Year : 2009 | Volume
: 52 | Issue : 4 | Page : 530--533
Nodular lymphoid hyperplasia in common variable immunodeficiency syndrome mimicking familial adenomatous polyposis on endoscopy
Mahsa Molaei, Alireza Kaboli, Alireza Modares Fathi, Reza Mashayekhi, Shervin Pejhan, Mohammad Reza Zali
Department of Pathology and Gastroenterology, Research Center for Gastroenterology and Liver Disease, Shaheed Beheshti University (M.C), Tehran, Iran
Research Center for Gastroenterology and Liver Disease, Shaheed Beheshti University (M.C), Tehran
Common variable immunodeficiency syndrome (CVID) includes a heterogeneous disorder characterized by reduced levels of IgG, IgA or IgM, and recurrent bacterial infections with normal T-cell immunity in 60% of patients. It affects the gastrointestinal tract as the largest immune organ with a wide spectrum of symptoms and signs. We present a case of nodular lymphoid hyperplasia (NLH) of the small intestine in a 31-year-old man admitted for evaluation of chronic diarrhea. Upper and lower gastrointestinal endoscopy revealed multiple polyps in the stomach, duodenum, ileum, and large intestine mimicking familial adenomatous polyposis (FAP). Although he had no history of recurrent infection, immunological profiles were in favor of CVID. We emphasize the importance of considering CVID in any patient with gastrointestinal manifestations even in the absence of recurrent bacterial infections. Diagnostic delay results in more morbidity and complications in untreated patients.
|How to cite this article:|
Molaei M, Kaboli A, Fathi AM, Mashayekhi R, Pejhan S, Zali MR. Nodular lymphoid hyperplasia in common variable immunodeficiency syndrome mimicking familial adenomatous polyposis on endoscopy.Indian J Pathol Microbiol 2009;52:530-533
|How to cite this URL:|
Molaei M, Kaboli A, Fathi AM, Mashayekhi R, Pejhan S, Zali MR. Nodular lymphoid hyperplasia in common variable immunodeficiency syndrome mimicking familial adenomatous polyposis on endoscopy. Indian J Pathol Microbiol [serial online] 2009 [cited 2021 Dec 4 ];52:530-533
Available from: https://www.ijpmonline.org/text.asp?2009/52/4/530/56152
Common variable immunodeficiency (CVID) is a syndrome characterized by hypogammaglobulinemia with phenotypically normal B cells. It is also known as acquired hypogammaglobulinemia because of a generally later age of onset of infections.  The majority of patients have at least one episode of pneumonia prior to diagnosis. 
The age at the onset of symptoms is variable, ranging from childhood to late adulthood, with some evidence of a bimodal distribution demonstrating peaks between 1 and 5 years and 18 and 25 years. 
Most cases of CVID are sporadic or follow an autosomal dominant pattern of inheritance, although there have been patients found who had an autosomal recessive pattern of inheritance. Other patients with a clinical presentation of CVID have mutations involving intermediates in B-cell-signaling and developmental pathways. Specifically, defects in CD19, BAFF-R, and TACI have been identified in such patients. 
The gastrointestinal manifestations of CVID are variable and tend to mimic diseases like chronic-atrophic gastritis, chronic giardiasis, intestinal malabsorption, nodular lymphoid hyperplasia (NLH), and pernicious anemia. 
Biopsy and resection specimens from the small bowel demonstrate a wide range of morphologic changes, from marked villous atrophy and increased lymphocytes in surface epithelium resembling celiac sprue, to nodular lymphoid hyperplasia and lymphoma. 
Patients may first present with symptoms and signs of diarrhea, malabsorption, and weight loss. Malabsorption and diarrhea occur in 9 to 40% of patients with CVID. In those with diarrhea, an infectious etiology is rarely confirmed. 
Many studies continue to confirm a high prevalence of inflammatory, malignant, and infectious gastrointestinal disorders in patients with CVID. The T-cell-mediated defects of this immunodeficiency disorder are thought to be the cause of majority of the gastrointestinal disorders in CVID. Therefore, intravenous immunoglobulin alone may be ineffective. Combination therapy with immunomodulators, such as azathioprine and 6-mercaptopurine, may be needed to treat these gastrointestinal manifestations of CVID. 
A 31-year-old male was referred to our hospital because of weight loss and chronic watery diarrhea since childhood. Diarrhea had both small and large intestinal characteristics, and did not change with fasting. During the last year he had a marked weight loss (26 kg), and two episodes of bloody diarrhea. There had not been any history of recurrent infections, such as sinusitis, bronchitis, pneumonia or otitis. The physical examination and laboratory data were unremarkable except for serum immunoglobulin levels which were as follows: IgG= 600 mg/dl, IgA= 63 mg/dl, and IgM=36 mg/dl. Anti HIV 1 and 2 antibodies were not detected. Stool examination showed blastocystis hominis, and stool cultures were negative.
The endoscopic diagnosis of the gastroenterologist was familial adenomatous polyposis [Figure 1] and he referred the patient to a surgeon for further evaluation and preparation for colectomy.
Multiple biopsies were taken from stomach, duodenum, terminal ileum, and colon mucosa. The specimens were sent in 10% buffered formalin to the pathology department. They were processed, embedded in paraffin block and sections were stained with hematoxylin and eosin for microscopic examination.
