Journal of Mid-life Health Journal of Mid-life Health
Home | About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions | Online submission | Subscribe | Advertise Users Online: 297  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size 

 Table of Contents 
Year : 2022  |  Volume : 13  |  Issue : 3  |  Page : 247-250  

Leydig cell hyperplasia of ovary – An unusual finding in postneoadjuvant chemotherapy case of primary fallopian tube carcinoma

1 Department of Pathology and Lab Medicine, AIIMS, Jodhpur, Rajasthan, India
2 Department of Surgical Oncology, AIIMS, Jodhpur, Rajasthan, India

Date of Submission28-Jun-2022
Date of Decision12-Jul-2022
Date of Acceptance03-Aug-2022
Date of Web Publication14-Jan-2023

Correspondence Address:
Meenakshi Rao
Department of Pathology, AIIMS, Jodhpur, Rajasthan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmh.jmh_117_22

Rights and Permissions

A large number of high-grade serous ovarian carcinomas originate in the fallopian tubes. Neoadjuvant chemotherapy followed by surgery may lead to a number of chemotherapy-induced changes in the ovary, which may lead to an erroneous diagnosis. We present a rare case of a 55-year-old postmenopausal woman who was clinically diagnosed with carcinoma of the right ovary; on histopathologic evaluation after neoadjuvant chemotherapy, the primary site was found to be the right fallopian tube. The right ovary showed chemotherapy-related changes along with extensive Leydig cell hyperplasia. As the presence of Leydig cell hyperplasia in this setting is an unusual finding, it may pose a diagnostic dilemma for the pathologist; so an awareness of this entity is important to avoid misdiagnosis.

Keywords: Leydig cell hyperplasia, primary fallopian tube carcinoma, Neoadjuvant chemotherapy

How to cite this article:
Chaturvedi K, Rao M, Saha S, Vishnoi JR, Nalwa A. Leydig cell hyperplasia of ovary – An unusual finding in postneoadjuvant chemotherapy case of primary fallopian tube carcinoma. J Mid-life Health 2022;13:247-50

How to cite this URL:
Chaturvedi K, Rao M, Saha S, Vishnoi JR, Nalwa A. Leydig cell hyperplasia of ovary – An unusual finding in postneoadjuvant chemotherapy case of primary fallopian tube carcinoma. J Mid-life Health [serial online] 2022 [cited 2023 Jan 26];13:247-50. Available from:

   Introduction Top

The incidence of primary fallopian tube carcinoma is rising, advancements in molecular and genetic studies have shown that a large number of cases which were earlier considered being ovarian or peritoneal in origin had their primary lesion in the fallopian tubes.[1] Although the site of origin of high-grade serous carcinomas of the ovary is an ongoing topic of debate, many studies have suggested serous tubal intraepithelial carcinoma (STIC) as a potential primary site. It is a noninvasive lesion usually found in the distal epithelium of the fallopian tube.[2] According to CAP (college of American pathologists) cancer protocol, in presence of STIC, the primary site of ovarian high-grade serous carcinoma is assigned as the fallopian tube.[3]

Conventional treatment of advanced ovarian carcinomas was surgery followed by chemotherapy. Platinum-based neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS) was recommended by the National Comprehensive Cancer Network guidelines, 2012. This approach was found to reduce morbidity and improve survival time.[4] For pathologists, this approach brought the challenging task of recognizing postchemotherapy effects in patients with high-grade serous carcinomas of the ovary.

It is vital for the histopathologist to be aware of the postchemotherapy changes that can be expected in the ovary, so that one may not misdiagnose them as residual cancer or a concurrent pathology. Some known changes are nucleomegaly, clumping of chromatin, hyperchromasia, bizarre nuclei, cytoplasmic vacuolization, etc. Furthermore, changes may be seen in stroma such as fibrosis, necrosis, inflammation, and dystrophic calcification including the presence of psammoma bodies.[5]

Here, we present a rare case of primary fallopian tube serous carcinoma, which was clinically diagnosed with ovarian carcinoma; with post-NACT changes along with Leydig cell hyperplasia. We present this case to raise awareness that Leydig cell hyperplasia of the ovary may be seen in a case of postchemotherapy primary fallopian tube carcinoma.

