppressor role for N-cadherin

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200303000-00024 ◽

2003 ◽

Vol 13 (2) ◽

pp. 240-243 ◽

Cited By ~ 1

Author(s):

T. A. Zarka ◽

A. C. Han ◽

M. I. Edelson ◽

N. G. Rosenblum

Keyword(s):

Tumor Suppressor ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Cell Cancer ◽

Small Cell ◽

Specific Cell ◽

Nuclear Staining ◽

Cytoplasmic Staining ◽

Significant Difference ◽

E Cadherin

Cadherins are tissue-specific cell adhesion molecules that function as tumor suppressors. Analysis of cadherin expression is useful for differentiation of tumor histogenesis, and because they serve as markers of tumor behavior and prognosis. Since the pattern of cadherin expression is not well characterized for small cell carcinoma of the cervix, we examined cases of these tumors for expression of cadherins, and two other oncoproteins p53 and BCL2. Four cases of small cell neuroendocrine carcinomas were identified from the Gynecologic Oncology Service with diagnoses confirmed by immunohistochemistry for neuroendocrine markers. Archival paraffin blocks were studied by heat-enhanced immunohistochemistry using commercially available antibodies specific for E-cadherin, P-cadherin, and N-cadherin, p53, and BCL2. Sections were examined for specific membrane staining of cadherins, nuclear staining of p53, and cytoplasmic staining of BCL2. E-cadherin was expressed in three of four cases, P-cadherin in one of four, and N-cadherin in none of four cases. P53 was expressed in one of four cases and BCL2 in one of four cases. The four cases showed three different patterns of immunohistochemical staining for the five oncoproteins. Specifically, two cases expressed E-cadherin only; one case lacked all three cadherins, was negative for BCL2, and was only positive for p53; and one case expressed E- and P-cadherin and BCL2. Prior studies of other neuroendocrine and small cell tumors of other organs showed E-cadherin expressed in 98% (42 /43), N-cadherin in 65% (28/43), and P-cadherin in 40% (17/43) of cases. Additionally, one case of vaginal small cell carcinoma showed expression of all three cadherins. The only significant difference between cervical primaries and other primary sites is that N-cadherin was not detected in our four cases vs. 65% expression in other sites (P < 0.001). We conclude that cadherin and oncoprotein profiles in small cell carcinoma of the cervix are different in the four cases analyzed. Additional cases need to be studied to determine the specificity and frequency of these oncoprotein profiles for small cell carcinoma of the cervix. These may possibly represent different oncogenic pathways in development of small cell cancer of the cervix. Also, our results suggest that N-cadherin may be a tumor suppressor gene in these tumors.

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Secondary small cell carcinoma of the endometrium after concurrent chemoradiotherapy for cervical cancer: a rare case

European Journal of Gynaecological Oncology ◽

10.31083/j.ejgo.2020.01.4813 ◽

2020 ◽

Vol 41 (1) ◽

pp. 142

Keyword(s):

Cervical Cancer ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Rare Case ◽

Concurrent Chemoradiotherapy ◽

Small Cell

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Case Report: Systemic Treatment and Serial Genomic Sequencing of Metastatic Prostate Adenocarcinoma Progressing to Small Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.732071 ◽

2021 ◽

Vol 11 ◽

Author(s):

