So-Called Serous Carcinoma of the Uterine Cervix with BRCA2 Mutation: Case Report and Review of the Literature

Serous carcinoma of the uterine cervix (SCUC) is now believed to be a morphological variant of an HPV-associated endocervical adenocarcinoma or a metastasis from a serous carcinoma of the upper tract. In terms of mutational status as detected by next-generation sequencing (NGS), this controversial entity has not been characterized yet. We describe the case of a patient with a carcinoma categorized as stage IVB SCUC, initially treated with carboplatin, paclitaxel, and bevacizumab, followed by maintenance with bevacizumab. After locoregional progression, radiotherapy was administered. Unfortunately, further progression was observed, and carboplatin was resumed. Considering the presence of a <i>BRCA2</i> mutation as detected by NGS, treatment with a PARP inhibitor (olaparib) was decided and allowed disease control for 6 months. We believe that <i>BRCA</i> mutation may be systematically searched in patients suffering from carcinomas formerly referred to as SCUC and that targeted treatments should be considered.

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Next-generation sequencing-based BRCA testing on cytological specimens from ovarian cancer ascites reveals high concordance with tumour tissue analysis

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-206127 ◽

2019 ◽

Vol 73 (3) ◽

pp. 168-171 ◽

Cited By ~ 1

Author(s):

Caterina Fumagalli ◽

Alessandra Rappa ◽

Chiara Casadio ◽

Ilaria Betella ◽

Nicoletta Colombo ◽

...

Keyword(s):

Ovarian Cancer ◽

Next Generation Sequencing ◽

Clinical Decision Making ◽

Parp Inhibitor ◽

Clinical Decision ◽

Tumour Tissue ◽

Next Generation ◽

High Concordance ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

BackgroundWith the approval of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for newly diagnosed, breast cancer gene (BRCA)1/2 mutated, ovarian cancer women, the assessment of BRCA1/2 tumour status will be shortly required at the time of diagnosis.AimTo investigate the feasibility of next-generation sequencing (NGS)-based BRCA tumour test on cytological specimens from ovarian cancer ascites.MethodsWe evaluated the BRCA1/2 status on neoplastic ascites and corresponding tumour tissue of 11 patients with ovarian cancer, using the NGS ‘Oncomine BRCA Research Assay’.ResultsThe NGS-based BRCA test on cytological samples had a success rate of 100%, with 11 of 11 concordant BRCA1/2 results between ascites and tumour tissues analyses, including two wild type samples and nine cases harbouring somatic or germline variants.ConclusionBRCA test may be performed on ovarian cancer ascites, reproducing BRCA1/2 tumour status and representing a useful tool for clinical decision-making.

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Immunohistochemical characterization of endocervical papillary serous carcinoma

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200602001-00046 ◽

2006 ◽

Vol 16 (Suppl 1) ◽

pp. 286-292 ◽

Cited By ~ 8

Author(s):

S. Nofech-Mozes ◽

G. Rasty ◽

N. Ismiil ◽

A. Covens ◽

M. A. Khalifa

Keyword(s):

Carcinoembryonic Antigen ◽

Uterine Cervix ◽

Serous Carcinoma ◽

Control Group ◽

Fallopian Tubes ◽

Endocervical Adenocarcinoma ◽

Conventional Cell ◽

Papillary Serous Carcinoma ◽

Histologic Subtypes

Endocervical adenocarcinomas are rare and aggressive neoplasms. Papillary serous endocervical adenocarcinomas are the rarest form of endocervical adenocarcinomas. This tumor exhibits morphologic similarities to its counterparts commonly seen in the endometrium, fallopian tubes, ovaries, and peritoneum, which are known to have an aggressive behavior. Because of the rarity of this tumor, little is known about its immunophenotyping. In this study, we included ten cases of papillary serous carcinomas arising from the uterine cervix (PSCC) diagnosed in the absence of a primary endometrial malignancy. We studied their immunohistochemical profile, using a panel of antibodies against Ki67, bcl-2, p53, carcinoembryonic antigen (CEA), and CD10, and compared them to 20 consecutive cases of cervical adenocarcinoma of conventional cell subtypes (CAC) (15 mucinous, 3 adenosquamous, and 2 endometrioid). Immunostaining was recorded semiquantitatively. Patients with PSCC ranged in age from 27 to 79 years (mean = 51.6 ± 19.1), while the conventional cell subtypes control group were 28–90 years old (mean = 47.5 ± 16.9). Only p53 and CEA immunostaining significantly correlated with the PSCC morphology (P= 0.001 and P= 0.016, respectively) as shown by Cochran–Mantel–Haenszel Statistics (Modified Ridit Scores). PSCC is a distinctive immunophenotypic subtype of endocervical adenocarcinoma with significantly higher p53 and lower CEA reactivity than other more common histologic subtypes.

