|Year : 2014 | Volume
| Issue : 3 | Page : 749-751
Gall bladder lymphoid hyperplasia: Masquerading as lymphoma
Safia Rana, Zeeba S Jairajpuri, Sabina Khan, Mohammed Jaseem Hassan, Sujata Jetley
Department of Pathology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, Hamdard Nagar, New Delhi, India
|Date of Web Publication||14-Oct-2014|
Dr. Sujata Jetley
Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi - 110 062
Source of Support: None, Conflict of Interest: None
Lymphoid hyperplasia of the gall bladder is an extremely rare condition that may be missed on associated radiological or clinical evaluation but is diagnosed on biopsy. We are reporting hereby, a case of reactive lymphoid hyperplasia masquerading as a lymphoma on histopathology. A 58-year-old male was referred to our hospital with complaints of pain abdomen infrequently since last one year. Ultrasonography revealed the presence of single calculus along with features of chronic cholecystitis. Laparoscopic cholecystectomy was performed and the gall bladder was sent for routine histopathological evaluation. On microscopic examination, there were sheets of cells, lymphoid in origin and numerous lymphoid follicles spread throughout the wall of the gall bladder. It was diagnosed as a case of reactive lymphoid hyperplasia with chronic cholecystitis on histopathology.
Keywords: Gall bladder, lymphoid hyperplasia, lymphoma
|How to cite this article:|
Rana S, Jairajpuri ZS, Khan S, Hassan MJ, Jetley S. Gall bladder lymphoid hyperplasia: Masquerading as lymphoma. J Can Res Ther 2014;10:749-51
| > Introduction|| |
Lymphoid hyperplasia of the gall bladder is a rare, benign lesion diagnosed microscopically as hyperplastic lymphoid follicles with germinal centers.  It may arise from various organs like lungs, gastrointestinal tract, orbit and skin. , Lymphoid hyperplasia of the gall bladder is an extremely rare entity, usually presenting as granular or polypoidal lesion of the mucosa. The pathogenic basis is thought to be either autoimmune mechanism or continuous inflammation, however the exact cause has not been identified.  Lymphoid hyperplasia of the gall bladder following the chronic cholecystitis has been reported previously.  We report here a case of 58-years-old male, preoperatively diagnosed as a case of gallstone disease, revealing reactive lymphoid hyperplasia of the gall bladder on histopathological examination.
| > Case Report|| |
A 58-year-old male presented to the surgery outpatient department with pain in the right upper quadrant infrequently, associated with nausea and vomiting for the last one year. There was no history of fever, jaundice or pruritus and no past relevant medical history. Physical examination showed absence of pallor, icterus or any palpable lymph nodes. Right upper quadrant was tender with a positive Murphy's sign. No rebound tenderness was present. A complete clinical workup of the patient was done. Laboratory investigations revealed serum bilirubin (1.1 mg/dl); direct (0.6 mg/dl); alkaline phosphatase 208 IU/L; ALT 64IU/L. Other biochemical tests like serum lipase, serum electrolytes were within normal limits.
Hematological parameters were - hemoglobin of 12.2 g/dl with a normal blood count, except mild leukocytosis (WBC count 11,300 cells/μL). Ultrasound of the upper abdomen showed a thickened gall bladder wall with Single calculus and a diagnosis of chronic cholecystitis with cholelithiasis was made. The patient underwent a laparoscopic cholecystectomy and symptomatic gallstone disease was the indication for this surgery. On gross examination, the gall bladder measured 7.2 × 3 cm with wall thickness varying from 0.8-1 cm. Solitary brown to black calculi was seen in the lumen of neck region [Figure 1].
|Figure 1: Gross photograph of gall bladder with solitary stone present within the lumen|
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On microscopic examination, hematoxylin and eosin (H and E) stained sections of the gall bladder showed diffuse infiltration of the wall by sheets of monotonous appearing cells of lymphoid origin. Numerous lymphoid follicles with germinal centers were also seen. Few large cells with irregular nuclei, prominent nucleoli and minimal cytoplasm were present. Occasional mitotic figures were seen in the background. The overlying mucosal lining epithelium did not show any abnormality [Figure 2] and [Figure 3]. A provisional impression of lymphoproliferative lesion was made. Keeping this in mind, immunohistochemistry (IHC) was advised. However, due to nonavailability of IHC at our center the case was referred to an outside lab. The IHC profile, CD20, Bcl-2, CD5, CyclinD1 and CD23 was consistent with reactive change. Therefore, ruling out lymphoproliferative lesions like follicular lymphoma, Mantle cell lymphoma and MALT lymphoma. A combined histopathological and IHC diagnosis of reactive follicular hyperplasia of the gall bladder with chronic cholecystitis was finally achieved.