XiaoJun Lu ◽

Wenwen Gao ◽

Yu Zhang ◽

Tao Wang ◽

Hongliang Gao ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Carcinoma ◽

Seminal Vesicle ◽

Small Cell Carcinoma ◽

Cell Cancer ◽

Phylogenetic Reconstruction ◽

Neuroendocrine Differentiation ◽

Small Cell ◽

Castration Resistance ◽

Tumor Biopsy

Small cell carcinoma (SCC)/neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive subtype of prostate cancer associated with an AR(androgen receptor)-null phenotype and visceral metastases. This study presents a 44-year-old man originally diagnosed with metastatic hormone-sensitive prostatic adenocarcinoma. After 6-month androgen deprivation therapy (ADT) combined with docetaxel, the patient developed paraplegia. Laminectomy was performed, and a thoracic vertebral biopsy revealed neuroendocrine differentiation and mixed adenocarcinoma. The patient developed liver metastases and experienced stable disease for 4 months following etoposide combined with cisplatin and pembrolizumab. Seminal vesicle biopsy after chemotherapy revealed small-cell cancer. The prostate biopsy specimen also indicated pure SCC. We witnessed the dynamic evolution from pure adenocarcinoma to fully differentiated SCC, leading to obstruction and death. In addition, whole-exome sequencing was performed on both biopsy specimens of the thoracic vertebra at the beginning of castration resistance and that of seminal vesicle after multiple lines of treatment failure. Utilizing phylogenetic reconstruction, we observed that both samples shared a common ancestor clone harboring aberrations in the TP53, RB1, and NF2 genes. We also discovered that driver events in the private subclones of both samples, such as alterations in CDC27 and RUNX1, might have played a significant role in tumor progression or even neuroendocrine differentiation. Tumor biopsy and IHC assessment must be repeated at different stages of progression, because of intrapatient spatial and temporal heterogeneity of adenocarcinoma versus SCC/NEPC. Although, typical treatments including ADT, docetaxel, etoposide, cisplatin, and pembrolizumab provided temporary response, the patient still had a poor prognosis.

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Gynecologic Cancer InterGroup (GCIG) Consensus Review for Small Cell Carcinoma of the Cervix

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000262 ◽

2014 ◽

Vol 24 (Supp 3) ◽

pp. S102-S108 ◽

Cited By ~ 43

Author(s):

Toyomi Satoh ◽

Yuji Takei ◽

Isabelle Treilleux ◽

Mojgan Devouassoux-Shisheboran ◽

Jonathan Ledermann ◽

...

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Early Stage ◽

Gynecologic Cancer ◽

Uterine Cervical Cancer ◽

Small Cell ◽

High Incidence ◽

Review Current

AbstractSmall cell carcinoma of the cervix (SCCC) is a rare histological entity of uterine cervical cancer. Compared with other common histological types, squamous cell carcinoma or adenocarcinoma, the outcome of SCCC is poor because of the high incidence of nodal or distant metastasis even with early stage. In this review, current consensus of epidemiology, pathology, and initial treatment for SCCC will be discussed.

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The expression and clinical significance of clusterin and ki67 in cervical cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16554 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16554-e16554

Author(s):

E. Shrestha

Keyword(s):

Cervical Cancer ◽

Cell Carcinoma ◽

Clinical Significance ◽

Small Cell Carcinoma ◽

Squamous Epithelium ◽

Small Cell ◽

Cancer Center ◽

Ki67 Expression ◽

Significant Difference ◽

Expression Rate

e16554 Background: To explore the expression pattern and clinical significance of the CLU and proliferation indices ki67 in cervical cancer. Methods: 59 cases treated at Cancer Center Sun Yat-sen University during 1989–2006 were enrolled in the study group. The relationship was analyzed for the expressions of CLU and Ki67 with clinical factors. Results: In this study positivity of CLU in cervical SCC, 10% (3/31) cases weak positive, adenocarcinoma 21% (4/19) weak positive in small cell carcinoma 11% (1/9) moderate positive. Control groups, CLU weak positive expression, 21% (3/14) CIN 2–3 and 14% (2/13) normal squamous epithelium.CLU expression found 100% (31/31) normal endocervical glands.The Ki67 in SCC 13% (4/31) cases weak positive and 5% (1/19) adenocarcinoma. All cases small cell carcinoma revealed negative. No significant difference of the CLU expression rate between normal cervical epithelium, CIN II-III and SCC (p = 0.561). No significant difference of CLU expression rate between normal endocervical gland and adenocarcinoma (p = 0.119) as well. In Ki67, there was no significant difference of Ki67 rates between CIN 2–3 and normal squamous epithelium (p = 0.585). No significant difference of Ki67 expression rates between adenocarcinoma and normal squamous epithelium (p = 0.341). The expression of CLU and Ki67 had no correlation with FIGO stage, SCC antigen level, grade of differentiation, deep stromal invasion, and lymph node metastasis. Finally, the expression of CLU and Ki67 was not related to the 5-years DFS rates, and CLU expression was not correlated with Ki67 expression (rs = 0.500, p = 0.391). Conclusions: CLU and Ki67 was in lower rates in cervical cancer, and was not associated with any clinicopathological features. It is suggested that CLU and Ki67 have no distinct role in carcinogenesis. The further larger studies are needed to verify the results of this study. No significant financial relationships to disclose.

