Submitted by: Emily Goebel, MD FRCPC and Helen Ettler, MBChB, FRCPC

A Very Rare Ovarian Tumour

Clinical History

• 78 year old female

• Chief Complaint: pelvic pain - 6 month history of:

• worsening abdominal pain• urinary urgency and difficulty voiding• early satiety• night sweats• 15 lbs weight loss

• Past Surgical History: • Hysterectomy for benign disease• Partial bowel resection for diverticulitis• Cholecystectomy

Pelvic computed tomography

• 9 cm irregular, necrotic mass in right hemi-pelvis with attachment to the pelvic sidewall and involving:

• vaginal vault• colon at the site of previous colorectal anastomosis• ileal bowel loop with possible fistulization

• Right hydronephrosis

• Retroperitoneal lymphadenopathy

• 1.3 cm liver lesion, favour metastasis

Macroscopic Examination

• Patient underwent partial right oophorectomy for diagnosis

• Gross examination:• Multiple fragments of tan tissue (5.5 x 5 x 3 cm in aggregate) with a focal

cystic area (0.6 cm). No residual ovarian parenchyma identified.

Low power view of solid and necrotic ovarian tumour• Diffuse nests of tumour cells with large areas of necrosis

Small cells with round to ovoid hyperchromatic nuclei, nuclear molding, stippled chromatin and scant cytoplasm

Areas with microcystic architecture

Areas of overt epithelial differentiation - Endometrioid and squamous differentiation

Pan Cytokeratin

CD56

Immunohistochemistry

Positive Negative

Pan Cytokeratin – strong in squamous and glandular areas, weak in small cell carcinoma

PAX-8

Neuroendocrine markers: diffuse CD56 and synaptophysin, focal chromogranin

ER

p40 and p63 (very focal) WT-1

TTF-1

CD10

Final Diagnosis

Ovarian small cell carcinoma, pulmonary type

Definition

• Small cell carcinoma arising in the ovary and resembling small cell carcinoma of lung origin

• Also called: Neuroendocrine carcinoma, small cell type; Small cell carcinoma, pulmonary type

Epidemiology

• Rare malignancy

• Occurs in post-menopausal women• Mean age 59 years (range 28-85)

Clinical Presentation

• Symptoms related to pelvic or abdominal mass• Pain

• Increased abdominal girth

• Bloating

• Early satiety

• Urinary frequency

• Change in bowel habits

Macroscopic Features

• Large, tan-yellow or gray-white solid tumour • Mean size: 13.5 cm (range 4.5 – 26 cm)

• Frequent areas of necrosis

• Often bilateral ovarian masses with extra-ovarian spread

Microscopic Features

• Resembles pulmonary small cell carcinoma

• Cells are small with hyperchromatic nuclei and scant cytoplasm

• “Salt and pepper” chromatin

• Nuclear molding

• Surface epithelial tumour component is commonly present (ex. endometrioid, mucinous, squamous differentiation)

• Abundant necrosis

• Can arise in association with mature cystic teratoma or other epithelial tumour (ex. mucinous carcinoma) (case reports)

Immunohistochemistry

• Variably positive for neuroendocrine markers:• Synaptophysin• Chromogranin• CD56

• Cytokeratin can be focally positive, especially if there is a surface epithelial tumour component

• Variable TTF-1• TTF-1 positivity does not indicate metastasis from lung

Differential Diagnosis

Neuroendocrine Carcinoma

Primary Ovarian

Small cell carcinoma,

Pulmonary type

Large cell Neuroendocrine

Carcinoma

Metastasis (ex. Small cell

carcinoma of lung )

Undifferentiated Tumour

Small cell carcinoma,

Hypercalcemic type

Differential DiagnosisSmall cell carcinoma, hypercalcemic type - Younger age (2nd-3rd decade)

- Paraneoplastic syndrome = hypercalcemia- Diffuse sheets of cells with focal follicle like spaces- Monotonous, hyperchromatic nuclei with clumped

chromatin and nucleoli- Immunohistochemistry: Diffuse WT-1 positivity,

focal EMA, cytokeratin, CD10, and calretinin positivity

- SMARCA4 loss

Metastatic small cell carcinoma (ex. Lung primary) - Clinical history- No admixed ovarian surface epithelial tumour

component

Large cell neuroendocrine carcinoma - Larger cells with abundant cytoplasm, larger nuclei and prominent nucleoli

