Goblet Cell Adenocarcinoma of Appendix with Ovarian Metastasis: A Case Report

1. Postgraduate Student, Department of Pathology, Sri Ramachandra Institute of Medical Science and Research, Chennai, Tamil Nadu, India. 2. Associate Professor, Department of Pathology, Sri Ramachandra Institute of Medical Science and Research, Chennai, Tamil Nadu, India. 3. Senior Resident, Department of Pathology, Sri Ramachandra Institute of Medical Science and Research, Chennai, Tamil Nadu, India. 4. Senior Consultant, Department of Surgical Oncology, Sri Ramachandra Institute of Medical Science and Research, Chennai, Tamil Nadu, India.

Abstract

Goblet Cell Adenocarcinoma (GCA) is a rare neoplasm of the appendix composed of goblet like mucinous cells, classified as adenocarcinoma. High-grade GCA of appendix with large aggregates of mucin containing goblet shaped cells, secondarily involving the ovary with signet ring cells is very rare. Such cases pose a significant diagnostic challenge, as the pelvic mass may clinically mimic as a primary ovarian malignancy, thereby delaying identification of the true appendiceal origin. This is a case of 50-year-old postmenopausal female who presented with complaints of significant weight loss (5 kg) since one month and recurrent vomiting since one month. Clinical examination revealed a large pelvic mass. Ultrasonography of abdomen and pelvis revealed malignant neoplasm in pelvis with involvement of uterine stump and vagina. Biopsy of the pelvic mass showed malignancy, however, the primary site remained inconclusive, necessitating further workup to exclude a gastrointestinal/gynaecological primary. The patient underwent surgical exploration. Histopathological examination of appendix demonstrated tumour cells arranged in anastomosing trabeculae, irregular nests, glands and cords with singled out goblet-shaped mucin-secreting cells and areas of high-grade transformation showing signet ring cell morphology. Histopathological examination of ovarian mass showed mucin filled signet ring cells. Individual tumour cells showed abundant intracytoplasmic (cellular) mucin with basally displaced, mildly to moderately pleomorphic nuclei. Immunohistochemistry showed positivity for CK20, CDX2, SATB2, CK19, synaptophysin; CK7 and PAX8 were negative, confirming primary appendiceal origin. This immunophenotype excludes primary ovarian mucinous carcinoma and confirms ovarian metastasis consistent with Krukenberg tumour. This case highlights the diagnostic pitfall of misinterpreting appendiceal GCA as a primary ovarian malignancy when the patient presents with a pelvic mass. High-grade transformation with signet ring cell features carries a poor prognosis requiring immediate management. This case is unique because of a grossly normal-appearing appendix despite underlying malignancy, presenting as a primary ovarian mass. The diagnostic difficulty due to high-grade transformation with signet ring cell morphology highlights the need for broad spectrum immunohistochemistry panel before labelling a pelvic mass as primary ovarian in origin.

Appendix neoplasm, Grossly normal appendix, Histopathology, Immunohistochemistry, Mucinous cells, Ovarian mass

Case Report

A 50-year-old postmenopausal woman presented with progressive abdominal pain, recurrent vomiting and significant weight loss (5 kg) for one month. There was past history of hysterectomy done for fibroids in 2014. On examination, she was cachectic with mild pallor. Abdominal examination revealed a large, firm pelvic mass arising from the left-side with ascites. Laboratory parameters showed elevated Cancer Antigen 125 (CA125)-78 U/mL (<35 U/mL) and Carcinoembryonic Antigen (CEA)-4.72 ng/mL (<3 ng/mL). Ultrasonography of abdomen and pelvis revealed malignant neoplasm in pelvis with involvement of uterine stump and vagina. Contrast-enhanced PET-CT showed a large hypermetabolic left adnexal mass (142×94×144 mm) with moderate ascites, peritoneal deposits and left external iliac lymph node involvement, suggestive of advanced ovarian malignancy (Table/Fig 1). A Computed Tomography-guided biopsy from the pelvic mass revealed tumour cells arranged in anastomosing trabeculae, nests, cords, and glands with intracellular mucin. The patient underwent cytoreductive surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Intraoperatively, extensive peritoneal deposits and large left adnexal mass were noted. Appendix was removed due to thickened tip which arose suspicion. Grossly, the cut surface of pelvic mass with attached vault, bilateral fallopian tubes and left ovary showed a well circumscribed lesion measuring 15×14×8 cm which was firm in consistency. Right ovary couldn’t be visualised separately. Histopathological examination of ovarian mass showed mucin filled signet ring cells. Individual tumour cells showed abundant intracytoplasmic (cellular) mucin with basally displaced, mildly to