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Extra-pulmonary small cell carcinoma of the neopharynx: case report and review of neopharyngeal tumours after total laryngectomy

The Journal of Laryngology & Otology ◽

10.1017/s0022215109990697 ◽

2009 ◽

Vol 124 (2) ◽

pp. 216-219 ◽

Cited By ~ 1

Author(s):

A George ◽

H Uppal ◽

C Phelan ◽

R Hughes

Keyword(s):

Case Report ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

World Literature ◽

Treatment Options ◽

Cell Cancer ◽

Small Cell ◽

The World ◽

Extra Pulmonary ◽

Distant Spread

AbstractObjective:We report the first documented case in the world literature of primary extra-pulmonary small cell carcinoma occurring in the neopharynx following laryngectomy.Method:We present a case report and a review of the world literature regarding the management of tumours of the neopharynx and extra-pulmonary small cell carcinoma.Results:The paucity of cases of extra-pulmonary small cell carcinoma has resulted in many departments managing this neoplasm similarly to pulmonary small cell cancer. However, the site of the primary can have an impact on disease survival and treatment options.Conclusion:Neopharyngeal small cell carcinoma has not previously been reported. It should be managed in the same way as other extra-pulmonary small cell carcinomas occurring within the pharynx or larynx, with combined multi-drug chemotherapy and radiotherapy. Surgery has a limited role due to the aggressiveness of the disease and the high risk of local and distant spread at presentation.

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Diagnosis and Treatment of Small Cell Carcinoma of the Larynx: A Critical Review

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348948609500610 ◽

1986 ◽

Vol 95 (6) ◽

pp. 590-600 ◽

Cited By ~ 40

Author(s):

Alfio Ferlito

Keyword(s):

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Ductal Carcinoma ◽

Cell Cancer ◽

Small Cell ◽

Malignant Neoplasms ◽

Microscopic Appearance ◽

First Case ◽

Laryngeal Mucosa ◽

Carcinoma Of The Larynx

Small cell carcinoma of the larynx is an uncommon neuroendocrine tumor with particular pathologic, therapeutic, and prognostic connotations. The first case of this lesion was observed in Canada in 1972. Fourteen cases of small cell carcinoma of the larynx were observed in the Ear, Nose, and Throat Department of Padua University in a series of 3,284 primary and secondary laryngeal and hypopharyngeal malignant neoplasms. This number constitutes the largest collection from a single institution in the literature and brings the total recorded cases to 66. The tumor is thought to arise from the argyrophilic Kulchitsky cells normally found in laryngeal mucosa. The diagnosis is based on the light microscopic appearance of the neoplasm and can be confirmed by electron microscopy. The differential diagnosis must be made from carcinoid, atypical carcinoid, small cell squamous carcinoma, small cell ductal carcinoma, lymphoma, mycosis fungoides, and metastatic lung small cell cancer. Systemic chemotherapy with radiation therapy is the accepted manner of treatment today. The survival of the patients treated with these modalities may be significantly improved, and some patients may be cured.

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