Ovarian Small Cell Carcinoma

Pulmonary type Hypercalcemic type

Follicle-like spacesSolid nested and microcystic pattern

Ovarian Small Cell Carcinoma

Pulmonary type Hypercalcemic type

Pleomorphic small cells with hyperchromatic nuclei, stippled chromatin, and scant cytoplasm

Monotonous small cells with round nuclei, vesicular chromatin, small nucleoli and scant cytoplasm

Prognosis

• Poor prognosis

• Aggressive tumour

• Extra-ovarian spread and metastasis are common

• Usually presents at high stage

Treatment

• Management is multidisciplinary and should be discussed at tumour boards

• Due to rarity, there is no consensus on optimal treatment

• Limited mostly to case reports

• Surgical resection and tumour debulking• Hysterectomy and bilateral salpingo-oophorectomy• Retroperitoneal and pelvic lymphadenectomy• Cytoreductive surgery

• Adjuvant chemotherapy (Reed NS (2014). Int J Gynecol Cancer)

• Multi-drug chemotherapy• Platinum drug and etoposide (similar to small cell carcinoma of lung) (Tsolakidis D. (2012). Eur J Gynaecol Oncol.)

• Regimen similar to ovarian epithelial tumours: carboplatin and paclitaxel (Kursaki A. (2013). Int J Gynecol Pathol. and Suzuki N 2007). J Obstet Gynaecol Res.)

• Radiation therapy has been used for residual pelvic disease in some cases

References

1. Eichhorn JH, Young RH, Scully RE. Primary ovarian small cell carcinoma of pulmonary type. A clinicopathologic, immunohistologic, and flow cytometric analysis of 11 cases. Am J Surg Pathol. 1992 Oct;16(10):926-38.

2. Fukunaga M, Endo Y, Miyazawa Y, Ushigome S. Small cell neuroendocrine carcinoma of the ovary. Virchows Arch. 1997 Apr;430(4):343-8.3. Grandjean M, Legrand L, Waterkeyn M, Baurain JF, Jadoul P, Donnez J, Marbaix E. Small cell carcinoma of pulmonary type inside a microinvasive mucinous

cystadenocarcinoma of the ovary: a case report. Int J Gynecol Pathol. 2007 Oct;26(4):426-31.4. Ikota H, Kaneko K, Takahashi S, Kawarai M, Tanaka Y, Yokoo H, Nakazato Y. Malignant transformation of ovarian mature cystic teratoma with a predominant pulmonary type

small cell carcinoma component. Pathol Int. 2012 Apr;62(4):276-80.5. Kurasaki A, Sakurai N, Yamamoto Y, Taoka H, Takahashi K, Kubushiro K. Ovarian pulmonary-type small cell carcinoma: case report and review of the literature. Int J Gynecol

Pathol. 2013 Sep;32(5):464-70.6. Lim SC, Choi SJ, Suh CH. A case of small cell carcinoma arising in a mature cystic teratoma of the ovary. Pathol Int. 1998 Oct;48(10):834-9. 7. Suzuki N, Kameyama K, Hirao T, Susumu N, Mukai M, Aoki D. A case of pulmonary type of ovarian small cell carcinoma. J Obstet Gynaecol Res. 2007 Apr;33(2):203-6.8. Reed NS, Pautier P, Åvall-Lundqvist E, Choi CH, du Bois A, Friedlander M, Fyles A, Kichenadasse G, Provencher DM, Ray-Coquard I. Gynecologic Cancer InterGroup (GCIG)

consensus review for ovarian small cell cancers. Int J Gynecol Cancer. 2014 Nov;24(9 Suppl 3):S30-4. 9. Tsolakidis D, Papanikolaou A, Ktenidis K, Pervana S. Primary ovarian small cell carcinoma of pulmonary type with enlarged paraaortic lymph node masses: a case report and

review of the literature. Eur J Gynaecol Oncol. 2012;33(3):312-5. 10. Yin L, Li J, Wei Y, Ma D, Sun Y, Sun Y. Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving

tamoxifen: A case report and literature review. Medicine (Baltimore). 2018;97(23):e10900.11. WHO Classification of Tumours Editorial Board. Female genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [cited 2021 March].

(WHO classification of tumours series, 5th ed.; vol. 4). Available from: https://tumourclassification.iarc.who.int/chapters/34.12. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours of Female Reproductive Organs. Lyon (France): International Agency for Research on Cancer

(IARC); 2014. (4th ed.)