a case of ?primary neuroendocrine tumor of ovary

1. TUMOUR CLINICUNIT I13-09-2011

2. Mrs. R 53 years old multiparous post menopausal lady with complaints of Lower abdominal pain since 7-8months Loose stools since 7-8 months

3. h/o lower abdominal pain/ discomfort off and on intermittent, : 7-8 months with no aggravating or relieving factors with radiation to the back h/o passage of loose stools, 7-8 episodes per day : 7-8 months Relieved with conservative management

4. H/o perception of vague abdominal mass since the last 2 months H/o off and on headache present : 2 months H/o decreased appetite and weight loss ( says lost around 10-15 kg in the past six months) No h/o any fever/cough/ hemoptysis No h/o melaena or hematochezia No h/o any altered bladder habits

5. Menstrual h/o: Post-menopausal since 8yrs Peri-menopausal transition was smooth Previous cycles: 3-4d/28-30d with avg. flow. No h/o dysmenorrhoea No h/o of any post menopausal bleeding

6. PAST H/o : k/c/o Hypothyroidism since 4-5 yrs On ELTROXIN 125µgms OD FAMILY H/o: NS OBSTETRIC H/o: P2022 P1 (29yrs) NVD A & H P2 (25years) NVD A & H P3 MTP for unwanted pregnancy P4 MTP for unwanted pregnancy

7. Was being investigated at private clinic TTG Negative Stool for occult blood : Negative Stool for routine microscopy : Normal RFT- 23/0.8 LFT – 14/30/82 Sr. B12 : 60 Sr. Ca+2 : 8.5 PTI 91% CA 125 = 132 IU

8. Chest X Ray : mild Cardiomegaly USG(7/4/11) : Large complex cystic mass in pelvis with minimal ascites Ovarian mass13.5 X 8.5 cm with thick internal septae with few internal echoes Both ovaries not seperately visualized Min. free fluid seen Aorta and IVC normal

9. CECT WHOLE ABDOMEN(15/4/11): A large solid cystic, soft tissue mass lesion seen in pelvis and lower abdomen measuring 14.4 X 6.4 X 9.5cm. The solid component is moderately enhancing and is seen on the left lateral part of the lesion. No obvious calcification seen. Fat planes with uterus and right lower ureter are lost with right hydroureteronephrosis. It is abutting urinary bladder left ureter, sigmoid colon, and few of small bowel loops.

10. There is a 5.8 X 2.9 X 2.8 cm sized nodular soft tissue mass in mesentry in right lower abdomen with spiculated margins. Nodular thickening and stranding of omentum also seen Liver enlarged with multiple hypo dense lesions seen in the left lobe(at least 3) and in the right lobe( 2 in number) largest measuring 2.7 X 2.0cm in size. GB not visualized (post- cholecystectomy status) Pancreas spleen and urinary bladder normal IVC and Aorta appear normal

11. No e/o any significant periportal/ mesenteric /retroperitoneal/pelvic lymphadenopathy. No free fluid in peritoneal cavity No pleural effusion. No obvious nodules in visualized lower lung

12. On examination Afebrile Pulse 92/min BP - 120/80mm of Hg No pallor/edema/cyanosis/clubbing/lymphadenopathy Breast & thyroid – normal Chest clear P/A examination: a solid irregular ill defined mass of around size of 16 weeks gravid uterus felt in the pelvis and lower abdomen with restricted mobility.

