Publications by authors named "Nairi Tchrakian"

14 Publications

  • Page 1 of 1

Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique.

Int J Gynecol Cancer 2022 Aug 1;32(8):977-985. Epub 2022 Aug 1.

Division of Gynecologic Pathology, University of Leipzig, Leipzig, Germany.

Objectives: Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.

Methods: In this retrospective cohort study, 68 cases treated by vulvar field resection were identified from the Leipzig School of Radical Pelvic Surgery. Immunohistochemistry for p16 and p53 was performed at three different institutions and evaluated independently by seven pathologists and two trainees. Tumors were classified into one of four groups: HPV associated, HPV independent p53 wild type, HPV independent p53 abnormal, and indeterminate. Selected cases were further interrogated by (HPV RNA in situ hybridization, sequencing).

Results: Final subclassification yielded 22 (32.4%) HPV associated, 41 (60.3%) HPV independent p53 abnormal, and 5 (7.3%) HPV independent p53 wild type tumors. Interobserver agreement (overall Fleiss' kappa statistic) for the four category classification was 0.74. No statistically significant differences in clinical outcomes between HPV associated and HPV independent vulvar squamous cell carcinoma were observed.

Conclusion: Interobserver reproducibility of vulvar squamous cell carcinoma subclassification based on p16 and p53 immunohistochemistry may support routine use in clinical practice. Vulvar field resection surgery showed no significant difference in clinical outcomes when stratified based on HPV status.
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http://dx.doi.org/10.1136/ijgc-2021-003251DOI Listing
August 2022

Cutaneous Myoepithelial Neoplasms on Acral Sites Show Distinctive and Reproducible Histopathologic and Immunohistochemical Features.

Am J Surg Pathol 2022 Mar 31. Epub 2022 Mar 31.

Department of Pathology and Laboratory Medicine.

Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.
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http://dx.doi.org/10.1097/PAS.0000000000001896DOI Listing
March 2022

Placenta increta mimicking placental site trophoblastic tumor.

Int J Gynecol Cancer 2021 11;31(11):1481-1485

Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada

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http://dx.doi.org/10.1136/ijgc-2021-002988DOI Listing
November 2021

Can variant negative be high-grade serous ovarian carcinoma? A case series.

Gynecol Oncol Rep 2021 May 12;36:100729. Epub 2021 Feb 12.

Division of Medical Oncology & Hematology, Bras Family Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1Z5, Canada.

• variant negative high-grade serous ovarian cancer is rare and can still show p53 abnormal immunohistochemistry.•Diagnostic and therapeutic considerations include pathologic, molecular and clinical domains.•Genetic reassessment through more comprehensive assays should be considered to ensure no missed rare or complex variants.•Presence of mutations can occur in variant high-grade serous ovarian cancer.
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http://dx.doi.org/10.1016/j.gore.2021.100729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910505PMC
May 2021

Concise Reporting of Benign Endometrial Biopsies is an Acceptable Alternative to Descriptive Reporting.

Int J Gynecol Pathol 2022 Jan;41(1):20-27

In the United Kingdom, endometrial biopsy reports traditionally consist of a morphologic description followed by a conclusion. Recently published consensus guidelines for reporting benign endometrial biopsies advocate the use of standardized terminology. In this project we aimed to assess the acceptability and benefits of this simplified "diagnosis only" format for reporting non-neoplastic endometrial biopsies. Two consultants reported consecutive endometrial biopsies using 1 of 3 possible formats: (i) diagnosis only, (ii) diagnosis plus an accompanying comment, and (iii) the traditional descriptive format. Service users were asked to provide feedback on this approach via an anonymized online survey. The reproducibility of this system was assessed on a set of 53 endometrial biopsies among consultants and senior histopathology trainees. Of 370 consecutive benign endometrial biopsies, 245 (66%) were reported as diagnosis only, 101 (27%) as diagnosis plus a brief comment, and 24 (7%) as diagnosis following a morphologic description. Of the 43 survey respondents (28 gynecologists, 11 pathologists, and 4 clinical nurse specialists), 40 (93%) preferred a diagnosis only, with 3 (7%) being against/uncertain about a diagnosis only report. Among 3 histopathology consultants and 4 senior trainees there was majority agreement on the reporting format in 53/53 (100%) and 52/53 (98%) biopsies. In summary, we found that reporting benign specimens within standardized, well-understood diagnostic categories is an acceptable alternative to traditional descriptive reporting, with the latter reserved for the minority of cases that do not fit into specific categories. This revised approach has the potential to improve reporting uniformity and reproducibility.
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http://dx.doi.org/10.1097/PGP.0000000000000761DOI Listing
January 2022

