|Year : 2013 | Volume
| Issue : 4 | Page : 455-458
Squamous cell carcinoma of gall bladder: A rare case
Pasula Jijiya Bai, Shyamala Srujana, Syed Sajjad Saifullah Quadri, Neelam Sreemani Kumari
Department of Pathology, Gandhi Medical College, Secunderabad, India
|Date of Web Publication||17-Sep-2013|
Pasula Jijiya Bai
Department of Pathology, Gandhi Medical College, Secunderabad, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
A 55-year-old female patient presented with pain in upper-right abdomen region since 2 months, associated with vomiting and fever. USG abdomen revealed well-distended gall bladder with multiple small calculi along with large hyperechoic area sludge. A provisional diagnosis of Empyema of gall bladder with cholelithiasis was considered. Laparoscopic cholecystectomy was done. The histopathological findings were suggestive of infiltrating well-differentiated keratinizing squamous cell carcinoma of the gall bladder. Subsequently, diagnosis was confirmed by means of IHC studies.
Keywords: Cholelithiasis, gall bladder, squamous cell carcinoma
|How to cite this article:|
Bai PJ, Srujana S, Quadri SS, Kumari NS. Squamous cell carcinoma of gall bladder: A rare case. Med J DY Patil Univ 2013;6:455-8
| Introduction|| |
Gall bladder carcinomas are uncommon malignancies, being the fifth most common cancer of the digestive tract. It accounts for only 2% to 4% of all gastrointestinal malignancies.  The vast majority of masses found in the gall bladder are pathologically diagnosed as adenocarcinoma. Squamous cell carcinoma being even rare, constitute only 0-12.7% of gall bladder tumors. Pure squamous cell carcinoma of gall bladder is even less common with a reported incidence of 3.3%.
We report a single case of squamous cell carcinoma of gall bladder that was clinically diagnosed as Calculus cholecystitis with sludge Empyema of gall bladder.
| Case Report|| |
A 55-year-old female presented at the out patient clinic of surgery with complaints of pain in right hypochondrium for 2 months. It was associated with vomiting and fever. Her past medical and family histories were noncontributory. Physical examination revealed the presence of icterus and tenderness in right hypochondrium. No organomegaly was observed. Pulse rate and Blood Pressure were normal. Routine blood tests such as Complete Blood Picture, Random Blood Sugar, Blood Urea Nitrogen and serum creatinine were within normal limits. Liver Function Tests showed elevated serum bilirubin of 6 mg/dl with normal alkaline phosphatase levels.
USG abdomen revealed distended gall bladder with the wall thickness of 6 mm and of a large hyperechoic mass measuring 4 × 2 cm in the gall bladder sludge. On this basis, a clinical diagnosis of Calculus cholecystitis with sludge Empyema of gall bladder was considered, and admitted for surgery. Operative findings were suggestive of cholilithiasis of gall bladder with a friable mass, with adhesions to the omentum, possibly carcinoma. No obvious involvement of hepatic flexure, common bile duct, and extra hepatic biliary tree was observed.
Cholecystectomy was performed with release of adhesions. Pathologic evaluation revealed well-differentiated squamous cell carcinoma of gall bladder confined to wall. Postoperative period was uneventful.
Macroscopic findings: received cholecystectomy specimen already cut opened, measuring 6 × 3 cm with wall thickness of 6 mm. Lumen showed friable mass measuring 4 × 2 cm with multiple yellow colored cholesterol stones [Figure 1]. Multiple bits were given from representative areas and routinely processed.
|Figure 1: Gross Specimen: shows already cut opened gall bladder with a 4 × 2 cm irregular grey-white friable mass|
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Histopathological examination [Figure 2], [Figure 3], [Figure 4] revealed native gall bladder tissue with mucosa lined by columnar epithelium with an abrupt transition to tumor, which is seen infiltrating into the muscle layer up to the serosa. Tumor was arranged in diffuse sheets, solid aggregates. Individual neoplastic cells were large round to polygonal having distinct cell borders, abundant eosinophilic cytoplasm, and pleomorphic hyperchromatic nucleus. Some of the cells showed prominent nucleoli. Occasional mitotic activity per high power field was noted along with chronic inflammatory cell infiltrate. Numerous keratin pearls were noted. Both PAS and Alcian Blue staining were negative. Mucin production, glandular structures were not detected even on serial tissue sections. Normal surrounding gall bladder mucosa showed features of chronic cholecystitis. Metaplastic squamous epithelium or heterotopic squamous epithelium were not observed in the sections studied. Sections from external surface showing adherence to omentum did not reveal any tumor infiltration.
