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Year : 2023  |  Volume : 66  |  Issue : 3  |  Page : 594-596
Secondary amyloidosis with concomitant gastric GIST and gastric adenocarcinoma - A case report

1 Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Surgical Oncology, Mohandai Oswal Hospital, Ludhiana, Punjab, India

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Date of Submission10-May-2021
Date of Decision14-Jun-2021
Date of Acceptance14-Jun-2021
Date of Web Publication07-Jun-2022


Secondary amyloidosis is a well-established entity and has been described in association with chronic inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, bronchiectasis, tuberculosis, etc., It has also been reported in association with neoplasms such as Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, renal cell carcinoma, lung carcinoma, etc. However, only a few case reports documenting the association of amyloidosis with gastrointestinal tumor (GIST) and gastric adenocarcinoma are available in the literature. Hereby, we report a case of a 74-year-old male who presented with colicky abdominal pain and vomiting. Ultrasonography revealed a common bile duct (CBD) stone and a small extra-luminal gastric mass. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to remove the CBD stone which revealed an incidental finding of gastric ulcer. A biopsy was taken from the gastric ulcer which on histopathological examination was confirmed as adenocarcinoma leading onto total gastrectomy. During total gastrectomy, an inadvertent injury to the spleen led to simultaneous splenectomy. Multiple samples from the gastric ulcer, the extra-luminal gastric mass, and the spleen were subjected to histopathological examination. Gastric ulcer was confirmed as adenocarcinoma, gastric extra-luminal mass was confirmed as GIST, and splenic examination revealed widespread deposition of amyloid which on Congo-red stain imparted an apple-green birefringence on polarizing microscopy. To the best of our knowledge, this is the first-ever case of such an association where gastric adenocarcinoma occurred with concomitant gastric GIST and secondary amyloidosis of the spleen.

Keywords: AA Amyloidosis, chronic inflammatory conditions, gastric adenocarcinoma, GIST, secondary amyloidosis

How to cite this article:
Soni A, Batta N, Mehmi S, Narang V, Garg B, Kaur H. Secondary amyloidosis with concomitant gastric GIST and gastric adenocarcinoma - A case report. Indian J Pathol Microbiol 2023;66:594-6

How to cite this URL:
Soni A, Batta N, Mehmi S, Narang V, Garg B, Kaur H. Secondary amyloidosis with concomitant gastric GIST and gastric adenocarcinoma - A case report. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Sep 23];66:594-6. Available from:

   Introduction Top

Secondary amyloidosis is defined as extracellular deposition of serum amyloid A (SAA) protein as insoluble fibrils. It is an acute-phase reactant produced by the liver in chronic inflammatory conditions such as tuberculosis, osteomyelitis, bronchiectasis, rheumatoid arthritis, etc. It is uncommonly coupled with neoplasm such as Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, renal cell carcinoma, lung carcinoma, etc.[1] However, the association with gastrointestinal stromal tumor (GIST) is rare and is even rarer with gastric adenocarcinoma. This case is unique as it demonstrates a rare coexistence of gastric GIST, gastric adenocarcinoma, and splenic amyloidosis.

   Case Report Top

A 74-year-old male complained of pain in the abdomen of 2 months duration which was intermittent, colicky, used to get aggravated on a fatty meal, and associated with vomiting. General physical examination revealed pedal edema. Complete blood count revealed –hemoglobin- 8.0 g/dL, total leucocyte count- 6 × 103/μL, and platelets- 200 × 103/μL. Peripheral blood film showed microcytic hypochromic red blood cells (RBCs) with few normocytes, elliptocytes, and teardrop cells. Urine examination revealed nephrotic range proteinurea, RBCs (5–6/hpf), and WBCs (8–10/hpf). Abdominal ultrasonography revealed the presence of a stone in the common bile duct (CBD) along with a well-defined hypoechoic extra-luminal mass in the stomach having sharply delineated margins measuring 0.5 × 0.4 × 0.4 cm. Stone removal by endoscopic retrograde cholangiopancreatography (ERCP) was done, and a stent was placed in the CBD. During ERCP, an ulcer was incidentally identified in the fundus of the stomach measuring 2 × 1.4 ×1 cm. Endoscopic gastric ulcer biopsy rendered the diagnosis of adenocarcinoma of the stomach, which guided towards total gastrectomy. During the surgery, an inadvertent injury to the spleen resulted in simultaneous splenectomy.

Grossly, an ulcer was identified in the fundus of the stomach measuring 2 × 1.5 × 0.6 cm along with a solid nodule at the serosal aspect of the body of the stomach measuring 0.5 × 0.5 × 0.3 cm. The spleen measured 9 × 5 × 3 cm with the cut surface showing numerous whitish map-like areas. Histopathological examination of the gastric ulcer showed adenocarcinoma seen as irregular glands lined by cells exhibiting nuclear stratification and hyperchromasia, which was infiltrating up to the muscularis propria [Figure 1]a.
Figure 1: Photomicrograph showing gastric adenocarcinoma (a; Hematoxylin and eosin stain; ×100); photomicrograph showing gastric GIST (b; Hematoxylin and eosin stain; ×100) exhibiting immunopositivity for DOG1 (c; IHC; ×400), CD34 (d; IHC; ×400), and SMA (e; IHC; ×400)

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Serosal nodule showed a spindle cell neoplasm with insignificant nuclear atypia and mitosis (<5/50hpf) [Figure 1]b. On immunohistochemistry (IHC), it showed immunopositivity for discovered on gastrointestinal stromal tumors (DOG)-1 [Figure 1]c, CD-34 [Figure 1]d, and focal smooth muscle actin (SMA) [Figure 1]e, and immunoreactivity for S-100, thus confirming the diagnosis of gastrointestinal stromal tumor (GIST) with prognostic group 1.