All specimens had intact surface epithelium and were free from dysplastic changes. There was a mild increase in lymphocytic infiltration of lamina propria of gastric mucosa without atypical lymphocytes and lymphoepithelial lesions. In small bowel mild villous blunting and atrophy without crypt hyperplasia was seen. The number of intraepithelial lymphocytes was within normal range. Mild architectural distortion of colon mucosa, associated with paneth cell metaplasia and lymphocyte and neutrophile infiltration in the lamina propria was observed. But the most prominent feature was the presence of multiple large lymphoid follicles, mostly containing germinal centers in the lamina propria and submucosa of gastric, duodenal and colonic biopsies [Figure 2]. Meticulous high power examination of lamina propria revealed that plasma cells were absent in inflammatory infiltrates. H. pylori colonization was observed in gastric pits and Giardia trophozoites in the duodenal specimen. The pathologic diagnosis of nodular lymphoid hyperplasia was made. The results of laboratory tests are listed in [Table 1]. CVID was diagnosed by reduction of serum IgA and IgM levels in this patient and the treatment by intravenous immunoglobulin (IVIG) was started.
Although somewhat heterogeneous in clinical presentation and manifestations, CVID is recognized as the most prevalent primary immunodeficiency disease, excluding selective IgA deficiency. It is characterized by hypogammaglobulinemia and recurrent sinopulmonary infections, chronic diarrhea, with an enhanced risk for malignancy, granulomatous disease, and joint involvement. ,,
There is a high prevalence of inflammatory, malignant, and infectious gastrointestinal disorders in patients with CVID. These include nodular lymphoid hyperplasia, which was reported in our case, inflammatory bowel disease (ulcerative colitis, ulcerative proctitis, or Crohn's disease), sprue-like illness with flat villi, pernicious anemia, giardiasis, and non-specific malabsorption. Defects in cellular immunity, rather than antibody deficiency alone, appear to predispose patients to such illnesses. 
Although it is mentioned that acute, chronic or recurrent infections, specifically pneumonia, bronchitis, sinusitis, conjunctivitis, and otitis, are observed in practically all patients with CVID;  patients may first present with symptoms and signs of diarrhea, malabsorption, and weight loss, as it was noted in our patient.  Malabsorption and diarrhea occur in 9 to 40% of patients with CVID. 
In severe cases, patients may suffer from symptoms of malabsorption, such as vitamin and electrolyte deficiencies.
Malabsorption involves dietary fat, carbohydrates, vitamin B12, and folate. Small intestinal biopsies show either sprue-like histologic features, including villous shortening with increased number of lymphocytes in the epithelium and in the lamina propria, or a pattern similar to graft-versus-host disease. 
In addition, nodular lymphoid hyperplasia can be detected in the gastrointestinal tract in a high proportion of CVID patients. It does not correlate with the presence of malabsorption and in contrast to non-immune compromised patients, plasma cells are not present in the extra mantle zones. However, the pathogenesis of most lesions in the gastrointestinal tract of these patients remains unknown. 
It is important to consider CVID in any patient with gastrointestinal manifestations especially chronic diarrhea being associated with recurrent bacterial infections of other organs or not. Such patients should undergo a full assessment of immune system. Diagnostic delay results in more morbidity and complications in untreated patients.
In this case report, the complexity of the clinical presentations in CVID patients was stressed. The considerable point was a mismatch primary clinical diagnosis of FAP, due to prominent polyp-like endoscopic appearance of the lesions throughout the digestive tract; though no dysplasia or adenomatous polyp was present. The large lymphopid follicles in the lamina propria of gut mucosa caused polypoid appearance leading to misdiagnosis.
|1||Rebecca H. Buckley. Immunology. In: Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson, Bonita F. Stanton. Nelson Textbook of pediatrics. 18th ed. Philadelphia: WB Saunders; 2007. p. 880.|
|2||Cunningham-Rundles C, Bodian C. Common Variable Immunodeficiency: Clinical and Immunological Features of 248 Patients. Clin Immunol 1999;92:34-48.|
|3||Hogenauer CH, Hammer HF. Maldigestion and malabsorption. In: Feldman M, Friedman LS, Sleisenger MH, editors. Gastrointestinal and Liver Diseases. Philadelphia: WB Saunders; 2002. p. 1775.|
|4||Eibl MM, Wolf HM. Common variable immunodeficiency: clinical aspects and recent progress in identifying the immunological defect(s). Folia Microbiol (Praha) 1995;40:360-6. |
|5||Cooper MD, Schroeder HW. Primary immune deficiency. In: Kasper DL, Braunwald E, Fauci A, Hauser S, Longo D, Jameson L, editors. Harrison's principles of internal medicine. 16th ed. New York: McGraw-Hill; 2004. p. 1944.|
|6||Washington K, Stenzel TT, Buckley RH, Gottfried MR. Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia. Am J Surg Pathol 1996;20:1240-52.|
|7||Hermaszewski RA, Webster AD. Primary hypogammaglobulinemia: A survey of clinical manifestations and complications. Q J Med 1993;86:31-42.|
|8||Aghamohammadi A, Farhoudi A, Moin M, Pourpak Z, Rezaei N, Abolmaali K, et al. A single-center 20-year survey of infectious complication in 64 patients with common variable immunodeficiency. Med J IR Iran 2002;16:123-8.|
|9||Ebrahimi Daryani N, Aghamohammadi A, Mousavi Mirkala MR, Bashashati M, Rezaei N, Haghpanah B, et al. Gastrointestinal Complications in Two Patients with Common Variable Immunodeficiency. Iran J Allergy Asthma Immunol 2004;3:149-152 |
|10||Lai Ping So A, Mayer L. Gastrointestinal manifestations of primary immunodeficiency disorders. Semin Gastrointest Dis 1997;8:22-32.|