moderately pleomorphic nuclei (Table/Fig 2), (Table/Fig 3). Grossly, the received appendix measured 5 cm in length and 0.6 cm in external diameter. The serosal surface appeared smooth and unremarkable. On cut section, the wall thickness was approximately 0.2 cm. The lumen was patent and the mucosa appeared unremarkable with no obvious lesion. Histopathological examination of appendix showed goblet shaped mucin containing cells. The tumour cells were arranged in anastomosing trabeculae, irregular nests, microglands, tubules and single cells, with intracytoplasmic (cellular) mucin and peripherally pushed nuclei (Table/Fig 4), (Table/Fig 5). Lymphovascular and perineural invasion were present (Table/Fig 6). The tumour was infiltrating the appendiceal wall, submucosa, muscularis propria and the serosa. Multiple peritoneal deposits were also identified. The important in this case included primary ovarian mucinous carcinoma, metastatic colorectal adenocarcinoma, signet ring cell carcinoma and appendiceal mucinous adenocarcinoma. Primary ovarian tumours are usually CK7 and PAX8 positive, whereas in this case tumour cells were CK20, CDX2 and SATB2 positive with CK7 and PAX8 negativity, favouring a gastrointestinal origin. Though metastatic colorectal carcinoma can show a similar immunoprofile, no colorectal lesion was identified clinically or radiologically and the morphology showed goblet-like cells with intracellular mucin, supporting GCA. Pure signet ring cell carcinoma typically shows diffuse poorly cohesive cells without the characteristic goblet cell clustering seen here. Appendiceal mucinous adenocarcinoma usually shows abundant extracellular pools of mucin. This case showed predominantly intracellular mucin within tumour cells. The combined histomorphological features and immunohistochemistry CK7-, CK20+, CK19,PAX8-, SATB2+) (Table/Fig 7), (Table/Fig 8), (Table/Fig 9), (Table/Fig 10), (Table/Fig 11) with patchy synaptophysin positivity (Table/Fig 12) favoured GCA. Two of thirty lymph nodes examined showed metastasis. Based on American Joint Committee on Cancer (AJCC) 8th edition, diagnosis was given as pT4 pN1b pM1c, GCA of appendix, high-grade with signet ring cell features with ovarian and peritoneal metastasis. M1c was assigned due to ovarian metastasis (Krukenberg) and peritoneal metastasis. For prognosis, immunohistochemistry for Microsatellite instability (MLH1, MSH2, MSH6, PMS2) were done which showed intact nuclear expression (Mismatch Repair (MMR)- proficient) and Programmed Death-Ligand 1 (PD-L1) was negative. The patient has completed three cycles of chemotherapy and is on regular 16
follow-up with serial imaging and tumour markers, considering the high-risk of recurrence.

Discussion

The GCA is a rare primary epithelial tumour of the appendix characterised by mucinous features with variable neuroendocrine differentiation. According to the WHO 5_th edition, it is placed under adenocarcinomas due to its infiltrative growth pattern and aggressive clinical behaviour (2). The most common presentation of GCA is acute appendicitis, particularly in low-grade and localised disease, whereas high-grade or metastatic tumours often present with non specific abdominal pain, with or without an abdominal mass (3). Fukasawa H et al., in their study, reported that ovarian metastasis may favour in appendiceal GCA and may mimic primary ovarian mucinous neoplasms. He described in his study about a middle-aged female who presented with elevated serum CEA and an ovarian mass, later identified as metastatic GCA of appendiceal origin, highlighting the diagnostic challenge in differentiating primary ovarian tumours from metastatic lesions (4). Carr NJ et al., mentioned that due to non specific clinical and radiological features, these tumours are frequently misdiagnosed preoperatively (5). In the present case, the patient presented with a pelvic mass suspicious for ovarian malignancy, similar to previously reported cases. However, unlike the commonly described bilateral ovarian involvement, the disease in this case appeared more localised, contributing to diagnostic difficulty. Histologically, GCA demonstrates a spectrum ranging from well-formed goblet cell clusters to poorly differentiated adenocarcinoma. Tang LH et al., proposed a classification dividing these tumours into typical (Group-A), signet ring cell type (Group-B), and poorly differentiated adenocarcinoma (Group-C), with higher grades correlating with more aggressive behaviour and worse prognosis (6). The present case showed high-grade morphology with signet ring–like cells and infiltrative growth, corresponding to Group-B/Group-C tumours. In contrast, low-grade tumours remain localised with a relatively favourable outcome. Peritoneal dissemination is the most common route of spread in GCA and influences prognosis. Sugarbaker PH highlighted that transcoelomic spread with peritoneal involvement plays a major role in disease progression in appendiceal neoplasms (7). Ovarian metastasis is thought to occur through this pathway and is often associated with peritoneal disease. The presence of peritoneal involvement in the present case is in keeping with previously reported advanced stage disease. Immunohistochemistry is essential for differentiating metastatic GCA from primary ovarian tumours. Dragomir A et al., demonstrated that SATB2 is a useful marker for tumours of colorectal and appendiceal origin (8). Bell PD and Pai RK described the typical immunoprofile of GCA, which includes CK20 and CDX2 positivity with variable CK7 expression, supporting a lower gastrointestinal origin (9). The present case demonstrated a similar immunophenotype. Soltani H et al., described in his study that GCA shows focal positivity for neuroendocrine markers such as synaptophysin (69%) but lacks specificity (10). Prognosis in GCA is largely determined by tumour grade and stage. High-grade tumours with metastatic disease have poorer outcomes compared to low-grade lesions (6). The present case, with high-grade histological features and metastatic spread, is comparable to previously reported aggressive cases and indicates an unfavourable prognosis. Overall, this case shares several features with previously published reports, including high-grade morphology, ovarian metastasis and peritoneal dissemination. However, the relatively localised ovarian involvement at presentation and grossly normal appendix highlights the variability in clinical presentation and emphasises the importance of considering an appendiceal primary in patients presenting with ovarian masses.

Conclusion

The GCA of the appendix is a rare but clinically significant tumour with aggressive behaviour and a tendency for metastasis, particularly
to the ovaries. This case highlights the importance of considering an appendiceal primary in patients presenting with ovarian mass. Careful histopathological evaluation, supported by immunohistochemistry is essential for accurate diagnosis. Early recognition is crucial, as it directly influences management and prognosis.

DOI and Others

DOI: 10.7860/JCDR/2026/91302.24368

Date of Submission: Jun 23, 2026
Date of Peer Review: Jul 28, 2026
Date of Acceptance: Aug 11, 2026
Date of Publishing: Sep 01, 2026

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 08, 2026
• Manual Googling: Aug 06, 2026
• iThenticate Software: Aug 08, 2026 (1%)

ETYMOLOGY: Author Origin

EMENDATIONS: 6