13. Per speculum: Cervix taken up Greenish discharge present : vaginitis Pap taken Per vaginam: Uterus bulky and could not be felt seperately from the mass Through the left fornix solid firm irregular mass of 13 X 14cm With restricted mobility, ill defined margins and non tender Per rectally: same irregular mass was felt

14. Clinical impression Clinical impression : 53 years old post menopausal lady with hypothyroidism with malignant adnexal mass (ovarian) with metastases(liver)

15. Blood group: B Positive Hb 9.4gm/dl TLC – 8800/cu mm Platelets – 4.6lacs RFTs – 38/1.1 PTI - 97% FBS = 96mg% HIV - NR HBsAg – NR Urine c/s – sterile ECG - normal

16. CA 125 – 132 IU/ml CA 19.9 – 1.0 Mammography- normal Upper GI Endoscopy : normal Colonoscopy : extrinsic compression of sigmoid colon

17. Planned for NACT i/v/o liver metastases FNAC (ultrasound guided) of the right adnexal mass was done: A-2829/11: malignant tumour- cellular mild pleomorphism, s/o possibly malignant epithelial ovarian tumor However, possibility of sertoli cell tumour cannot be ruled out.

18. Taken up for staging laparotomy with TAH with BSO INTRA-OP: Midline vertical incision extended supra - umbilically Abdomen opened Ascites was present- fluid was taken for peritoneal cytology 18 X 12cm mass seen arising from the left ovary Adhesions present between the sigmoid colon and the tumor mass were separated.

19. Breach in the serosa of sigmoid colon was sutured TAH with BSO was done Right tube and ovary were normal Pelvic peritoneum was indurated Omental cake present – infracolic omentectomy done Residual disease : omental Small 1cm deposits over left cardinal ligament Peritoneum Abdomen closed in layers

20. Parts of urine output was blood tinged. Intra op cystoscopy done- b/l ureteric orifice seen urine reflux seen. 1 unit blood transfusion was given intra-op.

21. Post-operative period Monitored satisfactorily 1 unit blood was given post op Intake/output was maintained On I.V Ciplox / Metrogyl Had a fever spike on day 3 and had wound soakage complaints of multiple episodes of loose stools(15-20 times) Had developed hypokalemia – k+ correction given Stool sent for c/s- no e/o Cl. Difficiles( adv b GE Cx) negative Started on inj. Neurobion forte IM OD X 5days(i/v/o dlow Sr. vit B12)

22. PERITONEAL CYTOLOGY(2092/11): No malignant cells seen HISTOPATHOLOGY: GROSS: MICROSCOPICALLY: tumour arranged in the form of solid nests, islands and focally in tubules with fine fibro vascular septa. Tumour cell are mildly pleomorphic with fine granular chromatin and moderate amount of granular eosinophilic cytoplasm.

23. DIAGNOSIS Left ovary – Neuroendocrine carcinoma Right ovary – metastasis present Uterus, cervix and B/L fallopian tubes – free of tumour Omentum – tumour deposits FINAL DIAGNOSIS : STAGE IIIB

24. DISCUSSION Neuroendocrine tumors of ovary

25. CARCINOMA OF THE OVARY: STAGINGCLASSIFICATION USING THE FIGO NOMENCLATURE I Growth limited to the ovaries Ia Growth limited to one ovary; no ascites present containing malignant cells; no tumor on the external surfaces; capsule intact Ib Growth limited to both ovaries; no ascites present containing malignant cells; no tumor on the external surfaces; capsules intact Ic* Tumor stage Ia or stage Ib but with tumor on the surface of one or both ovaries; Or with capsule ruptured; Or with ascites present containing malignant cells or with positive peritoneal washings

26. II Growth involving one or both ovaries with pelvic extension IIa Extension and/or metastases to the uterus and/or tubes IIb Extension to other pelvic tissues IIc* Tumor stage IIa or stage IIb but with tumor on the surface of one or both ovaries; Or with capsule(s) ruptured; Or with ascites present containing malignant cells Or with positive peritoneal washings

27. III Tumor involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes; superficial liver metastasis equals stage III; tumor is limited to the true pelvis but with histologically verified malignant extension to small bowel or omentum IIIa Tumor grossly limited to the true pelvis with negative nodes with histologically confirmed microscopic seeding of abdominal peritoneal surfaces IIIb Tumor of one or both ovaries; histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes negative IIIc Abdominal implants 2 cm in diameter and/or positive retroperitoneal or inguinal nodes