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Evaluation of KRAS, NRAS and BRAF mutational status and microsatellite instability in early colorectal carcinomas invading the submucosa (pT1): towards an in-house molecular prognostication for pathologists?

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-206496 ◽

2020 ◽

Vol 73 (11) ◽

pp. 741-747 ◽

Cited By ~ 1

Author(s):

Amélie Bourhis ◽

Caterina De Luca ◽

Mélanie Cariou ◽

Elena Vigliar ◽

Fanny Barel ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Testing ◽

Mutational Status ◽

Kappa Value ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing ◽

Control Study ◽

Mmr Proteins ◽

Good Agreement

AimWe aimed to study the prognostic value of KRAS, NRAS, BRAF mutations and microsatellite stable (MSS)/instable (MSI) in the field of colorectal cancer invading the submucosa (ie, pT1 colorectal cancer (CRC)).MethodsWe led a case-control study in tumour samples from 60 patients with pT1 CRC with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for KRAS, NRAS, BRAF mutations (Idylla testing and next generation sequencing, NGS) and MSS/MSI status (Idylla testing and expression of mismatch repair (MMR) proteins using immunohistochemistry).ResultsKRAS mutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (OR=1.11 (0.38 to 3.25), p=0.8548), NRAS mutations in 1/20 (5%) cases and 3/40 (7.5%) controls (OR=3.08 (0.62 to 15.39), p=0.1698) and BRAF mutations in 3/20 (15%) cases and 6/40 (15%) controls (OR=1.00 (0.22 to 4.5), p=1.00). A MSI status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (OR=1.2353 (0.26 to 5.79), p=0.7885). Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing KRAS, NRAS and BRAF mutations (Kappa value of 0.849 (0.748 to 0.95) between Idylla and NGS) and MSS/MSI (Idylla)—proficient MMR/deficient MMR (immunohistochemistry) status (Kappa value of 1.00).ConclusionAlthough being feasible using the fully automated Idylla method as well as NGS, the molecular testing of KRAS, NRAS, BRAF and MSS/MSI status does not seem useful for prognostic purpose in the field of pT1 CRC.

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Case Report: Effectiveness of Targeted Treatment in a Patient With Pancreatic Cancer Harboring PALB2 Germline Mutation and KRAS Somatic Mutation

Frontiers in Medicine ◽

10.3389/fmed.2021.746637 ◽

2022 ◽

Vol 8 ◽

Author(s):

Wei Wu ◽

Yu Liu ◽

Yuzhi Jin ◽

Lulu Liu ◽

Yixuan Guo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Next Generation Sequencing ◽

Somatic Mutation ◽

Germline Mutation ◽

Tissue Sample ◽

Rapid Development ◽

Parp Inhibitor ◽

Next Generation ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Pancreatic cancer is one of the most leading causes of cancer death worldwide. The rapid development of next-generation sequencing (NGS) and precision medicine promote us to seek potential targets for the treatment of pancreatic cancer. Here, we report a female pancreatic cancer patient who underwent radical surgical excision after neoadjuvant chemotherapy. After the surgery, the patient underwent gemcitabine + S-1 therapy, capecitabine + albumin paclitaxel therapy and irinotecan therapy successively, however, MRI review revealed tumor progression. The surgical tissue sample was subjected to next-generation sequencing (NGS), and PALB2 germline mutation and KRAS somatic mutation were identified. The patient then received olaparib (a PARP inhibitor) + irinotecan and the disease stabilized for one year. Due to the increased CA19-9, treatment of the patient with a combination of trametinib (a MEK inhibitor) and hydroxychloroquine resulted in stable disease (SD) with a significant decrease of CA19-9. This case demonstrated that the NGS may be a reliable method for finding potential therapeutic targets for pancreatic cancer.

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Immunohistochemistry and Next Generation Sequencing are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies

10.1101/2020.07.20.20154641 ◽

2020 ◽

Author(s):

Linyuan Wang ◽

Anna Piskorz ◽

Tjalling Bosse ◽

Mercedes Jimenez-Linan ◽

Brian Rous ◽

...

