Gastric Adenocarcinoma in a Patient with Tuberous Sclerosis Complex: A Rare Case Report and Review of Literature

Ramya Ravichandar¹, Rajam Krishna S², Priya Sivashankar3, and Sujai Anand*⁴

This case determines a rare co-occurrence of gastric adenocarcinoma in a TSC patient, urging consideration of malignancies in TSC management.

Abstract

Background: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign tumors in multiple organ systems. Caused by mutations in TSC1 or TSC2 genes, TSC primarily leads to benign growths, but rare malignancies have been reported. Malignancies in TSC patients are uncommon, and the association with gastric adenocarcinoma is exceedingly rare. This report presents a case of gastric adenocarcinoma in a 42-year-old male with TSC, highlighting the need for awareness of potential malignancies in TSC patients. Method: The patient, a known case of TSC, presented with swelling in the left axilla, significant weight loss, and reduced appetite. An excision biopsy of the axillary lymph nodes was performed to evaluate the swelling. An upper gastrointestinal (UGI) endoscopy was conducted to identify the primary malignancy source. Results: Histopathological examination of the excised axillary lymph nodes revealed secondary deposits of adenocarcinoma. UGI endoscopy identified multiple polypoidal lesions in the stomach. Biopsy of these lesions confirmed poorly cohesive adenocarcinoma of the signet ring cell type, a subtype of diffuse-type gastric adenocarcinoma. Conclusion: This case illustrates a rare occurrence of gastric adenocarcinoma in a TSC patient, suggesting the possibility of an under-recognized association. Further studies are needed to explore this potential link, which could impact the surveillance and management of TSC patients, particularly those presenting with atypical symptoms.

Keywords: Tuberous sclerosis complex, Gastric adenocarcinoma, Signet ring cell carcinoma, mTOR pathway, Genetic disorder.

References

Ahmed, S., Burney, I., Sawhney, S., & Al-Moundhri, M. S. (2009). Gastric adenocarcinoma in association with tuberous sclerosis: Case report. Sultan Qaboos University Medical Journal, 9(1), 75-78.

Borkowska, J., Schwartz, R. A., Kotulska, K., & Jozwiak, S. (2011). Tuberous sclerosis complex: Tumors and tumorigenesis. International Journal of Dermatology, 50(1), 13–20. https://doi.org/10.1111/j.1365-4632.2010.04600.x

Brook-Carter, P. T., Peral, B., Ward, C. J., Thompson, P., Hughes, J., Maheshwar, M. M., ... & Harris, P. C. (1994). Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease—a contiguous gene syndrome. Nature Genetics, 8(4), 328–332. https://doi.org/10.1038/ng1094-328

Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006). The tuberous sclerosis complex. New England Journal of Medicine, 355(13), 1345–1356. https://doi.org/10.1056/NEJMra055160

Dabora, S. L., Jozwiak, S., Franz, D. N., Roberts, P. S., Nieto, A., Chung, J., ... & Thiele, E. A. (2001). Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. American Journal of Human Genetics, 68(1), 64–80. https://doi.org/10.1086/316969

Ekong, R. (n.d.). The TSC1 gene homepage: Global Variome. Retrieved from https://databases.lovd.nl/shared/genes/TSC1

Ekong, R. (n.d.). The TSC2 gene homepage: Global Variome. Retrieved from https://databases.lovd.nl/shared/genes/TSC2

Eledrisi, M. S., Stuart, C. A., & Alshanti, M. (2002). Insulinoma in a patient with tuberous sclerosis: Is there an association? Endocrine Practice, 8(2), 109–112. https://doi.org/10.4158/EP.8.2.109

Gupta, S., Kang, H. C., Faria, S. C., Choyke, P. L., & Kundra, V. (2022). Tuberous sclerosis complex (TSC): Renal and extrarenal imaging. Academic Radiology, 29(3), 439–449. https://doi.org/10.1016/j.acra.2021.08.014

