The fallopian tube, “precursor escape” and narrowing the knowledge gap to the origins of high-grade serous carcinoma

The distal Fallopian tube is a site of origin for many 'ovarian' high-grade serous carcinomas (HGSCs) with intraepithelial carcinomas (STICs) that share identical TP53 mutations with metastatic tumors TP53 mutation-positive early serous proliferations (ESPs) comprise a spectrum including p53 signatures and serous tubal intraepithelial lesions (STILs) and are not considered malignant; however, ESPs are often the only abnormality found in Fallopian tubes of women with metastatic HGSC The purpose of this study was to determine if a relationship exists between isolated ESPs and concurrent metastatic HGSCs in the absence of STIC Fallopian tubes from 32 HGSCs without a co-existing STIC/HGSC in the endosalpinx were exhaustively sectioned The presence of either STIC/HGSC or ESP in the endosalpinx was documented and DNA from tissues containing ESPs, concurrent HGSC, and control epithelia were interrogated for TP53 mutations by targeted amplicon-based sequencing with average coverage reads >4000 across DNA replicate samples Serial sectioning revealed a previously unrecognized STIC/HGSC in 3 of 32 (93%) and ESPs in 13 (406%) Twelve contained TP53 mutations Nine (75%) shared identical TP53 mutations with concurrent HGSCs, four at high (≥ 5%) and five at low (< 5%) allele frequency All control epithelia were TP53 mutation-negative This study, for the first time, indicates lineage identity between ESPs in the distal tube and some metastatic HGSCs via a shared site-specific TP53 mutation It supports a novel serous carcinogenic sequence in which an ESP could eventually culminate in a metastatic serous cancer via 'precursor escape' and would explain the apparent sudden onset of cancers without co-existing STICs This paradigm for serous cancer development underscores the likelihood that multiple precursor types in the Fallopian tube contribute to serous cancer development with implications for the evolution, pathologic classification, and prevention of this lethal malignancy Copyright © 2018 Pathological Society of Great Britain and Ireland Published by John Wiley & Sons, Ltd

Evidence for lineage continuity between early serous proliferations (ESPs) in the Fallopian tube and disseminated high-grade serous carcinomas

Tumors of the Cervix, Vagina, and Vulva.

Oncological surgical pathology

Practical Review of Ovarian Sex Cord-Stromal Tumors.

Declared as a pandemic by WHO on March 11, 2020, COVID-19 has brought about a dramatic change in the working of different laboratories across the country. Diagnostic laboratories testing different types of samples play a vital role in the treatment management. Irrespective of their size, each laboratory has to follow strict biosafety guidelines. Different sections of the laboratory receive samples that are variably infectious. Each sample needs to undergo a proper and well-designed processing system so that the personnel involved are not infected and also their close contacts. It takes a huge effort so as to limit the risk of exposure of the working staff during the collection, processing, reporting or dispatching of biohazard samples. Guidelines help in preventing the laboratory staff and healthcare workers from contracting the disease which has a known human to human route of transmission and high rate of mortality. A well-knit approach is the need of the hour to combat this fast spreading disease. We anticipate that the guidelines described in this article will be useful for continuing safe work practices by all the laboratories in the country.

Guidelines for various laboratory sections in view of COVID-19: Recommendations from the Indian Association of Pathologists and Microbiologists.

Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma This was a prospective case–control study carried out in a tertiary care center Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC

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Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma

Rhabdoid meningioma is a rare subtype of meningiomas accounting for 1-3% of all intracranial meningiomas and classified as WHO Grade III tumor. It has an aggressive course and needs to be treated by both surgery and radiotherapy. Here we present a rare case of rhabdoid meningioma in a 24 year old lady with complaints of focal seizures, paresis and diplopia. CT & MRI showed a mass attached to dura in left posterosuperior frontoparietal region with peripheral edema. Histopathology showed large tumor cells arranged in sheets, whorls and papillary pattern. The patient was treated by surgery followed by radiation. This is reported to aware the surgical pathologists to keep this subtype as a differential diagnosis while interpreting any meningioma as it has an aggressive course.

