|Year : 2020 | Volume
| Issue : 2 | Page : 312-316
A rare malignancy at the gastrojejunostomy stump
Krushna Atmaram Chaudhari, Vineet Talwar, Varun Goel, Prasanta Kumar Dash, Sneha Bothra, Kshitij Domadia, Venkata Pradeep Babu Koyyala
Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
|Date of Submission||03-Jan-2020|
|Date of Decision||29-Feb-2020|
|Date of Acceptance||03-Mar-2020|
|Date of Web Publication||19-Jun-2020|
Department of Medical Oncology, Rajiv Gandhi Cancer Institute, Sector 5, Rohini, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chaudhari KA, Talwar V, Goel V, Dash PK, Bothra S, Domadia K, Babu Koyyala VP. A rare malignancy at the gastrojejunostomy stump. Cancer Res Stat Treat 2020;3:312-6
|How to cite this URL:|
Chaudhari KA, Talwar V, Goel V, Dash PK, Bothra S, Domadia K, Babu Koyyala VP. A rare malignancy at the gastrojejunostomy stump. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Jul 5];3:312-6. Available from: http://www.crstonline.com/text.asp?2020/3/2/312/287193
| Case History and Approach|| |
A 65-year old woman presented in July 2016 with a 1-month history of mild-to-moderate dull aching epigastric pain with loss of appetite. She had no history of vomiting, melena, or altered bowel habits. The patient had a history of undergoing gastrectomy and gastrojejunostomy 40 years ago for a gastric ulcer and open cholecystectomy 26 years ago for gallstone disease. Details of surgery and histopathology reports were lost and could not be recovered. Her ECOG performance status (PS) was 1, and examination was normal and with no organomegaly. Blood investigations were unremarkable except for mild anemia and hypoproteinemia.
Contrast-enhanced computed tomography (CT) of the abdomen [Figure 1] showed multiple peripherally enhancing lesions in both lobes of the liver and enlarged conglomerate lymph nodes in the periportal, peripancreatic, perigastric, precaval, preaortic, left paraaortic, and mesenteric regions. Positron-emission tomography-CT (PET-CT) showed a metabolically active gastric lesion, multiple liver space-occupying lesions (SOL), and lymph nodal disease [Figure 2]; the remaining organ systems and structures were unremarkable. Upper gastrointestinal (GI) endoscopy showed ulceration and friability at the gastrojejunostomy anastomosis likely malignant infiltration of gastrojejunostomy anastomosis [Figure 3].
|Figure 1: Computed tomography scan of abdomen axial view image showing gastric and liver lesions|
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|Figure 2: Positron emission tomography-computed tomography images showing metabolically active gastric and hepatic lesions with lymph nodal involvement|
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|Figure 3: Ulcerated and friable growth at the gastro-jejunostomy site seen on upper gastrointestinal endoscopy|
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CT-guided biopsy and fine-needle aspiration cytology and biopsy done from the liver lesion revealed poorly differentiated carcinoma. Immunohistochemistry (IHC) done was positive for cytokeratin (CK), CK7, and GATA-3 and negative for CK20, p40, PAX8, TTF-1, Hep Par1, ER, 34bE12, and mammaglobin. Breast magnetic resonance imaging (MRI) done in view of GATA-3 positivity was normal. A diagnosis of metastatic gastric adenocarcinoma was made based on the above findings. HER2/neu test was negative. The patient was started on palliative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Revaluation with PET-CT after three cycles showed progressive disease in the form of new lesions in the liver and new left deep cervical lymphadenopathy, with an increase in the size and metabolic activity of the pre-chemotherapy lesions [Figure 4]. Treatment was then changed to epirubicin-based chemotherapy (epirubicin, oxaliplatin, and capecitabine), but the patient had progressive disease on PET-CT scan after three cycles in the form of increase in the extent and metabolic activity of the liver lesions and left supraclavicular lymph nodes with appearance of new bilateral pulmonary infiltrates and persistence of the other lesions [Figure 4]. Based on the poor response to chemotherapy and poorly differentiated nature of the disease, re-biopsy from the liver SOLs was done [Figure 5].
|Figure 4: Positron emission tomography-computed tomography images showing progressive disease on palliative chemotherapy|
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|Figure 5: (a and b) Histopathology slide showing poorly differentiated carcinoma, Immunohistochemistry showing (c) diffuse cytokeratin positivity in all cells, (d) focal positivity of epithelial membrane antigen highlighting adenocarcinoma component, (e) Beta-human chorionic gonadotropin and (f) GATA-3 positivity highlighting choriocarcinoma cells|
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What is the diagnosis and what should the management plan be? Once you have finalized your answer, please turn to pg. 313 to read on.
