Localized gastric mesothelioma with nodal metastasis—an exceptionally rare entity

Abstract

Localized mesothelioma is a rare disease with very few reports of presentation in visceral organs. We report a case of localized gastric mesothelioma with lymph node metastasis in a 32-year-old man without asbestos exposure. A failed attempt at resection was made before presentation at another center. He was given perioperative chemotherapy that was followed by a D2 radical subtotal gastrectomy and hyperthermic intraperitoneal chemotherapy. Histopathology showed epithelioid mesothelioma with nodal metastasis but without visceral peritoneal involvement. Cytoreductive surgery and regional chemotherapy are standard in diffuse mesothelioma. Management of localized mesothelioma is anecdotal; however aggressive surgery plays a central role with selective use of perioperative chemotherapy.

Introduction

Mesothelioma is a rare malignancy with asbestos exposure being the only known environmental risk factor. Pleura is the most common site followed by peritoneum in 10–15% of all cases [1]. The link with asbestos is weaker for peritoneal disease with 30–50% of cases having exposure compared to 80% in pleural disease[2]. Overall, this disease has a dismal prognosis without treatment. Standard treatment involves surgery to achieve complete resection with regional and systemic chemotherapy as indicated. Majority of peritoneal mesotheliomas are of the diffuse variety and are rare in its localized forms. The case reported is of a localized gastric mesothelioma with nodal metastasis without conclusive proof of visceral or parietal peritoneal disease that was treated with perioperative chemotherapy, surgery, and HIPEC.

Case description

A 32-year-old man with no comorbidities was evaluated for upper abdominal pain of 2 months duration at another center. Physical examination was unremarkable. A contrast enhanced computerized tomography (CT) showed a 5 × 4 cm growth from the posterior wall of the stomach. Endoscopy found an extrinsic bulge without mucosal involvement. Serum levels of CEA and CA19-9 were normal (1.73 ng/ml and 2.26U/ml, respectively). Laparotomy was performed where they found the mass to be adherent to the pancreas, and after a partial excision, the surgery was abandoned. He then presented to our hospital a month later. Review of pathology showed epithelioid mesothelioma with immunohistochemistry staining positive for WT-1 and Calretinin. There was no history suggestive of asbestos exposure in the past. Fresh CT showed residual mass of 4.5 × 2.6 cm near the antral region with multiple enlarged regional nodes, largest measuring 1.7 cm (Fig. 1a). He was given 3 cycles of neoadjuvant chemotherapy with pemetrexed and cisplatin. There was partial response of the nodes with stable disease on the stomach wall (Fig. 1b). He was explored with the plan for cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Intraoperatively, there were extensive adhesions from previous exploration. Extra-bursal plane was dissected and the pancreas was found to be uninvolved. There was a 5-cm mass infiltrating the posterior wall of the antrum with enlarged perigastric nodes without any evidence of peritoneal disease. Subtotal gastrectomy, omentectomy, and D2 lymphadenectomy were performed (Fig. 2). HIPEC was then delivered via the open technique using cisplatin (50 mg/m²) and Adriamycin (15 mg/m²) for 90 min at 41.5⁰C. Reconstruction was done with Roux en Y gastrojejunostomy after completion of HIPEC. He had an uneventful postoperative recovery.

Fig. 1.

a Prechemotherapy CT showing growth in the posterior wall of stomach (green arrows) with Enlarged perigastric and Left Gastric Nodes (white arrow). b Post-chemotherapy CT showing stable growth in the stomach (yellow arrow) and reduction in size of metastatic nodes (black arrow)

Fig. 2.

a Resected Specimen seen from posterior side. b Resection bed

On gross examination, the mucosa was uninvolved (Fig. 3a) and a whitish firm tumor was appreciated on incising the mucosa (Fig. 3b). Microscopically the muscularis was infiltrated by residual viable epithelioid mesothelioma. Subserosal fat was involved while the serosa was free of disease. Tumor was composed of cells of epithelioid morphology arranged in tubulopapillary and glandular pattern. The tumor cells were polygonal with abundant eosinophilic cytoplasm, vesicular round nuclei, and small nucleoli. Background was composed of a fibrotic stroma with interspersed inflammatory cells. Necrosis was not seen. On immunohistochemical analysis, the tumor cells were positive for mesothelial markers like WT1 (nuclear), mesothelin (cytoplasmic and membranous), calretinin (cytoplasmic), and CK7 (membranous) (Fig. 4). They were negative for CK20, CDX2, CEA, and TTF1. Of the 17 nodes dissected, 5 had metastatic deposits. All margins were free of tumor. Adjuvant chemotherapy with pemetrexed and cisplatin was given for 3 cycles, and the patient is disease-free at 30 months of follow-up.