Rhabdoid Meningioma-An Uncommon and Aggressive Variant

Preoperative pathologic diagnosis of pelvic tumors is mandatory for proper management of patients like neoadjuvant chemotherapy and interval debulking. Currently there are many minimally invasive methods available which include fine-needle aspiration cytology (FNAC) and trucut biopsy, mostly complimentary to each other. FNAC is a cheap, rapid and sensitive method for diagnosis of pelvic tumors. It can be done as an outpatient procedure without complications. But with it, the tissue architecture cannot be seen. Trucut biopsy on the other hand reveals tissue architecture and can help in grading and subtyping of malignant tumors. Trucut biopsy has to be done under image guidance like ultrasound and computed tomography. Patient is administered local anaesthetic and can be discharged safely after 2 hours. Pathologists familiar with histomorphology can give a correct diagnosis easily. But many times sampling errors may occur; especially in large tumors, resulting only in necrosis, hemorrhage and degenerated tissue bits. Also differentiation of borderline from malignant ovarian tumors is very difficult. In case of mixed tumors one component may be missed. Hard tumors like fibromas and leiomyomas yield scanty material and result in inadequate reporting. With FNAC, the overall accuracy rate is estimated to be around 96.3%. With trucut biopsy, adequacy is from 91 to 95% and accuracy is approximately 98% in different studies. When both methods are combined, the adequacy is 100%, diagnostic accuracy 95.5%, sensitivity 94.9% and specificity 100%. Therefore depending on the clinical diagnosis and the location of tumors, either FNAC and/or trucut biopsy can be chosen.

Trucut Biopsy vs FNAC of Pelvic Tumors-Who Wins the Match?

We report here a case of carcinosarcoma arising from dermoid cyst of ovary comprising of squamous cell carcinoma and pleomorphic sarcoma with focal myogenic differentiation.A 52-year-old female presented with left lower abdominal pain and a large pelvic mass. Ultrasonography revealed a large left adnexal cystic mass with fluid level and a small solid nodule [Figure 1]. Patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The ovarian tumor was large measuring 18  12 10 cm. It was unilocular cystic mass filled with hair and yellow colored cheesy material. The thickness of cyst wall was 0.5-1.5 cm and a solid area measuring 3 cm in diameter was seen in one pole [Figure 2]. The left ovary appeared normal. The uterus was atrophic with keratinized cervix. Histopathological examination of the cyst wall showed a stratified squamous epithelial lining with focal dysplastic change and transition to infiltrating carcinoma with underlying dermal appendages. Hematoxylin and eosin stained sections from the solid area showed a malignant tumor with two distinct components. One of the components was epithelial showing diffuse squamous differentiation with extensive keratinization [Figure 3]. There was nuclear anaplasia and atypical mitosis. The other component revealed features of pleomorphic spindle cell sarcoma with marked pleomorphism and hyperchromasia, [Figure 3] frequent mitoses and necrosis. The epithelial and mesenchymal components were closely intermixed without well-demarcated boundaries. On immunohistochemistry, the malignant epithelial cells were reactive for high molecular weight keratin [Figure 4a] and P63 protein [Figure 4b] while the pleomorphic spindle cell sarcomatous component showed diffuse positivity for vimentin [Figure 4c] and focally for smooth muscle actin [Figure 4d]. Desmin, S100 protein and CD10 were negative in both components.The present case was a large ovarian cyst with characteristic squamous epithelial lining as described by Arora and Haldane who found adenocarcinoma in combination with sarcoma in dermoid cyst of ovary.

Asaranti Kar

Papers

Guidelines for various laboratory sections in view of COVID-19: Recommendations from the Indian Association of Pathologists and Microbiologists.

Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma

Rhabdoid Meningioma-An Uncommon and Aggressive Variant

Trucut Biopsy vs FNAC of Pelvic Tumors-Who Wins the Match?

Carcinosarcoma in dermoid cyst of ovary: An extremely rare malignant transformation