28. IV Growth involving one or both ovaries with distant metastasis; if pleural effusion is present, there must be positive cytological test results to allot a case to stage IV; parenchymal liver metastasis equals stage IV

29. Carcinoid/ Neuroendocrine tumors Classified under Germ cell neoplasms of 0vary which comprise of Germ cell tumors Dysgerminoma Endodermal sinus tumor Embryonal carcinoma Polyembryoma Choriocarcinomas

31. Mixed forms (tumors composed of types A–F in any possible combination)

32. Carcinoid of the ovary Primary Carcinoid tumors of ovary account for less than 5% of all Carcinoid tumors. And for less than 0.1% of all ovarian neoplasms. Are typically localized (89%) Nearly all primary ovarian neoplasms are unilateral

33. The tumours are typically classified as germ cell tumors of the ovary and can be divided into four categories: Insular Trabecular Mucinous Mixed

34. Primary Carcinoid tumors typically behave in a benign fashion. Most ovarian carcinoids contain the insular pattern, are unilateral and early stage. It is important to establish that these are not metastatic carcinoids. Insular followed by trabecular are the most common subtypes that metastasize to ovary.

35. Given the rarity of the disease, it is also critical to rule out a metastatic GI Primary that could have metastasized to ovary and tend to present as bilateral ovarian metastases. The constipation and hirsutism are thought to be due to the release of peptide YY(PYY) by the tumors.

36. The majority of women with primary ovarian Carcinoid tumours are found incidentally on cross sectional or ultrasound imaging. Rarely, they may also present with abdominal pain, constipation, hirsutism, and a pelvic

37. For women who present with a stage I primary ovarian carcinoid, the prognosis is excellent, with greater than 90% survival. Women with more advanced diseased, the prognosis poor. (Octreotide has been used in some reports)

39. INSULAR CARCINOID: Most common type of ovarian carcinoid. Occurring in patients with between 40 & 80 years of age. Majority present with a pelvic mass and approximately 40% will have clinical evidence of carcinoid syndrome. Those presenting with carcinoid syndrome have larger masses(>7cm). It is important to differentiate a primary lesion from a ovarian metastases.

40. Typically slow growing. For those limited to the ovary, the 10 yr survival 100%(if unilateral) With advanced stage disease, the 5-year survival is 33%.

41. TRABECULAR CARCINOID: Second most common In women 30 – 70 years of age. Not typically associated with carcinoid syndrome, but may be associated with constipation due to PYY. No reported tumor related deaths

42. MUCINOUS CARCINOID: Rare Occur in patients between 30 and 80years of age Tumors may be pure or may be associated with mature cystic teratomas. One need to consider that the ovarian tumor may be a metastasis from gastrointestinal tumor. In mucinous carcinoid, an appendicectomy should be performed to exclude the more common primary mucinous appendiceal carcinoid. Overall survival good

43. Management The most recent Neuroendocrine tumor NCCN guidelines recommend that the tumor be removed completely with the goal of attaining negative margins. If the diagnosis is known or suspected pre-operatively, Octreotide (100-500mcgSQ/IV every 6 – 12h) be administered immediately prior to or during resection to avoid carcinoid crisis. In ovarian carcinoid tumors, fertility sparing surgery is permissible as these tumors are generally unilateral and associated with a good prognosis. But can include radical debulking surgery dependent on patients age and disease distribution.

44. Most common metastatic sites include regional lymph node, liver, bone and lung. Most demonstrate a remarkable tropism for the liver. Liver lesions should be considered for resection to control tumor burden and NCCN guidelines recommend that those lesions that are not resectable should be considered for cryotherapy, radiofrequency ablation, or regional embolisation.

45. Role of adjuvant therapy No evidence to support the use of either hormonal, chemotherapy or radiation therapy for gynecological carcinoid tumours.

46. Advanced stage or Recurrent disease