Uncommon Manifestations of Endocervical Malignant Mixed Mullerian Tumor with Incidental Bilateral Fallopian Tube Carcinoma

INTRODUCTION

Malignant mixed Mullerian tumors (MMMTs) are metaplastic carcinomas including both sarcomatous and carcinomatous elements commonly involving the uterus and ovary. ^[1,2] MMMTs constitute less than 5% of the uterine malignancies, rarely involving the endocervical region. Recent studies have provided evidence to classify them as variants of carcinoma. ^[2] Primary adenocarcinoma of the fallopian tube is a rare tumor, accounting for only 0.3-1% of all gynecological malignancies. ^[3] Bilateral involvements are still rare. The diagnosis is seldom made pre-operatively because the signs and symptoms are not specific and are often mistaken for ovarian tumor or tubo ovarian mass. ^[3,4] Some tubal primaries with disseminated disease involving the ovaries are misclassified as ovarian in origin. ^[3,5] We are reporting an extremely rare case of endocervical MMMT, leiomyoma uterus and bilateral fallopian tube carcinoma in a perimenopausal woman.

CASE REPORT

A 43-year-old gravida 2, para 2, non-tubectomised perimenopausal female presented with bleeding per vagina (PV) and lower abdominal pain since 1 month. Bleeding PV was continuous, with no clots. Lower abdominal pain was of the spasmodic type, mainly in the supra pubic region. She had intermenstrual bleeding since 6 months. The patient had last child birth 23 years ago by caesarian section. General and systemic examinations were unremarkable. Per-speculum examination revealed a polyp protruding through the external os measuring 2cm × 1cm × 1cm, which was expelled spontaneously. Her hemogram, biochemical parameters, X-ray chest, ultrasound of abdomen and pelvis were within normal limits. Human immunodeficiency virus, hepatitis B surface antigen and hepatitis C virus tests were negative. The computed tomography abdomen and pelvis revealed a small soft tissue density lesion in the anterior uterocervical junction measuring 2cm × 1cm. The endometrial cavity was normal and no ascites or lymph nodes were detected. Hysteroscopy revealed a growth within the lateral wall of the uterus. Curettings from endometrial and endocervical region were collected for examination. Based on histopathology report of expelled polyp and curettings, extended hysterectomy with bilateral salphingo oophorectomy was performed. Intraoperatively, the uterus was 8 weeks in size. Both the fallopian tubes showed hydrosalphynx. Both the ovaries were normal. No free fluid was seen in the peritoneal cavity.

Pathological Findings

The spontaneously expelled grey-brown polyp [Figure 1a] on microscopy showed biphasic tumor cells with the epithelial component arranged in papillary structures and tubules. The stromal component [Figure 1b] showed oval to spindle tumor cells within a myxoid background and numerous proliferating vascular channels. Also, areas of hemorrhage and necrosis were seen. Features were suggestive of MMMT. Curettings from the endometrium and endocervix tissue [Figure 2a] showed papillary carcinoma-endocervix.

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Figure 1:

(a) The endocervical epithelium and stroma showing malignant features (hematoxylin and eosin, ×100), (b) Deeper stroma showing endometrial stromal sarcoma features (hematoxylin and eosin, ×400)

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Figure 2:

(a) Curettage material with papillary carcinoma (hematoxylin and eosin, ×100), (b) Cut surface of the hysterectomy specimen with friable tissue in the endocervical region

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The extended hysterectomy specimen showed tiny friable material in the endocervical region [Figure 2b] and intramural leiomyoma, 1cm × 0.5cm in the posterior wall of the uterus. The left fallopian tube was tortuous and dilated, 4cm × 2cm × 1cm. The right fallopian tube was enlarged and tortuous, 5cm × 2cm × 2cm, with a solid grey white to yellowish appearance on the cut surface. Microscopy showed a proliferative endometrium. The endocervix showed minute papillary carcinomatous tissue tethered to the surface. The myometrium showed tiny intramural leiomyoma. The left fallopian tube showed in situ papillary carcinoma [Figure 3a]. The right fallopian tube showed invasive serous papillary carcinoma with in situ changes in the adjoining tubal epithelium [Figure 3b]. Both ovaries were normal. In view of the histological findings in the expelled polyp, curettage material and with the hysterectomy findings, a final diagnosis of MMMT-endocervix, intramural leiomyoma and bilateral primary fallopian tube carcinoma was made.