The possible differential diagnoses considered were:
- Metastatic breast cancer in view of GATA-3 expression and beta-human chorionic gonadotropin (β-HCG) positivity on IHC; however, no breast mass was found on MRI of bilateral breasts, and other IHC markers for breast carcinoma were negative
- Metastatic ovarian choriocarcinoma in view of β-HCG positivity on IHC finding; however, bilateral adnexa and uterus were unremarkable on imaging
- Primary gastric choriocarcinoma (PGC) in view of exophytic growth at the gastric stump and β-HCG and GATA-3 positivity on IHC
- Intrahepatic cholangiocarcinoma in view of IHC findings and liver lesions
- GI stromal tumor and gastric lymphoma could be distant possibilities; however, non-corresponding histopathology and cytokeratin positivity went against these diagnoses.
| Diagnosis|| |
Histopathology showed trophoblastic differentiation. Additional IHC was positive for β-HCG [Figure 5]. Serum β-HCG level was markedly elevated at 36,902 mIU/ml. IHC with β-HCG was expressed on 40%-50% of cells; those cells were negative for epithelial membrane antigen (EMA). The diagnosis of PGC with adenomatous component was made based on histopathological evaluation and IHC. Gastric adenocarcinoma is positive for AE1/AE3 and CK7 on IHC. CK20 is usually negative; however, occasionally can be positive. The patient denied any history of previous malignancy, including gestational trophoblastic neoplasia and ovarian malignancy. Imaging of the patient was re-reviewed, and adnexal structures and uterus were normal.
The patient died of gastrointestinal bleed only a few days after the diagnosis of PGC had been established.
| Discussion|| |
Choriocarcinoma is a malignant trophoblastic neoplasm that usually manifests during pregnancy. These tumors represent <1% of gynecological malignancies. Choriocarcinoma can be gestational or nongestational. Choriocarcinoma is a β-HCG secreting tumor. β-HCG is used usually for the diagnosis, response assessment, and follow-up.
Nongestational choriocarcinoma can also be gonadal or extragonadal in origin. Extragonadal nongestational choriocarcinoma rarely develops in the mediastinum, retroperitoneum, pineal gland, liver, gallbladder, and urinary tract system. PGC was first described by Davidson in 1905. PGC is an extremely rare and highly malignant tumor; it accounts for around 0.08% of gastric cancers. The diagnosis of PGC is confirmed with high β-hCG levels in serum, choriocarcinomatous component on biopsy, and β-hCG positive cells on IHC. Ectopic production of β-HCG in the serum and its expression have been seen in various nontrophoblastic malignant tumors including pancreatic adenocarcinoma, bronchogenic carcinoma, osteosarcoma, squamous cell carcinoma, colorectal tumors, and carcinoma of the breast, ovary, prostate, kidney, parathyroid, large bowel, bladder and stomach. Gastric choriocarcinomas are red and beefy on gross appearance and show exophytic growth. On histopathology, the tumor shows malignant cytotrphoblasts and syncytiotrophoblasts, usually usually mixed with areas of typical glandular differentiation.
To date, approximately 140 cases have been reported in the medical literature. These were case reports, and the clinical, and the clinical behavior, tumor characteristics, and prognostic parameters of PGC have not been clearly described. To the best of our knowledge, a case of metastatic PGC arising from gastrojejunostomy site has not been reported before. Kobayashi et al. presented a pooled analysis of 53 cases of PGC, in which they reported that the mean age at diagnosis was 62.4 years in men and 52.8 years in women. PGC was more frequently present in the distal third of the stomach (41%). The site of origin often coincided with the site of origin of adenocarcinoma. 70% of the patients exhibited a component of adenocarcinoma in this analysis. The presence of synchronous liver metastasis, residual tumor after operation, and the absence of chemotherapy were significantly associated with a short overall survival.
Frequently, PGC is diagnosed initially as adenocarcinoma due to the coexistence of an adenomatous component, as was the case in our patient. In the pooled analysis by Kobayashi et al., only 8% of patients were correctly diagnosed with PGC on biopsy.
The etiology of PGC is poorly understood though there have been theories about its development. The most accepted hypothesis is the dedifferentiation theory from gastric adenocarcinoma which was suggested by Pick in 1926. This theory suggested that there is retrograde differentiation of adenocarcinoma cells to the embryonal ectoderm level; the cells then acquire the ability to produce trophoblasts. Points that support this hypothesis are similar age at diagnosis and location of the tumor in the stomach as compared to gastric adenocarcinoma. About 70% of PGC have an adenomatous component. PGC has been noted more frequently in the areas where gastric adenocarcinoma is more common. PGC possesses genetic characteristics of both adenocarcinoma and gestational choriocarcinoma. PGC is more prone to hematogenous spread as compared to gastric adenocarcinoma. Diagnosis of PGC requires a high index of suspicion for poorly differentiated histology, especially in patients who are unresponsive to primary chemotherapy. Re-biopsy with extensive IHC study is always encouraged in these cases.
Most of the literature regarding PGC is from case reports, and not much is known about its treatment. In the pooled analysis by Kobayashi et al., patients were treated with various chemotherapeutic regimens with single-agent or multi-agent chemotherapy regimens containing cisplatin, methotrexate, fluorouracil, mitomycin C, actinomycin D, or cyclophosphamide. Takahashi et al. have reported a case of successful treatment of gastric choriocarcinoma with curative intent with EMA/CO regimen followed by radiofrequency ablation of the lung nodule that remained after systemic therapy which led to a complete clinical response. EMA/CO is a multidrug regimen which is commonly used in high-risk gestational choriocarcinoma as the standard of care. It consists of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (Oncovin).
| Conclusion|| |
PGC is an extremely rare, highly malignant tumor with poor prognosis. This is the first reported case of metastatic PGC arising from the gastrojejunostomy site. In the case of a poorly responsive gastric tumor, re-biopsy and extensive IHC are encouraged. Optimal treatment for PGC at present is not known, and further evaluation and research are needed in this field.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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