Keyword(s):

Next Generation Sequencing ◽

Endometrial Carcinoma ◽

Internal Control ◽

Molecular Subtype ◽

Serous Carcinoma ◽

Next Generation ◽

Loss Of Function ◽

Sensitivity Specificity ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next generation sequencing (NGS) in identifying PTEN abnormality. IHC and tagged-amplicon NGS PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function (LOF) PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of five PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% CI 62.7 to 85.5%), a specificity of 84.6% (95% CI 76.2 to 90.9%), and accuracy of 81.2% (95% CI 74.4 to 86.9%) in predicting LOF PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared to endometrial serous carcinoma (80.0% versus 19.4%, p<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support complementary testing of both IHC and sequencing of PTEN to assess the PTEN status in endometrial carcinomas.

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Myopericytoma of the Parotid and Molecular Profiling: Report of a Rare Case and Review of the Literature

International Journal of Surgical Pathology ◽

10.1177/10668969211070167 ◽

2021 ◽

pp. 106689692110701

Author(s):

Nicholas J. Roig ◽

Michelle Wu ◽

Osvaldo Hernandez ◽

Cheng Z. Liu ◽

Tamar C. Brandler

Keyword(s):

Rare Case ◽

Molecular Profiling ◽

Review Of The Literature ◽

Deep Lobe ◽

Positive Identification ◽

First Case ◽

Concentric Pattern ◽

Next Generation Sequencing Ngs ◽

Slow Growing ◽

Generation Sequencing

Myopericytomas are uncommon tumors defined by their round to spindle shaped cells often arranged in a concentric pattern of perivascular growth. They are typically well-circumscribed, nodular, slow-growing lesions that occur in the soft tissue of the extremities. Here, we present a 30-year-old female with a 2.4 cm myopericytoma occurring in the deep lobe of the parotid gland. The diagnosis was made with detailed histopathologic and immunohistochemical findings and positive identification of the specific mutation for PDGFRβ p.Asp666Lys by next generation sequencing (NGS). This is the first case report of a parotid myopericytoma with a genetic testing that shows a particular mutation that has been linked to myopericytomatosis.

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Chemoresistance of Gastric-Type Mucinous Carcinoma of the Uterine Cervix: A Study of the Sankai Gynecology Study Group

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001145 ◽

2018 ◽

Vol 28 (1) ◽

pp. 99-106 ◽

Cited By ~ 19

Author(s):

Atsumi Kojima ◽

Muneaki Shimada ◽

Yoshiki Mikami ◽

Shoji Nagao ◽

Nobuhiro Takeshima ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Cell Carcinoma ◽

Uterine Cervix ◽

Mucinous Carcinoma ◽

Stage Ii ◽

World Health ◽

Serous Carcinoma ◽

Endocervical Adenocarcinoma ◽

Alternative Treatment Strategy ◽

Gastric Type

ObjectiveGastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix, characterized by aggressive clinical behavior and absence of high-risk human papillomavirus. We conducted this study to evaluate the chemosensitivity of GAS compared with that of usual-type endocervical adenocarcinoma (UEA) in patients who had been enrolled in our previous study.MethodsOf 52 patients from our previous phase 2 study (SGSG005) of neoadjuvant chemotherapy with docetaxel and carboplatin for stage IB2 to IIB nonsquamous cervical cancer, 47 (stage IB2, 12; stage IIA2, 7; stage IIB, 28) were enrolled in this study with written informed consent. The biopsy specimens before neoadjuvant chemotherapy and surgical specimens after chemotherapy were centrally reviewed based on the updated World Health Organization classification (2014).ResultsOf 47 patients with nonsquamous cell carcinoma, 20 (42.6%) were diagnosed with UEA, 13 (27.7%) with GAS, 12 (25.5%) with adenosquamous carcinoma, and 1 patient each (2%) with small cell carcinoma and serous carcinoma. Consequently, 33 patients, consisting of 20 patients with UEA and 13 patients with GAS, were eligible for the current study. The response rate of GAS was significantly lower than that of UEA (46.2% vs 85.0%, P = 0.048). Of 16 cases of stage II UEA, 11 (68.8%) were downstaged on microscopic examination of postsurgical specimens, but none of the 8 patients with stage II GAS showed any response (P < 0.01). Two inoperative tumors were GAS. With a median follow-up duration of 56 months, the 5-year progression-free and overall survival rates of GAS were significantly worse than those of UEA (38.5% vs 75.0% [P = 0.011] and 36.9% vs 90.0% [P < 0.001], respectively).ConclusionsThese findings suggest that GAS should be distinguished from UEA by its chemoresistance, necessitating an alternative treatment strategy established for this distinct subtype of endocervical adenocarcinoma.

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