Fig. 3.

a Specimen divided along greater curvature showing intact mucosa over the tumor. b Firm white gritty tumor seen on incision of the mucosa

Fig. 4.

Immunohistochemical analysis: (a) CK7 (10x), (b) mesothelin (10x), (c) calretinin (10x), and (d) WT1 (10x)

Discussion

Large majority of mesotheliomas are of diffuse variety, while localized forms are extremely rare occurring at an unknown incidence. Prognosis is better for localized disease with a possibility of cure, while survival is dismal for its diffuse forms. Survival ranges from 6 to 12 months in untreated individuals extended by aggressive surgery and regional chemotherapy to 34–90 months [3].

In the case presented, it is unsure if the tumor arose from the gastric serosa or its musculature. It is natural to assume that the serosal lining is the cell of origin for mesothelioma, but the lack of invasion beyond the serosa into the retro-gastric tissues and the lack of multiplicity of deposits stand to argue against it. Involvement of subserosal fat and muscularis may favor the gastric muscles as the site of origin. Since there was no invasion beyond the subserosa, the adherence to pancreatic capsule could likely be due to previous surgery. There are very few reports in literature where there was no evidence of visceral peritoneal involvement in localized mesotheliomas arising from solid and tubular organs. You et al. reported on a localized gastric mesothelioma in a 6-year old where the serosa was uninvolved [4], and this is the only other reported case of isolated gastric mesothelioma. Isolated case reports of visceral mesothelioma were described by various authors in the esophagus, pancreas, liver, spleen, and the mesentery [5–9]. In contrast to localized peritoneal mesotheliomas, there is greater abundance in descriptions of localized pleural mesotheliomas. To the best of literature search, our case appears to be the only report of localized gastric mesothelioma in an adult. To add to the rarity, the involvement of lymph nodes is uncommon in mesothelioma, especially so in its localized forms. Takehara reported a case of localized mesothelioma of the transverse colon with nodal metastasis [5]. The patient did not receive any chemotherapy and recurred in 7 months and succumbed to the disease in 18 months. For diffuse peritoneal disease, lymph node metastasis occurs in 7–13% of cases with survivals significantly worse of those with metastasis [6].

Management of localized mesothelioma is extrapolated from diffuse peritoneal mesothelioma where cytoreductive surgery and regional chemotherapy are the standard of care [7]. None of the above-mentioned authors that treated localized peritoneal mesotheliomas have used regional chemotherapy. All of them were primarily operated and few were given adjuvant chemotherapy. Perioperative chemotherapy seems appropriate for biphasic and sarcomatoid varieties before surgery. Systemic chemotherapy is also warranted in lymph node metastasis and when the surgery is incomplete [8]. Our case is unique due to an attempt at resection prior to presentation and the presence of radiologically appearing metastatic nodes that persuaded us towards neoadjuvant chemotherapy. Secondly HIPEC was delivered because of the same reason, a re-operative case with violated planes and possibility of peritoneal dissemination during the previous partial resection and the overarching probability of a missed diffuse disease within the lesser sac obliterated by adhesions. HIPEC has emerged as the preferred mode of regional chemotherapy. Combination chemotherapy in HIPEC was shown to have better outcomes compared to single agent in 249 patients from the French database [9]. Even though regional chemotherapy would seem as overtreatment in most cases of purely localized mesotheliomas, the survivals have been dismal with surgery alone, based on the case reports of previous authors. In patients with good performance status, it seems advisable to discuss the option of HIPEC to reduce the chances of peritoneal recurrences in epithelioid mesothelioma. In this subgroup, local and peritoneal relapse is the most common site of failure where aggressive local treatment offers the best chance of disease control.

Conclusion

This is the first report of localized gastric mesothelioma in an adult. In addition our patient also presented with nodal metastasis without apparent visceral peritoneal involvement, which is extremely uncommon with mesotheliomas. Localized mesothelioma is potentially curable and aggressive surgery is warranted with selective use of perioperative and regional chemotherapy.

Abbreviations

CT

Computerized tomography

HIPEC

Hyperthermic intraperitoneal chemotherapy

PS

Performance status

Data availability

All data were retrieved from electronic medical records.

Code availability

Not applicable.

Declarations

Consent to participate

Consent was obtained from the patient for the present case report.

Compliance with ethical standards

The present study was in conformance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments. The institutional review board approval was exempted for case reports.

CARE guidelines

CARE guidelines were followed during drafting of this case report.

Conflicts of interest

The authors declare no competing interests.