Recurrent angina from spontaneous left atrial dissection.

Eur Heart J Cardiovasc Imaging 2021 Jul;22(8):e135

Royal Berkshire NHS Foundation Trust, London Road, Reading, UK.

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http://dx.doi.org/10.1093/ehjci/jeab024DOI Listing
July 2021

Pneumothorax and Pneumatocoele Formation in a Patient with COVID-19: a Case Report.

SN Compr Clin Med 2021 7;3(1):269-272. Epub 2021 Jan 7.

Department of Pathology, The Royal London Hospital,, Barts Health NHS Trust, London, UK.

Coronavirus disease 2019 (COVID-19) causes significant morbidity and mortality for a proportion of infected patients, and our knowledge and understanding of its clinical, radiological and histopathological features are still evolving. An association between COVID-19 and pneumothorax has been described in an increasing number of case reports and series in the literature, which have largely focused on clinical and imaging features. We report the case of a patient who developed COVID-19 complicated by pneumothorax, requiring surgical intervention. We describe the histopathological features seen in the thorascopically resected bullectomy specimen-this is, to our knowledge, the first reported description of the morphological features of pneumothorax in this important clinical setting.
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http://dx.doi.org/10.1007/s42399-020-00689-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788383PMC
January 2021

COVID-19 and pneumothorax: a multicentre retrospective case series.

Eur Respir J 2020 Nov 19;56(5). Epub 2020 Nov 19.

Royal Papworth Hospital, Cambridge, UK.

Introduction: Pneumothorax and pneumomediastinum have both been noted to complicate cases of coronavirus disease 2019 (COVID-19) requiring hospital admission. We report the largest case series yet described of patients with both these pathologies (including nonventilated patients).

Methods: Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival.

Results: 71 patients from 16 centres were included in the study, of whom 60 had pneumothoraces (six with pneumomediastinum in addition) and 11 had pneumomediastinum alone. Two of these patients had two distinct episodes of pneumothorax, occurring bilaterally in sequential fashion, bringing the total number of pneumothoraces included to 62. Clinical scenarios included patients who had presented to hospital with pneumothorax, patients who had developed pneumothorax or pneumomediastinum during their inpatient admission with COVID-19 and patients who developed their complication while intubated and ventilated, either with or without concurrent extracorporeal membrane oxygenation. Survival at 28 days was not significantly different following pneumothorax (63.1±6.5%) or isolated pneumomediastinum (53.0±18.7%; p=0.854). The incidence of pneumothorax was higher in males. 28-day survival was not different between the sexes (males 62.5±7.7% females 68.4±10.7%; p=0.619). Patients aged ≥70 years had a significantly lower 28-day survival than younger individuals (≥70 years 41.7±13.5% survival <70 years 70.9±6.8% survival; p=0.018 log-rank).

Conclusion: These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and we encourage continuation of active treatment where clinically possible.
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http://dx.doi.org/10.1183/13993003.02697-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487269PMC
November 2020

Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses' health study and health professionals follow-up study.

Int J Cancer 2017 12 20;141(12):2471-2479. Epub 2017 Sep 20.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55-1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32-0.79) in patients with intense CASR expression (p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64-1.13) and 0.81 (0.58-1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression.
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http://dx.doi.org/10.1002/ijc.31021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768412PMC
December 2017

Phyllodes tumour of the urinary bladder: a report of a unique case.