Histopathological examination of the spleen showed extensive deposition of eosinophilic acellular hyaline-like material (amyloid) within the sinusoids [Figure 2]a which on Congo-red staining imparted congophilia on light microscopy [Figure 2]b and an apple green birefringence on polarized microscopy [[Figure 2]b inset].
Figure 2: Photomicrograph showing extensive deposition of amorphous eosinophilic acellular material (amyloid) within the splenic sinusoids (a; Hematoxylin and eosin stain; ×100) which is exhibiting congophilia on congo red stain on light microscopy (b; Congo red stain; ×100) and apple-green birefringence on congo red stain on polarizing microscopy (b inset; Congo red stain; ×100)

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   Discussion Top

Amyloidosis is defined as the extracellular deposition of proteinaceous material as insoluble fibrils leading to organ dysfunction. Approximately 25 proteins have been described to be associated with amyloidosis. Depending on the protein deposited, various forms of amyloidosis have been identified.[1] Secondary amyloidosis [also called systemic amyloid A (AA) amyloidosis or reactive amyloidosis] occurs due to deposition of serum amyloid A (SAA) protein which is an acute phase reactant and produced by the liver in chronic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, osteomyelitis, tuberculosis, vasculitis, Hodgkin's lymphoma, etc. Brunger et al. reviewed the literature extensively and provided a comprehensive list of causes of AA amyloidosis. Among the neoplastic conditions, lung carcinoma, mesothelioma, renal cell carcinoma, and hepatocellular adenoma were shown to have a strong causative association. Week association was described in carcinoma of esophagus, pancreas, colorectum, prostate, urinary bladder, and paragangliomas. A limited number of AA amyloidosis cases have been reported in association with gastrointestinal stromal tumor (GIST) and carcinoma of the stomach, uterus, and ovary.[2] To the best of our knowledge, three cases each of GIST[3],[4],[5] and gastric adenocarcinoma[6],[7],[8] have been reported in association with secondary amyloidosis to date. Our case is unique as it first time describes synchronous gastric GIST and gastric adenocarcinoma in association with secondary amyloidosis. Splenic amyloidosis was documented on histopathology and polarizing microscopy on the Congo-red stain, and renal involvement was suspected due to the nephrotic range proteinurea. An extensive work-up was carried out to rule out any other cause of secondary amyloidosis before attributing it to the neoplastic pathology in our case.

Tumor-mediated inflammation leads to increased production of SAA in the liver which in conjunction with other factors such as amyloid-enhancing factor (AEF) and inhibited monocyte-mediated SAA degradation causes protein (SAA) misfolding and deposition in highly vascular organs such as the spleen, liver, kidney, and adrenal[6]. Secondary amyloidosis in association with carcinoma of the lung and kidney is well documented. However, it has rarely been reported in association with either GIST or gastric adenocarcinoma. In fact, synchronous gastric GIST and gastric adenocarcinoma is also an uncommon affair.

Excision of the tumor remains the mainstay of treatment for primary neoplasm as well as for associated secondary amyloidosis. It may halt the deposition of misfolded AA protein and sometimes even reverse it, which was noted in our case also seen a a decline in proteinuria after the surgical resection of the tumor.

   Conclusion Top

Secondary amyloidosis occurring in an association of synchronous gastric adenocarcinoma and gastric GIST led us to report this case for its rarity and as an addition to the literature. Awareness of such an association and a clinical suspicion may help in the timely management of the possible renal complications related to secondary amyloidosis. Yet, the prognosis depends on the reversibility of both the primary neoplasm and the renal complications.

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.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med 2007;356:2361-71.  Back to cited text no. 1
Brunger AF, Nienhuis HL, Bijzet J, Hazenberg BP. Causes of AA amyloidosis: A systematic review. Amyloid 2020;27:1-12.  Back to cited text no. 2
Muñiz-Pacios L, Morales-Ruiz E, Aguilar F, García-Martín F. Chronic renal failure secondary to systemic amyloidosis associated with gastrointestinal stromal tumour. Nefrologia 2013;33:620-2.  Back to cited text no. 3
Overstreet K, Barone RM, Robin HS. Secondary amyloidosis and gastrointestinal stromal tumors. A case report and discussion of pathogenesis. Arch Pathol Lab Med 2003;127:470-3.  Back to cited text no. 4
Jaakkola H, Törnroth T, Groop PH, Honkanen E. Renal failure and nephrotic syndrome associated with gastrointestinal stromal tumour (GIST)-a rare cause of AA amyloidosis. Nephrol Dial Transplant 2001;16:1517-8.  Back to cited text no. 5
Aoyagi K, Koufuji K, Yano S, Murakami N, Miyagi M, Koga A, et al. Early gastric carcinoma associated with amyloidosis: A case report. Kurume Med J 2002;49:153-6.  Back to cited text no. 6
Chang DZ, Zhang JX, Filippa DA, Portlock CS. Unusual abdominal tumors, case 2. Localized amyloid associated with gastric adenocarcinoma. J Clin Oncol 2004;22:1520-2.  Back to cited text no. 7
Ersoy A, Filiz G, Ersoy C, Kahvecioglu S, Kanat O, Vuruskan H, et al. Synchronous carcinomas of stomach and bladder together with AA amyloidosis. Nephrology (Carlton) 2006;11:120-3.  Back to cited text no. 8

Correspondence Address:
Vikram Narang
Department of Pathology, Dayanand Medical College and Hospital, Tagore Nagar, Ludhiana - 141 001, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_461_21

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