A provisional diagnosis of infiltrating well-differentiated keratinizing squamous cell carcinoma of gall bladder was made. On immunohistochemistry, the gall bladder tumor was positive for HMW cytokeratins, confirming the diagnosis of squamous cell carcinomas of the gall bladder [Figure 5] and [Figure 6].
|Figure 3: H & E 10×: shows columnar lining epithelium of gall bladder (lower portion) with squamous cell carcinoma (upper portion)|
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|Figure 4: H & E 10×: shows infiltrating well differentiated keratinized squamous cell carcinoma of gall bladder|
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| Discussion|| |
Squamous cell carcinoma of the gall bladder is an uncommon neoplasm, demonstrating considerable geographic and gender variation. It accounts for only 2% to 4% of all gastrointestinal malignancies  North India is one of the regions having highest incidence of gall bladder carcinoma. Other high incidence areas are reported in Latin America and Eastern Europe. It shows female preponderance with F: M ratio of 3-4: 1. It occurs in the elderly age group, seventh decade, while our patient was 55-year-old female.
It is a highly malignant neoplasm presenting at an advanced stage in majority of the cases. Surgery is the only treatment available, only when diagnosed at an early stage.
Etiology for squamous cell carcinoma in the gall bladder is not well defined. Epithelial tumor genesis is a multistep process resulting from sequential genetic alteration at different stages of evolution. Because a normal gall bladder has no squamous epithelium, the source of origin is questionable. The most plausible theory involves squamous metaplasia or squamous differentiation of adenocarcinoma. According to this hypothesis, squamous cell carcinoma of gall bladder develops as follows. An initial pre-existing adenocarcinoma that undergoes squamous metaplasia to produce adenosquamous carcinoma and this metaplastic carcinoma subsequently grows rapidly and replaces the adenocarcinoma component to form pure squamous cell carcinoma.  In the present case squamous cell carcinoma infiltrated up to the subserosal layer from the mucosal surface and it was found not to contain either a part of an adenocarcinoma or the transitional cells of adenocarcinoma in conversion to squamous cell carcinoma. In addition, the tumor cells were negative for PAS and Alcian blue stain, neither a metaplastic squamous epithelium nor heterotopic squamous epithelium were observed in the surrounding gall bladder mucosa. Mucin production, glandular structures were not detected even on serial tissue sections. Therefore, in the present case squamous cell carcinoma appears to have histological features that differ from those in any of the proposed hypothesis. The concept of squamous cell carcinoma originating from preexisting metaplastic squamous epithelium appears unlikely, because this kind of metaplasia virtually does not exist even in non-neoplastic conditions of gall bladder including chronic cholecystitis and cholelithiasis. 
Gall stones appear to be a major risk factor in the carcinogenesis of carcinoma of any type but more so for squamous cell carcinoma. Approximately 90% of squamous cell carcinoma cases invariably have cholelithiasis.  A recent study of seven patients with squamous cell carcinoma of gall bladder is reported to have cholelithiasis, cholesterol type in all the seven cases.  Our case also revealed cholesterol gall stones.
Other pathologies that have been associated with increased risk of gall bladder carcinomas include polypoidal lesions, adenomas, calcified porcelain gall bladder, cholecysto-enterior enteric fistulae, ulcerative colitis, adenomyomatosis, polyposis coli and anomalous connection between CBD and pancreatic duct.
Genetic changes have also been identified along with mutations that consist of decreased expression of 23 nm and overexpression of c-erb B2 gene product. 
Surgery is the primary treatment. However, due to the diagnosis of lesion at an advanced stage, in most of the patients, surgery is not possible. This carcinoma is rarely detected at an early resectable stage. Differences between presentation of adenocarcinoma and squamous cell carcinoma are vague. Kumar et al.  claim that the pure squamous cell carcinoma is characterized by a well-localized growth with no lymph nodal or visceral metastasis, even with tumors of large size. Prognosis of squamous cell carcinoma is dismal with a mean 5-year survival rate of 1%. However, when combined with adenosquamous carcinoma, the squamous carcinoma cells seem to take an aggressive nature.
| Conclusion|| |
Knowledge of various types of gall bladder cancers and their precursor lesions can aid in understanding the behavior and treatment of both usual and unusual types of gall bladder cancers. Careful sonographic examination may help to decrease the mortality associated with this disease enabling early detection at an earlier stage.
| References|| |
|1.||Kumar V, Cotran RS, Robbins SL. Robbins basic pathology. 7 th ed, Philadelphia: WB Saunders; 2003. |
|2.||Roppongi T, Takeyoshi I, Ohwada S, Sato Y, Fujii T, Honma M, et al. Minute squamous cell carcinoma of gall bladder: A case report. Jpn J Clin Oncol 2003;30:43-5. |
|3.||Kumar A, Singh MK, Kapur BM. Synchronous double malignant tumors of the gall bladder: A case report of Squamous cell carcinoma and angiosarcoma. Eur J Surg Oncol 1994;20:63-7. |
|4.||Schwrtz SL, Shires E, Spencer FC, Daly JM, Fisher JE, Galloway AC. Principles of surgery. 7 th ed, New York: McGraw-Hill; 2006. |
|5.||Cariati A, Francesco C. Squamous cell carcinoma and non-squamous cell carcinoma of gall bladder have different risk factors. Lancet Oncol 2003;4:393-4. |
|6.||Rhodes PS, BS. Gallbladder Carcinoma with the unusual occurrence of squamous cell carcinoma: A case study. J Diagn Med Sonography 2004;20:347-50. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 6], [Figure 6]