How hairfall saved the patient from cancer twice – A postmenopausal patient with synchronous endometrial and endocervical carcinomas presenting with endocrine symptoms

Introduction

Menopause is a relative hyperandrogenic state but development of virilizing features like hirsutism is rather uncommon. ¹ The differential diagnosis of hyperandrogenemia includes pituitary, ovarian and adrenal sources of androgen production. ² Among the ovarian causes in postmenopausal women, ovarian virilizing tumours and hyperthecosis of the ovarian stroma are most common. ³

Stromal hyperthecosis occurs in one third of postmenopausal patients usually as an incidental finding. ⁴ The luteinized cells in this condition give rise to excess androgen production. Peripheral aromatization of androgen can lead to elevated estrogen levels, which can result in endometrial overgrowth including endometrial carcinoma. ²

Endometrial carcinoma is also seen most commonly amongst post-menopausal women, usually presenting with postmenopausal bleeding. ⁴ Another neoplasm that can present with bleeding and has similar morphology in the uterus is endocervical carcinoma which can sometimes be picked up by cervical smear screening.^4,5

Presence of synchronous endometrial and cervical cancer is quite rare, with usual association being with ovarian cancer rather than cervical. ⁶ We present a case of incidental detection of synchronous endometrial and endocervical carcinoma who presented with complaints of alopecia and hirsutism.

Case Summary

A 56-year-old postmenopausal woman presented to the Endocrinology department with complaints of alopecia and hirsutism since 7 months. She had a history of papillary thyroid carcinoma for which thyroidectomy was done 5 years back and is presently on complete remission. Hormonal assay was done which showed elevated testosterone, DHEA-S, 17 α OH progesterone and follicle-stimulating hormone (FSH).

Patient was referred to Gynaecology department for evaluation. No abnormalities were detected on pelvic ultrasound. On speculum examination, a polyp was noted measuring 2 × 1 cm which was sent for histopathology. Microscopic sections of the same showed an endometrial polyp with a focus of endometrioid carcinoma grade 1 which was further categorized by immunohistochemistry. This focus of confluent glands was positive for estrogen receptor (ER) and negative for progesterone receptor (PR), p53 showed wild type staining, and MSH6 and PMS2 showed retained staining, which conformed to a type 1 endometrial carcinoma (Figure 1).OPEN IN VIEWER

In view of diagnosis of a malignancy, magnetic resonance imaging (MRI) was done and hysterectomy was planned. MRI was largely unremarkable with mild endometrial thickening at cervical canal and plaque like enhancing area at anterior fornix which were attributed to post biopsy inflammatory changes. Hysterectomy was done which showed no growth in endometrial cavity or cervix grossly. However, on microscopy, a focus of complex compact atypical glands with focal cribriforming was noted in the cervix. Immunohistochemistry showed these neoplastic glands to be positive for p16 and carcinoembryonic antigen (CEA) and negative for ER and vimentin, and p53 showed wild type staining. Based on histopathology and immunohistochemistry, a diagnosis of endocervical adenocarcinoma was made (Figure 2).OPEN IN VIEWER

No other deposits were identified in tubes, ovaries and lymph nodes sent. Interestingly, the section from left ovary showed small clusters of luteinized stromal cells suggestive of stromal hyperthecosis (Figure 3). This was most probably the reason for her presenting symptoms. On follow-up, she reported clinical improvement in her alopecia and is doing well. Her final hysterectomy report showed endometrioid carcinoma grade 1 and endocervical carcinoma usual type, human papilloma virus (HPV) associated with Silva pattern A. Both were stage 1 disease and hence needed no adjuvant therapy.OPEN IN VIEWER

Discussion

Virilizing features of hirsutism, alopecia and acne suggest a hyperandrogenic state. Post-menopausal hyperandrogenism needs thorough investigation, as ovarian tumours leading to it are often missed on imaging and pose a risk for development of endometrial carcinoma by peripheral aromatization into estrogen. ¹ Elevated serum testosterone and normal radiology in the present case prompted a gynaecological evaluation.

Endometrial lesions due to increase in estrogen can vary from endometrial polyp, endometrial hyperplasia and endometrial adenocarcinoma. ⁷ Histopathological analysis of the polyp noted on speculum examination showed foci of endometrioid adenocarcinoma. It was confirmed by immunohistochemistry. As was the protocol, hysterectomy was done and showed a microscopic focus of usual type endocervical adenocarcinoma, and no residual lesion was noted in endometrium as it was completely restricted to the polyp that was excised. Hence, both foci of synchronous endometrioid and endocervical adenocarcinoma were of Stage IA. Grossly, no definite lesion was seen in endometrium or cervix which explained the largely unremarkable radiology.

Incidence of synchronous primary malignancies of female genital tract is about 1–6% of all genital neoplasms. ⁶ Endocervical adenocarcinoma though rare when associated with an endometrial adenocarcinoma can be difficult to identify due to overlapping morphological features. ⁵ Immunohistochemistry plays an important role in making this distinction. Endometrioid adenocarcinoma is ER/PR positive, p16 negative, CEA negative and vimentin positive. Endocervical adenocarcinoma shows an exact reverse pattern of staining to this. ⁸ Similar mutually exclusive immunohistochemical findings were noted in the two adenocarcinomas in this case.

Another distinct pathology noted in one of the ovaries which was responsible for the patient’s presenting symptoms initially is stromal hyperthecosis. Ovarian hyperthecosis is an uncommon nonneoplastic cause of hyperandrogenism, however quite common amongst postmenopausal women. Aetiology is not completely known. ²

Management of hyperthecosis is usually bilateral salpingo-oophorectomy. ³ But fortunately, on referral of the case to gynaecology, two malignancies in their early stage could be diagnosed. Considering the microscopic nature of the malignancies, no further treatment was required. Common symptoms of both these malignancies are usually abnormal uterine bleeding, yet incidentally, this patient presented with hairfall and hirsutism due to an underlying nonneoplastic ovarian pathology. After surgery, gradual clinical improvement of the symptoms was seen.

Conclusion

Combination of all three pathologies – stromal hyperthecosis, endometrial adenocarcinoma and endocervical adenocarcinoma – has not been described in literature. Fortunately, for the patient, it was the most benign condition amongst this that led to early diagnosis of the two malignancies. This emphasizes the necessity for thorough workup for even minor symptoms especially in a postmenopausal woman.