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  Table of Contents    
CASE REPORT  
Year : 2017  |  Volume : 60  |  Issue : 3  |  Page : 421-423
Undiagnosed senile systemic amyloidosis with mesenteric angiopathy leading to fatal outcomes: Two case series with a review of literature


1 Department of Pathology, University of Michigan, Ann Arbor, MI, USA
2 Department of Pathology, University of Florida, College of Medicine, Jacksonville, FL, USA
3 Department of Forensic Medicine, Maulana Azad Medical College, New Delhi, India

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Date of Web Publication22-Sep-2017
 

   Abstract 

Amyloid mesenteric angiopathy is difficult to diagnose as gastrointestinal (GI) signs are nonspecific and radiological studies rarely identify amyloid deposits with certainty. The objective of this study was to highlight the pathological findings of amyloid mesenteric angiopathy in cases of senile systemic amyloidosis. Literature review, author's research data, and practice experience were used. Systemic amyloidosis should be considered in the differential diagnoses when evaluating nonspecific and unexplained GI in patient population aged >55 years to decrease the morbidity and fatal outcomes.

Keywords: Amyloid, angiopathy, mesentery

How to cite this article:
Gupta A, Tarbunova M, Aggrawal A, Aysola AE. Undiagnosed senile systemic amyloidosis with mesenteric angiopathy leading to fatal outcomes: Two case series with a review of literature. Indian J Pathol Microbiol 2017;60:421-3

How to cite this URL:
Gupta A, Tarbunova M, Aggrawal A, Aysola AE. Undiagnosed senile systemic amyloidosis with mesenteric angiopathy leading to fatal outcomes: Two case series with a review of literature. Indian J Pathol Microbiol [serial online] 2017 [cited 2019 Dec 14];60:421-3. Available from: http://www.ijpmonline.org/text.asp?2017/60/3/421/215369



   Introduction Top


Amyloidosis is a heterogeneous disease with multiple clinical manifestations that depend on the type and extent of the tissue deposition. One of the least frequently described presentations of amyloidosis is gastrointestinal (GI) symptoms, including lower GI bleeding and pseudo-obstruction of the large intestine. We describe two patients with generalized amyloidosis whose clinical presentation was dominated by GI symptoms.


   Case Reports Top


Case report 1

A 77-year-old male with a past medical history of hypertension, diabetes mellitus, hyperlipidemia, pulmonary hypertension, and coronary bypass surgery underwent elective arthroplasty of the right knee. His postoperative course was complicated by colonic pseudo-obstruction within the cecum measuring up to 16 cm on radiographs. Intraoperative findings included perforation of the ascending and transverse colon.

Autopsy findings were significant for bleeding into both the abdominal cavity and the right lower limb muscles. The large intestine showed ischemic changes with hemorrhage into the colonic mesentery [Figure 1]. The mesenteric blood vessels had prominent amyloid deposits into the vessel wall along with atherosclerotic changes of the medium-to-large-sized mesenteric arteries. Amyloid deposition was also found in the liver, heart, kidneys, and small blood vessels. These findings are consistent with systemic amyloidosis.
Figure 1: Microscopic section of the large intestine showing ischemic changes with hemorrhage into the colonic mesentery

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Case report 2

An 83-year-old African-American woman with a history of hypertension, diabetes mellitus, congestive heart failure, restrictive lung disease, and a remote history of bilateral pulmonary embolism was admitted with lower GI bleeding and non-ST elevation myocardial infarction. The source of bleeding was not revealed with either an angiogram or with a colonoscopy.

The autopsy findings were significant for the hemorrhagic segment of sigmoid colon with several diverticula along with cardiomegaly (heart weight: 750 g). Microscopic examination of the hemorrhagic colon revealed diverticulosis and amyloid depositions in the vessel walls. Amyloid deposition was present in the heart and lungs diffusely; findings that are consistent with systemic amyloidosis. The Congo red stain showed apple-green birefringence of amyloid deposits under polarized light [Figure 2].
Figure 2: Congo red stain showing apple-green birefringence of amyloid deposits within the mesenteric blood vessel under polarized light

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Paraffin-embedded tissues from both cases were submitted for amyloid subtyping. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed on peptides extracted from Congo red-positive/microdissected areas of paraffin-embedded heart specimens. LC-MS/MS detected a peptide profile consistent with transthyretin/prealbumin-type (ATTR) amyloid depositions in both cases.


   Discussion Top


Amyloidosis is a heterogeneous disorder, which is caused by the miss folding of extracellular proteins, resulting in abnormal deposition in solid organs. There are 27 different human and nine animal forms of amyloidosis based on classification of the (pro) precursors.[1]

Senile systemic amyloidosis (SSA) is a common age-related amyloidosis that is characterized by the accumulation of normal TTR in extracellular compartments of tissues and organs (heart, lungs, and vessel walls). Amyloid accumulation in the heart is frequently diagnosed as a restrictive cardiomyopathy and symptoms include congestive heart failure and conduction defects leading to arrhythmias. The incidence of pulmonary amyloidosis has been reported in up to 10% of patients older than 80 years of age and 50% of patients older than 90 years of age without significant symptoms.[2]