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Figure 3:

(a) Left fallopian tube carcinoma with in situ carcinoma (hematoxylin and eosin, ×100) (b) Right fallopian tube carcinoma with invasive carcinoma (hematoxylin and eosin, ×400)

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DISCUSSION

This collision tumor of MMMT-endocervix, leiomyoma uterus and bilateral fallopian tube carcinoma is an extremely rare entity. Such a combination of manifestations could not be found on extensive review of the literature. The tubal carcinoma may occur as a part of multiple upper genital tract malignancies. ^[6]

The MMMT accounts for <5% of the uterine corpus neoplasms and, rarely, involves the endocervical region. ^[1,2,7,8] They are similar to uterine lesions, commonly presenting as post-menopausal bleeding. They present with enlarged irregular uterus and tumor protruding through the cervical os as a polypoidal mass. ^[2] Our patient was a perimenopausal lady with pervaginal bleeding, lower abdominal pain and with friable polyp protruding through the external os.

MMMTs on histology show an admixture of malignant epithelial and mesenchymal elements. The epithelial element may be endometrioid, serous, clear cell, mucinous, squamous and undifferentiated carcinoma. The stroma may be homologous in the form of endometrial stromal sarcoma, fibrosarcoma and leiomyosarcoma or heterologous like rhabdomyosarcoma and chondrosarcoma. ^[1,2,7,8] In our case, the epithelial component was of a serous type and homologous stroma showed endometrial stromal sarcoma. The MMMTs metastasize to the pelvic and para aortic lymph nodes, pelvic soft tissues, vagina and peritoneal surfaces of the upper abdomen. Surgical stage is the most important prognostic factor in MMMT. Small MMMTs confined to the tip of a polyp can have a favorable prognosis; such tumors can metastasize and be fatal. ^[2] In our case, pelvic organs, peritoneal surfaces and the pelvic and para aortic lymph nodes were free. Primary adenocarcinoma of the fallopian tube was first described by Renand in 1897, and is the rarest malignancy of the female genital tract. ^[3] These tumors occur between 14 and 88 years of age, with the majority in the 6 ^th -7 ^th decades. ^[3,5] Vaideeshwar et al.^[9] described tubal carcinoma in a 40-year-old female, which was comparable to our case. The duration of symptoms in such patients ranges from 3 days to a few years.

Patients with abdominal pain seek medical attention earlier than those with vaginal discharge or menstrual problems. ^[6] However, in our case, the patient had abdominal pain and menstrual problems.

Primary tubal carcinoma is rarely found in the in situ stage. ^[6] In our case, left fallopian tube carcinoma was in an in situ stage while right tube carcinoma was invasive. Sarangetham et al. reported bilateral tube carcinoma associated with leiomyoma. ^[3] Hydrops tubae profluens is the typical finding of primary fallopian tube carcinoma in magnetic resonance imaging. ^[4,6] Pre-operative and imaging studies show findings similar to fallopian tube carcinoma in hydrosalphynx, tubo-ovarian abscess and ovarian neoplasm, making its diagnosis difficult. ^[4] This could explain why its diagnosis was missed in our case on imaging and pre-operatively.

Diagnosis of fallopian tube carcinoma is based on the following two criteria: ^[10] (a) main tumor mass to be confined to the tube with demonstrable carcinoma in situ changes in the adjacent mucosa and (b) uterus and ovaries should be normal. In our case, bilateral fallopian tubal carcinoma was confined to the lumen of both the tubes, with in situ changes in the adjacent tubal mucosa. The ovary and endometrial tissue were normal. However, MMMT was seen within the endocervix.

The tumor stage has a better prognostic value than the histological grade in fallopian tube malignancies. Serous papillary tubal carcinomas may be associated with marked chronic inflammation. Various forms of salphingitis, including tuberculosis, may produce severe hyperplasia of the tubal epithelium with sufficient reactive atypia and mitotic activity to mimic in situ or invasive adenocarcinoma. Close attention to severe nuclear atypia and abnormal mitosis and evidence of invasion is always necessary to prevent misdiagnosis. ^[3]

Serum CA 125 is reported to be elevated in fallopian tube carcinoma, and its pre-treatment level is considered to be an independent prognostic factor. ^[3] In our case, bilateral fallopian tube carcinoma was an incidental finding and, hence, the serum CA 125 level was not assessed. However, its post-operative level was within normal limits.

Post-operatively, the patient received five cycles of chemotherapy (carboplatin 600 mg). After 1 year of therapy, she remained asymptomatic and is still under regular follow-up.