Histopathology 2018 01 24;72(2):356-358. Epub 2017 Oct 24.

Department of Histopathology, Tallaght Hospital, Dublin, Ireland.

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http://dx.doi.org/10.1111/his.13344DOI Listing
January 2018

Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

J Clin Endocrinol Metab 2016 06 26;101(6):2520-7. Epub 2016 Apr 26.

Departments of Epidemiology (T.U.A., K.M.W., E.N., H.D.S., E.G., L.A.M., I.M.S.) and Department of Nutrition (E.G.), Harvard T. H. Chan School of Public Health, Department of Medical Oncology (R.L., M.L.), Dana-Farber Cancer Institute, Divisions of Preventive Medicine (H.D.S.), and Channing Division of Network Medicine (K.M.W., E.G., L.A.M.), Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115; Department of Histopathology Research (N.T., S.F.), Trinity College, Dublin 8, Ireland; and Public Health Sciences Division (I.M.S.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.

Context: Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression.

Objective: We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer.

Design: A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer.

Setting: The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study.

Participants: We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009.

Main Outcome: Participants were followed up or cancer-specific mortality or development of metastatic disease.

Results: On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0).

Conclusions: Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.
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http://dx.doi.org/10.1210/jc.2016-1082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891799PMC
June 2016

Suspected ovarian molar pregnancy after assisted reproductive technology conception: a diagnostic challenge.

BMJ Case Rep 2015 Apr 2;2015. Epub 2015 Apr 2.

Royal College of Surgeons, Ireland.

A 32-year-old patient with primary infertility received in vitro fertilisation (IVF) therapy. Four weeks later she developed intermittent left iliac fossa pain. Transvaginal ultrasound showed an empty uterus and an adnexal mass adjacent to the right ovary. Serum β-human chronic gonadotropin was 33,492 IU/L. At laparoscopy a mass attached to right ovary, suggestive of a right ovarian ectopic pregnancy, was excised. Histological examination confirmed an ovarian ectopic gestation, but noted enlarged chorionic villi and trophoblastic atypia, which raised the suspicion of molar pregnancy. Subsequent p57 immunohistochemistry and DNA ploidy studies excluded a mole, however. Cases of suspected molar disease in ectopic pregnancy present a diagnostic challenge for both clinicians and histopathologists, and establishing a definitive diagnosis may be difficult.
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http://dx.doi.org/10.1136/bcr-2015-209353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401974PMC
April 2015

Eosinophilic ascites with marked peripheral eosinophilia: a diagnostic challenge.

Eur J Gastroenterol Hepatol 2014 Apr;26(4):478-84

aDepartment of Surgery, Trinity Centre, St James's Hospital and Trinity College bDepartment of Pathology cDepartment of Immunology dDepartment of Gastroenterology, St James's Hospital, Dublin, Ireland.

Eosinophilic disease of the gastrointestinal tract is rare and is characterized by the presence of gastrointestinal symptoms in association with eosinophilic infiltration of any part of the gastrointestinal tract. Clinical presentation of eosinophilic gastroenteritis (EGE) varies not only by the part of the gastrointestinal tract involved but also with the depth of eosinophilic infiltration of the gut wall. We describe the case of a 41-year-old woman with a history of atopy who presented with severe abdominal pain and diarrhoea. Investigations showed large-volume eosinophil-rich ascites and a markedly elevated peripheral blood eosinophil count and immunoglobulin E level. Bone marrow aspirate, trephine biopsy and T-cell studies showed no evidence of underlying haematological malignancy. Vasculitic disease and parasitic infection were systematically excluded. Colonic and upper gastrointestinal biopsies confirmed a diagnosis of EGE with eosinophilic ascites. The patient was treated with systemic corticosteroids and dietary allergen elimination with dramatic therapeutic response. The diagnostic and therapeutic challenges associated with EGE in its various forms are discussed.
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http://dx.doi.org/10.1097/MEG.0000000000000037DOI Listing
April 2014
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