|Figure 2: Microphotograph showing mucosal lining epithelium and diffuse infiltration of the wall by sheets of monotonous appearing cells of lymphoid origin. (H and E, ×20)|
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|Figure 3: Microphotograph showing lymphoid follicles with germinal centers. (H and E, ×20)|
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| > Discussion|| |
Lymphoid hyperplasia of the gall bladder is an extremely rare and benign entity characterized by hyperplastic lymphoid follicles with germinal centers consisting of polymorphous lymphoid population.  This condition also occurs in lungs, orbit, skin and GIT. , It has been mentioned in literature that lymphoid hyperplasia, pseudolymphoma and follicular cholecystitis are some of the terms which describe the same lesion of the gall bladder. 
Lymphoid tissue in normal mucosa of the gall bladder is very sparse and lymphoid follicles are not seen. However, some intraepithelial lymphocytes are evident among the surface columnar epithelial cells.  Reactive lymphoid hyperplasia is considered to occur either as a result of long standing inflammation or due to an autoimmune mechanism.  Reactive lymphoid hyperplasia of the gall bladder may arise after chronic cholecystitis as was noted in the present case.  Association with a malignant tumor may also be present. , However, the exact cause of lymphoid hyperplasia has not yet been identified.
Most commonly, the middle aged or elderly females are affected and they suffer from various chronic inflammatory conditions like chronic hepatitis, thyroiditis or primary biliary cirrhosis. However, the present case was a middle aged male. Laparoscopic cholecystectomy is the first therapeutic modality and the final diagnosis rests on the histopathological diagnosis of the resected biopsy. Review of previous literature has shown cases with uneventful post-operative period without any recurrences after the surgery. 
Malignant lymphoma is an important differential diagnosis of reactive lymphoid hyperplasia and is always a possibility to be kept in mind. Although lymphomas are thought to be primarily tumors of lymph nodes, a substantial proportion arises from other tissues. The most common lymphomas masquerading as cholecystitis are mucosa associated lymphoid tissue (MALT) lymphoma, follicular lymphoma, mantle cell lymphoma and CLL/SLL. 
The primary MALT lymphoma of the gall bladder is characterized by diffuse infiltration of cells resembling the small cleaved follicular cells and many plasma cells along with epithelial invasion by lymphoma cells thus differentiating it from reactive change.  MALT lymphoma represent 38% of all the previously reported primary GB lymphoma thus accounting for the most frequent NHL of the gall bladder. The prognosis after cholecystectomy is excellent if the lesion is localized in the gall bladder. , The lymphoid cells are strongly positive for CD20, CD79a, CD43 and Bcl-2.
In follicular lymphoma (FL), the follicles are uniform in size, without a well formed mantle zone with a monomorphous cell population. However, in contrast, the reactive follicles are of variable size with a distinct mantle zone, and a polymorphous lymphoid population, as seen in our case. IHC detection of bcl-2 oncoproteins show diffuse and intense positivity in FL, while the normal germinal centers lack bcl-2 positivity with less prominence in mantle zone, and interfollicular cells. , Proliferative activity assessed by measuring Ki-67 also contributes in discriminating between FL and reactive hyperplasia, can vary from 0.5%-59% (mean 15.6%). 
Mantle cell lymphoma consists of small to medium sized centrocytic cells, exhibiting CD5 and cyclin D1 positivity, and also bcl-2 expression. Chronic lymphocytic leukemia (CLL) with GB involvement is extremely rare, only few cases of CLL infiltrating GB wall or biliary tree have been reported.  On histology, a monotonous population of small monoclonal lymphoid cells infiltrating the GB wall is seen hence, CLL is also a diagnostic possibility. IHC shows strong positivity for bcl-2, CD 5, CD23, CD43 and PAX 5.  However, our case was negative for CD5 and bcl-2 markers.
| > Conclusion|| |
We conclude that lymphoid hyperplasia of the gall bladder is a benign and extremely rare entity often masquerading as lymphoma on morphology. Malignant lymphoma must be excluded when a case of lymphoid hyperplasia is encountered. IHC staining is necessary to confirm the diagnosis in conjunction with morphology. In the majority of cases where the lesion is localized to the GB, cholecystectomy alone is considered curative and prognosis is excellent.
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[Figure 1], [Figure 2], [Figure 3]