Gupta, S., Stanton, M. L., Reynolds, J. P., Whaley, R. D., Herrera-Hernandez, L., Jimenez, R. E., ... & Marzban, S. S. (2022). Lessons from histopathologic examination of nephrectomy specimens in patients with tuberous sclerosis complex: Cysts, angiomyolipomas, and renal cell carcinoma. Human Pathology, 129, 123–139. https://doi.org/10.1016/j.humpath.2022.06.009

Habib, S. L., Al-Obaidi, N. Y., Nowacki, M., Pietkun, K., Zegarska, B., Kloskowski, T., ... & Rej, P. (2016). Is mTOR inhibitor good enough for treatment all tumors in TSC patients? Journal of Cancer, 7(12), 1621–1631. https://doi.org/10.7150/jca.16978

Jones, A. C., Shyamsundar, M. M., Thomas, M. W., Maynard, J., Idziaszczyk, S., Tomkins, S., ... & Evans, J. (1999). Comprehensive mutation analysis of TSC1 and TSC2—and phenotypic correlations in 150 families with tuberous sclerosis. American Journal of Human Genetics, 64(5), 1305–1315. https://doi.org/10.1086/302520

Kim, B. K., Kim, Y. I., & Kim, W. H. (2000). Hamartomatous gastric polyposis in a patient with tuberous sclerosis. Journal of Korean Medical Science, 15(4), 467-470. https://doi.org/10.3346/jkms.2000.15.4.467

Lendvay, T. S., & Marshall, F. F. (2003). The tuberous sclerosis complex and its highly variable manifestations. The Journal of Urology, 169(5), 1635-1642. https://doi.org/10.1097/01.ju.0000058253.40352.60

Northrup, H., Aronow, M. E., Bebin, E. M., Bissler, J., Darling, T. N., de Vries, P. J., ... & Thiele, E. A. (2021). Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatric Neurology, 123, 50–66. https://doi.org/10.1016/j.pediatrneurol.2021.04.001

Northrup, H., Koenig, M. K., Pearson, D. A., & Au, K. S. (1993). Tuberous sclerosis complex. In M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews. Seattle (WA): University of Washington.

Oh, S. J., Oh, C. A., Kim, D. H., Choi, M. G., Noh, J. H., Sohn, T. S., ... & Kim, S. (2011). Adenocarcinoma derived from gastric hamartomatous polyps. Journal of the Korean Surgical Society, 81(6), 419-422. https://doi.org/10.4174/jkss.2011.81.6.419

Orosz, P., Kollák, Z., Petho, Á., Fogarasi, A., Reusz, G., Hadzsiev, K., ... & Róka, R. (2023). The importance of genetic testing in the differential diagnosis of atypical TSC2-PKD1 contiguous gene syndrome-case series. Children, 10(3), 420. https://doi.org/10.3390/children10030420

Rosset, C., Netto, C. B. O., & Ashton-Prolla, P. (2017). TSC1 and TSC2 gene mutations and their implications for treatment in tuberous sclerosis complex: A review. Genetics and Molecular Biology, 40(1), 69–79. https://doi.org/10.1590/1678-4685-GMB-2016-0204

Sauter, M., Belousova, E., Benedik, M. P., Carter, T., Cottin, V., Curatolo, P., ... & Kwiatkowski, D. J. (2021). Rare manifestations and malignancies in tuberous sclerosis complex: Findings from the TuberOus SClerosis registry to increase disease awareness (TOSCA). Orphanet Journal of Rare Diseases, 16(1), 301. https://doi.org/10.1186/s13023-021-01880-6

Tatsuta, M., Okuda, S., Tamura, H., & Taniguchi, H. (1980). Gastric hamartomatous polyps in the absence of familial polyposis coli. Cancer, 45(4), 818-823. https://doi.org/10.1002/1097-0142(19800215)45:4<818::AID-CNCR2820450435>3.0.CO;2-5