Regarding the GI tract involvement of systemic amyloidosis, the most frequent symptoms include macroglossia, motility disturbance causing pseudo-obstruction, bleeding, diarrhea, and malabsorption. Sattianayagam et al. reviewed the effect of systemic amyloidosis in the GI tract and emphasized the nonspecific clinical presentations, as well as the nonspecific endoscopic and radiological features of amyloid depositions in the GI tract.[3] Matsutani et al. found that, in patients over the age of 80 years, 45% have amyloid deposits in the lung or GI tract during autopsy. TTR amyloid deposits were seen both in arteries and veins in a patchy or nodular pattern.[4]

Andrews et al. reported a case similar to our cases of systemic amyloidosis, presenting as mesenteric angina.[5] Mesenteric angiography failed to explain the cause of mesenteric angina; superior and inferior mesenteric arteries were patent and did not have any evidence of atherosclerosis. Autopsy revealed systemic amyloid deposits with obliteration of the mesentery and bowel wall.

Elli et al. reported a case of megaduodenum as an unusual presentation of systemic amyloidosis leading to pseudo-obstruction.[6] Greenstein et al. found that amyloid deposits were present 4.4 times more often among people with Crohn's disease than other small bowel diseases.[7]

Patients with amyloidosis have an increased risk of bleeding; GI bleeding, in particular, can be the presenting symptom. Patients with systemic amyloidosis have been reported to show small vessel fragility due to deposits of amyloid within the blood vessel wall, resulting in major bleeding episodes in the GI tract. Since mesenteric angiopathy secondary to amyloid deposits is rarely seen on imaging studies, the diagnosis of amyloidosis causing GI bleeding is usually made later in the course of the disease or in a postmortem examination.[3]

In addition to vessel fragility, an acquired bleeding diathesis can increase the risk of GI bleeding in patients with systemic amyloidosis. Reduced factor X level has been reported in patients with amyloidosis as a rare cause leading to GI and other bleeding events.[8],[9],[10]

The acquired hemostatic abnormalities including coagulation factor deficiencies, increased fibrinolysis, and platelet dysfunction can be regarded as the most important pathogenic factors in patients with light-chain amyloidosis. The mechanism of the decreased factor X level is thought to be secondary to the binding of factor X to the amyloid fibrils.[8],[9],[10]

In our cases, two main mechanisms for the amyloidosis' role in morbidity and mortality are proposed. First is the role of GI amyloidosis, relevant to the patient's initial pseudo-obstruction and subsequent perforation. Second and more importantly is the role of microvascular amyloid deposition and vascular fragility responsible for the spontaneous life-threatening GI bleeding and an inability to complete hemostasis following surgery.

The possibility of systemic amyloidosis is often overlooked, resulting in substantial delays in diagnosis. A high index of suspicion is required, as it could lead to the timely diagnosis of SSA and prepare the physician for potential complications. Our cases indicate that SSA should be in the differential diagnoses when evaluating nonspecific, and unexplained, GI and cardiopulmonary symptoms in elderly patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Pettersson T, Konttinen YT. Amyloidosis-recent developments. Semin Arthritis Rheum 2010;39:356-68.  Back to cited text no. 1
    
2.
Pitkänen P, Westermark P, Cornwell GG 3rd. Senile systemic amyloidosis. Am J Pathol 1984;117:391-9.  Back to cited text no. 2
    
3.
Sattianayagam PT, Hawkins PN, Gillmore JD. Systemic amyloidosis and the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 2009;6:608-17.  Back to cited text no. 3
    
4.
Matsutani H, Hoshii Y, Setoguchi M, Kawano H, Gondo T, Takahashi M, et al. Vascular amyloid of unknown origin and senile transthyretin amyloid in the lung and gastrointestinal tract of old age: Histological and immunohistochemical studies. Pathol Int 2001;51:326-32.  Back to cited text no. 4
    
5.
Andrews CN, Amar JN, Hayes MM, Enns RA. Systemic amyloidosis: A rare presentation of mesenteric angina. Can J Gastroenterol 2002;16:683-5.  Back to cited text no. 5
    
6.
Elli L, Falconieri G, Bardella MT, Caldato M, Pizzolitto S, Bonura A, et al. Megaduodenum: An unusual presentation of amyloidosis? Acta Gastroenterol Belg 2010;73:287-91.  Back to cited text no. 6
    
7.
Greenstein AJ, Sachar DB, Panday AK, Dikman SH, Meyers S, Heimann T, et al. Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. Medicine (Baltimore) 1992;71:261-70.  Back to cited text no. 7
    
8.
Manikkan AT. Factor X deficiency: An uncommon presentation of AL amyloidosis. Ups J Med Sci 2012;117:457-9.  Back to cited text no. 8
    
9.
Sucker C, Hetzel GR, Grabensee B, Stockschlaeder M, Scharf RE. Amyloidosis and bleeding: Pathophysiology, diagnosis, and therapy. Am J Kidney Dis 2006;47:947-55.  Back to cited text no. 9
    
10.
Enjeti AK, Walsh M, Seldon M. Spontaneous major bleeding in acquired factor X deficiency secondary to AL-amyloidosis. Haemophilia 2005;11:535-8.  Back to cited text no. 10
    

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Correspondence Address:
Avneesh Gupta
Department of Pathology, Division of Neuropathology, 1301 Catherine Street, Room 5226 Med SCI I, Ann Arbor, MI 48109
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_278_16

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