   Case Report Top

A 55-year- old postmenopausal woman presented with abdominal pain and distention of the abdomen for 2 months. There were no complaints of nausea, vomiting, altered bladder, bowel habits, vaginal discharge, decreased appetite, or weight loss. She has two children and no history of sterilization or Oral contraceptive pills (OCP) intake or hormonal treatment. A computed tomography scan showed an enlarged heterogeneous right ovary with omental deposits. Following this, she underwent an ascitic tap and her CA 125 level was found to be 241.9 U/ml. She was diagnosed with ovarian carcinoma in August 2019. Following which she was given four cycles of NACT with paclitaxel and carboplatin between August to October 2019, after which her CA 125 level dropped to 15.79 U/mL. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy in January 2020.

Grossly right ovary measured 2.5 cm × 1 cm × 1 cm and was adhered to the posterior surface of the uterus. Cut surface showed few whitish areas. The right fallopian tube was grossly unremarkable. The omentum showed no deposits on gross examination. On histomorphologic evaluation, the primary site was identified as the right fallopian tube which showed features of STIC which was confirmed with p53 immunohistochemistry (IHC) [Figure 1]. The fimbrial end of the right fallopian tube and right ovary showed residual cancer in the form of an invasive tumor composed of solid nests, acini, trabeculae, and cords of moderately pleomorphic cells [Figure 2]. The cells contain moderate amounts of eosinophilic cytoplasm and hyperchromatic nuclei with 0–1 nucleoli. Endometrium had a benign endometrial polyp along with intramural and subserosal leiomyomas. Omentum was free from tumor deposits and chemotherapy response score (CRS)3.
Figure 1: Section of the fallopian tube with serous tubal intraepithelial carcinoma (left H and E) highlighted by p53 antibody (right)

Click here to view
Figure 2: Sections from the fallopian tube (left) and ovary (right) showing evidence of residual carcinoma (H and E)

Click here to view

The right ovary also showed evidence of postchemotherapy changes including necrosis, hyalinization, collagenization, hemorrhage, few hemosiderin-laden macrophages, and psammoma bodies. Furthermore, there were variable-sized multiple clusters of Leydig cells [Figure 3] in the ovarian stroma, and there was no atypia or significant mitosis observed in Leydig cell clusters. IHC stain for calretinin was performed on formalin-fixed paraffin-embedded tissue for confirming the diagnosis of Leydig cell hyperplasia [Figure 4].
Figure 3: Section from the ovary showing Leydig cell hyperplasia (H and E)

Click here to view
Figure 4: Section from the ovary showing Leydig cell hyperplasia highlighted by calretinin

Click here to view

Although this patient was not tested for testosterone levels either before or after chemotherapy, this patient had no known symptoms of virilization or any other relevant history that would suggest the presence of Leydig cell hyperplasia in a patient before chemotherapy. Hence, we postulate this finding as a chemotherapy-related change.

In February 2022, the patient developed massive ascites and multiple liver metastases, consistent with progressive disease.

   Discussion Top

Neoadjuvant chemotherapy is a comparatively newer treatment modality for ovarian carcinomas and not many studies have been done on the chemotherapy-related histomorphological changes. Although there are various studies done on NACT changes in other organs such as the breast, colon, etc., not much literature is available on post-NACT changes in ovarian or fallopian tube carcinomas. This leaves room for making an erroneous diagnosis.

Reijnen et al.[6] quantified Leydig cells and stromal hyperplasia in the ovary of postmenopausal patients with endometrial carcinoma. They compared Leydig cell number in endometrioid-type of endometrial carcinoma (EEC) against that in non-EEC (NEEC), using ovaries of patients with benign gynecological diseases as control. This quantification led to the observation that means Leydig cell numbers in EEC cases were much higher (282.8) when compared to NEEC cases (76.3) and 66.4 in controls. They concluded that Leydig cells may contribute to the development of EEC by increased androgen production in postmenopausal women. In our patient, however, Leydig cell hyperplasia was observed in a post-NACT serous carcinoma of the fallopian tube with a high-grade serous carcinoma ovary and no associated malignancy of the endometrium.

