Gastric Amyloidosis Mimicking a Gastric Neoplasm

Amyloidosis is a systemic disorder caused by extracellular deposition of insoluble abnormal amyloid fibrils, interfering with normal tissue and organ function. The type of protein that is misfolded and the organ or tissue in which they are deposited determine the clinical manifestations of amyloidosis. The term “amyloid” was first used by Virchow to describe an abnormal material seen in the liver on autopsy. It was later recognized that this material appeared apple-green under polarized light with Congo red staining [1]. Electron microscopy showed a common fibrillar nature and beta pleated sheet structure that was key to the pathogenesis of disease. Various historical classification systems were based on clinical findings or the distribution of organ involvement.


Introduction
Amyloidosis is a systemic disorder caused by extracellular deposition of insoluble abnormal amyloid fibrils, interfering with normal tissue and organ function.The type of protein that is misfolded and the organ or tissue in which they are deposited determine the clinical manifestations of amyloidosis.The term "amyloid" was first used by Virchow to describe an abnormal material seen in the liver on autopsy.It was later recognized that this material appeared apple-green under polarized light with Congo red staining [1].Electron microscopy showed a common fibrillar nature and beta pleated sheet structure that was key to the pathogenesis of disease.Various historical classification systems were based on clinical findings or the distribution of organ involvement.

Case
We present an 85-year-old man who was admitted to our hospital with history of anemia and with chief complains of epigastric pain and weight loss.He also described reflux symptoms with early satiety and post-meal vomiting.No personal history, only he has hypertension and hyperlipidemia (for which he is medicated with captopril and simvastatin, respectively).No medical history of diabetes mellitus or neoplasms.Physical examination on admission revealed normal vital signs and a soft and non-tender abdomen.Initial investigations revealed normochromic and normocytic anemia, with a hemoglobin level of 11.8 g/dl (normal range, 13-17 g/dl).Other laboratory blood examinations (summarized in table 1) showed no abnormality in routine test, including urinalysis, liver, kidney and thyroid function and autoimmune screen.
Esophagogastroduodenoscopy revealed a thickened irregular fold in the antrum, which closely resembled gastric malignancy, without ulceration (Figure 1).He was submitted to a colonoscopy, with normal appearance of the mucosa.Multiple biopsies from esophagus, stomach (including the suspect area of the antrum), duodenum, terminal ileum and colon were performed.Histopathologic examination with hematoxylin and eosin staining of gastric mucosa showed an extensive deposition of pink amorphous, eosinophilic homogeneous masses in the lamina propria.These masses are orange-red with Congo red staining under the light microscopy and showed apple-green birefringence under polarized light.It was imunoreactive for A amyloid (Figure 2).There were no amyloid deposits in the rest of the gastrointestinal tract.The diagnosis of localized gastric amyloidosis with AA type amyloid deposition was made.
The potential for secondary systemic amyloidosis was then investigated with serum and urine protein electrophoresis.Laboratory data showed negative results in the detection of serum  A left ventricular hypertrophy, with normal ejection fraction was noted upon echocardiography.Ultrasound of the abdomen and pelvis showed no evidence of systemic amyloidosis.Computed tomography scan of the chest, abdomen and pelvis showed no remarkable findings in other organs.The available follow-up data showed an indolent course.He had no evidence of chronic disorders predisposing him to secondary amyloidosis or amyloid deposition, such as rheumatoid arthritis, tuberculosis, cardiac disease, Local deposition of amyloid in the gastrointestinal system without systemic involvement is an uncommon form [5].The clinical manifestations of gastric amyloidosis are often uncharacteristic and subclinical.It varied including dysphagia, abdominal pain, poor appetite, nausea, gastroparesis, diarrhea, obstipation, pseudoobstruction, malabsorption, hematemesis, weight loss and gastric perforation.Gastrointestinal symptoms are very unusual, occurring in less than 1% of patients [2].The endoscopic appearance of gastric amyloidosis is not specific and it can closely resemble a gastric malignancy.Amyloidosis can appear as submucosal tumors, polyps, thickened irregular fold or gastric ulcer associated with gastrointestinal bleeding [6].
It is recommended to asses for progression to systemic amyloidosis on a regular basis.This should include a full history and physical examination along with electrocardiogram, complete blood count, serum creatinine levels, serum liver-associated enzyme levels, serum electrophoresis, and urine examination.
Definitive diagnosis of amyloidosis depends on histological examination of the affected tissue or organ.Treatment of amyloidosis is often difficult and it remains unsatisfactory.Therapy depends on early diagnosis and a correct distinction classification of type of amyloid [7].The treatment of gastric involvement is primarily symptomatic.Currently, there are no published reports that mention any specific therapy for localized gastric amyloidosis in particular.The treatment strategy has been directed both to support the affected organs and to deal with the underlying specific disease in an attempt to reduce the deposition of amyloidal substances and improve prognosis, in which several supportive multiple myeloma, malabsorption, and proteinuria.In the absence of investigation findings for secondary systemic amyloidosis, the condition was classified as primary gastric amyloidosis in conjunction with histopathology findings.
The patient was programmed for regular check-up with blood test and several biopsies from the abdominal fat and gastrointestinal tract in the follow-up of six months to detect a potential progress to systemic disease.No other deposit locations have been found.He continued to be in good condition with no findings of disease progression one year after verification of our diagnosis.

