Metastatic Gastric Adenocarcinoma, Of Signet-Ring Type Dr. Terrence Colgan

Clinical History Peritoneal fluid. This 30 year old woman presented to the Emergency Dept. with a 4-week history of abdominal pain and a history of fullness in the upper abdomen, culminating in an increase in abdominal girth in the last few days. She had otherwise been well. A CT scan of the abdomen revealed a right ovarian mass of 12 cm, a left ovarian mass of 4 cm, massive ascites and omental thickening consistent with metastatic disease. A serum β-HCG was negative, but a serum a-fetoprotein was increased to 160 mcg/L (normal<10). A paracentesis of the abdomen was performed Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Key to diagnosis of most malignancies in malignant effusions: Can one identify a second population of foreign cells? Challenge in some cases: Is a pure population of "foreign" malignant cells present? Differential Diagnosis Adenocarcinoma Other Ovary Mesothelioma* Breast, including lobular Ca * Dysgerminoma Gastric* Lymphoma   Melanoma* *may present as single isolated cells ? Yolk Sac Tumor ? ↑'d serum a-fetoprotein Cytomorphology of Yolk Sac Tumor in Ascitic Fluid Paucity of specific features "clean background" Scattered mesothelial cells § Atypical cells in irregular & papillary groupings cell block – diagnostic features Vacuolation of Adenocarcinoma Cells Cell clusters with vacuolation Ovary and lung especially Mucin and/or degeneration (beware mesothelial cells) Isolated cells with vacuolation Gastric ca "signet ring" (Definition: Large cytoplasmic vacuolation with nuclear compression.) Lobular breast ca "bulls eye" (uncommon as initial presentation) Spieler P et al Identification of Types and Primary Sites of Malignant Tumor… Acta Cytol 1985; 5: 753. Spriggs A et al Intracellular mucous inclusions. J Clin Pathol 1975; 28: 929. How to proceed in disseminated intra-abdominal malignancy in women? Fact: Short survival, weeks/months, Alternatives: Laparotomy?, Laparoscopy? Chemotherapy? Standard therapy for ovarian carcinoma Standard therapy → Optimal cytoreductive surgery Can be achieved in at least 1/3 of patients Subsequent chemotherapy: IV platinum-taxane (6 courses) Results of standard therapy → 30% 5 year survival. Neoadjuvant therapy for ovarian carcinoma Neoadjuvant chemotherapy followed by interval debulking surgery may be an alternative for the initial management of selected (bulky) ovarian carcinoma patients EORTC-GCG 55971 & NCIC neoadjuvant chemotx vs primary debulking surgery in Stage 3C and 4 Pectasides D et al in Oncology 2005; 68: 64 – 70 Vergote I et al in Oncology 2005; 19: 1615 – 22 Now..intraperitoneal (IP) chemotherapy: ovarian carcinoma Randomized phase 3 trial of Stage 3 patients following optimal cytoreductive surgery → Superior progression-free survival and overall survival (↑'d 30% to 66 mo.) for 6 cycles of IV chemotx plus IP vs. IV chemotx alone BUT <50% could complete IP therapy Armstrong et al in NEJM 2006;354: 34-43. IP chemotherapy for ovarian carcinoma: new standard of practice? NCI (USA) supports the use of IP chemotherapy in a subset of ovarian carcinoma patients "The Society of Gynecologic Oncologists of Canada (GOC) supports the use of intraperitoneal chemotherapy in optimally debulked stage three ovarian cancer patients." – Jan. 10, 2006 http://www.nci.gov, and http://www.g-o-c.org 6 days after presentation the patient underwent laparotomy Surgeon's pre-op diagnosis → Yolk sac tumor Radiologist's description → Advanced ovarian carcinoma Pathologist's pre-op diagnosis → Adenocarcinoma, ? primary Laparotomy (1) Findings: Ascites – 7 litres Multiple peritoneal nodules throughout, including mesentery, bowel, liver, and diaphragms Omentum – multiple nodules, as well Bowel and appendix, no abnormality Omentectomy, BSO, and peritoneal biopsies were performed. Final Diagnosis & Course Diagnosis: Metastatic Gastric Adenocarcinoma, Of Signet-Ring Type At laparotomy: "indurated" & "plastered" gastric small curvature Subsequent GI endoscopy: 10 cm. length of nodular, non-ulcerated abnormality And the elevated Serum a-FP? "elevated concentrations of serum a-fetoprotein occur in most hepatocellular carcinomas and 10 – 30% of other gastrointestinal cancers" Lab Medicine Practice Guidelines of the National Academy of Clinical Biochemistry, 2006 Take home message – Case 2. Absence of a distinctive, malignant cell population in fluids can be diagnostically challenging Management options of women with ovarian carcinoma are evolving Designation of the primary site of abdominal carcinomatosis may be important Interpret radiology and biochemistry info cautiously to avoid diagnostic pitfalls. References Armstrong DK, Bundy B, Wenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. NEJM 2006; 354: 34 – 43. Foot NC. Identification of types and primary sites of metastatic tumors from exfoliated cells in serous fluids. Am J Pathol 1954; 661 – 677. Gynecologic Oncologists of Canada Statement on Intraperitoneal chemotherapy for ovarian cancer. Accessed March 21, 2006 at http://www.g-o-c.org Pectasides D, Farmakis D, Koumarianou A. The role of neoadjuvant chemotherapy in the treatment of advanced ovarian cancer. Oncology 2005; 68: 64 – 70. Epub. Ringenberg QS, Doll DC, Loy TS, Yarbro JW. Malignant ascites of unknown origin. Cancer 1989; 64: 753 – 755. Roncalli M, Gribaudi G, Simoncelli D, Servida E. Cytology of yolk-sac tumor of the ovary in ascitic fluid – report of a case. Acta Cytol 1988; 32: 113 – 116. Spieler P, Gloor F. Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Acta Cytol 1985; 5: 753 – 767. Spriggs AI, Jerrome DW. Intracellular mucous inclusions – a feature of malignant cells in effusions in the serous cavities, particularly due to carcinoma of the breast. J Clin Pathol 1975; 28: 929 – 936. Stenman U-H et al. National Academy of Clinical Biochemistry Guidelines for the Use of Tumor Markers in Testicular Cancer. Accessed April 17, 2006: http://www.nacb.org/lmpg Vergote I, van Gorp T, Amant F, Neven P, Berteloot P. Neoadjuvant chemotherapy for ovarian cancer. Oncology 2005; 19: 1615 – 1622.