Analysis of morphological changes in specimens of IDS, after NACT in 67 patients of epithelial ovarian carcinomas was done by Samrao et al.[4] using four criteria – inflammation, fibrosis, necrosis, and residual tumor. They recognized stromal fibrosis as the most significant prognosis predicting factor in cases of epithelial ovarian carcinoma.

Tiwana et al.[5] studied post-NACT changes in patients of ovarian carcinoma; they used five morphological parameters and graded them – inflammation, fibrosis, necrosis, psammoma bodies, and residual tumor; inflammation was scored as mild (1+) and extensive (2+); fibrosis was scored as mild (1+), moderate (2+), and severe (3+); necrosis was scored as absent (0), 1%–50% (1+) and present >50% (2+). Psammoma bodies were scored as absent (0) and present (1+); residual tumor <5% (1+), 5%–50% (2+), and >50% (3+). They observed extensive inflammation, 1+ necrosis, and moderate fibrosis as the most common findings. Our case had all of the above mentioned five features along with Leydig cell hyperplasia.

McCluggage et al.[7] considered the absence of residual tumor and presence of psammoma bodies as a good response to chemotherapy. Our patient showed the presence of psammoma bodies; however, she also had a residual tumor and later showed evidence of disease progression with metastasis to the liver.

   Conclusion Top

Leydig cell hyperplasia of the ovary is a very unusual feature in the setting of primary fallopian tube carcinoma after neoadjuvant chemotherapy. The pathologist needs to be aware of this entity, as postchemotherapy residual carcinoma may be scant to absent and the presence of Leydig cell hyperplasia may be misdiagnosed as germ cell tumor or sex cord-stromal tumor or as poorly differentiated carcinoma.

We would also like to emphasize the importance of providing a detailed history of the patient, especially related to chemotherapy. It helps in correctly assessing chemotherapy-related changes and avoiding misdiagnosing them as residual carcinoma. It is also required for the assessment of CRS and pathologic staging (pTNM, American Joint Committee on Cancer AJCC).

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Rexhepi M, Trajkovska E, Ismaili H, Besimi F, Rufati N. Primary fallopian tube carcinoma: A case report and literature review. Open Access Maced J Med Sci 2017;5:344-8.  Back to cited text no. 1
Kim J, Park EY, Kim O, Schilder JM, Coffey DM, Cho CH, et al. Cell origins of high-grade serous ovarian cancer. Cancers (Basel) 2018;10:433.  Back to cited text no. 2
Protocol for the Examination of Specimens from Patients with Primary Tumors of the Ovary, Fallopian Tube, or Peritoneum. Available from: [Last accessed on 2022 Jun 26].  Back to cited text no. 3
Samrao D, Wang D, Ough F, Lin YG, Liu S, Menesses T, et al. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy. Transl Oncol 2012;5:469-74.  Back to cited text no. 4
Tiwana KK, Nibhoria S, Kaur M, Monga T, Gupta R. Postchemotherapy histopathological evaluation of ovarian carcinoma: A 40-case study. Chemother Res Pract 2015;2015:197871.  Back to cited text no. 5
Reijnen C, Küsters-Vandevelde HV, Abbink K, Zusterzeel PL, van Herwaarden AE, van der Laak JA, et al. Quantification of Leydig cells and stromal hyperplasia in the postmenopausal ovary of women with endometrial carcinoma. Hum Pathol 2019;85:119-27.  Back to cited text no. 6
McCluggage WG, Lyness RW, Atkinson RJ, Dobbs SP, Harley I, McClelland HR, et al. Morphological effects of chemotherapy on ovarian carcinoma. J Clin Pathol 2002;55:27-31.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded12    
    Comments [Add]    

Recommend this journal