Discussion
Historically, amyloidosis was classified clinically into systemic, with involvement of several organs, and localized, in which deposits are limited to a single organ.The modern classification is based on the type of precursor protein involved.The most common forms of amyloidosis are amyloid light-chain (AL or primary systemic); amyloid A (AA or secondary systemic); and familial (abnormal amyloid transthyretin [ATTR] [2].At present, there are 30 structurally unrelated proteins that are known to cause amyloidosis [3].
Generally, amyloidosis is more commonly manifested as a systemic involvement of multiple tissues and organs including the heart, liver, spleen, kidneys, lymph nodes, adrenals, thyroid, as well as many others.Gastrointestinal tract is one of the regions to be commonly involved in the systemic amyloidosis.Localized deposition of amyloid is a rather uncommon form, but can be seen in many different anatomic regions including tongue, skin, breast, nervous system, respiratory, genitourinary and gastrointestinal tracts.Amyloidal deposit confined to the stomach is extremely rare [4].protocols and chemotherapeutic drugs including melphalan and colchicine have been widely used, although their effectiveness in ameliorating this disease has remained to be determined [5].Some reports have documented that surgical resection with lymph node dissection may be a therapeutic strategy to prevent possible complications such as bleeding and obstruction [8].With the advances in molecular biology, some promising attempts have been made to reduce inflammatory response and amyloidal deposits by blocking the signal conduction of RAGE-NF-κB in monocytes/ macrophages [9].In contrast, some authors no deem to be necessary any treatment if the patient is symptom free on clinical follow-up and periodic controls should be scheduled to follow the evolution of the disease [10].
In our case, probably the preferable therapeutic modality would be a surgical resection, but the patient refused to undergo surgery.He consented to treated with a proton pump inhibitor (pantoprazole) 40 mg/day orally, prednisone 20 mg/day, melphalan and colchicine.
The prognosis of amyloidosis differs according to type and the involved organs.Systemic amyloidosis is usually with an unfavorable prognosis while the localized types of this disease such as the localized gastric amyloidosis have a relatively better outcome.AL amyloidosis has a poor prognosis with a median survival of one to two years [5].The prognosis of AA amyloidosis differs according to the underlying disease [11].

Conclusion
We present this case to highlight the importance of considering an infiltrative systemic disorder for gastrointestinal symptoms and weight loss.We want to emphasize that amyloidosis, although rare, can initially present with predominantly gastrointestinal symptoms alone.It is important for the internist and gastroenterologist to consider amyloidosis as a differential diagnosis in the investigation of organ dysfunction.

Figure 1 :
Figure 1: Endoscopic appearance of gastric amyloidosis showed a thickened fold in the gastric antrum.

Table 1 :
Laboratory data summary.