A case of pure endophytic squamous cell carcinoma of the gallbladder: a rare entity with aggressive behaviour

Pure squamous cell carcinoma of gallbladder is a rare tumor accounting for only 3% of the malignancies of gallbladder. A 35-year-old female presented with pain and lump in right hypochondrium. Ultrasonography and computed tomography revealed a thickened gallbladder filled with stones without any obvious growth and a large hepatic mass. Histologically, a pure type of well differentiated squamous cell carcinoma of gallbladder was diagnosed after excluding all possible differential diagnoses owing to different histogenesis and aggressive biological behaviour. Early diagnosis is the most important parameter for improving the survival indices among the patients with squamous cell carcinoma of the gallbladder.     

A case of hemorrhagic gallbladder paraganglioma causing acute cholecystitis.

Gallbladder paraganglioma is a very rare tumor and so far only a few cases have been reported. Most of these were asymptomatic and were found incidentally during operation. Recently, we experienced a gallbladder paraganglioma that gave rise to hemorrhage, which in turn caused acute cholecystitis. Our case involved a 45 year-old female patient complaining of an intermittent right upper abdominal pain. After a preoperative evaluation, cholecystectomy and lymphadenectomy were performed under the impression of gallbladder cancer with acute cholecystitis. Postoperative pathologic examination revealed a hemorrhagic gallbladder paraganglioma accompanied by acute cholecystitis. Immunohistochemical staining of the chief cells for neuron specific enolase, chromogranin and synaptophysin were positive. Sustentacular cells also stained positively for S100 protein.     

It's the Bloody Gallbladder! Spontaneous Gallbladder Hemorrhage Following Factor Xa Inhibition

Spontaneous gallbladder hemorrhage (SGBH) is a rare diagnosis related to trauma, malignancy or vascular abnormalities, associated with significant morbidity and mortality. We present a case of SGBH in a 55-year-old patient with right upper quadrant (RUQ) pain following initiation of apixaban for deep vein thrombosis post recent kidney transplant. Multiple imaging studies revealed a distended gallbladder with heterogeneous hyperdense material in the lumen and cystic duct obstruction. Surgery revealed a gallbladder with chronic cholecystitis, hemorrhage and hematoma. This case highlights a rare adverse event of anticoagulation, and SGBH should be considered when acute RUQ pain occurs in this setting.     

Acalculus lymphoeosinophilic cholecystitis associated with interleukin-2 and lymphokine-activated killer cell therapy

A case of unusual cholecystitis that developed on completion of interleukin-2 and lymphokine-activated killer cell therapy is described. A 62-year-old man was treated with interleukin-2 and lymphokine-activated killer cells for disseminated renal cell carcinoma. During the course of the immunotherapy, his serum alkaline phosphatase level increased, as did the peripheral eosinophil count (0.31). Subsequently, clinical and radiologic evidence of acute cholecystitis was noted. The removed gallbladder showed acalculus cholecystitis with extensive diffuse infiltrates of numerous eosinophils and T lymphocytes, but sparse polymorphonuclear leukocytes. The authors name this unusual cholecystitis acalculus lymphoeosinophilic cholecystitis and believe it to be associated with interleukin-2 and lymphokine-activated killer cell therapy. The pathogenic relationship is discussed.     

A case of xanthogranulomatous cholecystitis preoperatively diagnosed with contrast-enhanced ultrasonography

We report a case of xanthogranulomatous cholecystitis (XGC) that was diagnosed preoperatively by means of ultrasonography (US) with the contrast-enhancement agent Sonazoid after a false-positive result had been obtained with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). A 69-year-old woman was admitted because of right upper quadrant pain. Blood tests revealed a serum CA19-9 level of 749.8 IU/L. Computed tomography (CT), US, and magnetic resonance imaging of the abdomen showed abnormal thickening of the gallbladder wall but no stones. The border between the gallbladder and the liver was unclear. FDG-PET revealed a lesion with increased uptake of tracer in the gallbladder wall. The thickness of the lesion was similar to that on CT. We suspected gallbladder carcinoma with hepatic invasion. To confirm the tentative diagnosis, we performed US with the contrast-enhancement agent Sonazoid. The gallbladder wall was homogeneously enhanced in the early vascular phase and remained enhanced for 90 seconds. Enhancement of the gallbladder wall was smooth and regular. The border between the gallbladder and liver was clear and smooth. On the basis of these examinations, we diagnosed chronic cholecystitis (XGC suspected), not gallbladder carcinoma. At surgery, the gallbladder wall was observed to be extremely thick because of severe inflammation, and cholecystectomy was performed. XGC was diagnosed on intraoperative pathological examination. Histopathological examination showed XGC, severe proliferative fibrosis with formation of multiple yellow-brown intramural nodules, and foamy histiocytes without malignant cells. In conclusion, the present case of XGC was diagnosed preoperatively with contrast-enhanced US after a false-positive result had been obtained with FDG-PET. Contrast-enhanced US can thus play important roles in diagnosing gallbladder disease and selecting treatment.     

Neutrophilic inflammation in gallbladder carcinoma correlates with patient survival: A case-control study

Gallbladder carcinoma is an uncommon malignancy with an overall 5-year survival of less than 5%. Gallbladder carcinoma has been strongly linked with cholelithiasis and chronic inflammation. Case reports and series have described cholecystitis with acute (neutrophilic) inflammation in association with gallbladder carcinoma, although a clear relationship to patient outcome has not been established. Our series included 8 cases of gallbladder carcinoma with high tumor-associated neutrophils (>25 per high power field) that were associated with shorter patient survival (Cox regression coefficient 6.2, p = 0.004) than age- and stage-matched controls. High tumor-associated neutrophils were not associated with gallbladder rupture/perforation or increased bacterial load measured by 16S PCR. Neutrophilic inflammation with gallbladder carcinoma correlates to shorter survival, independent of patient age and stage of carcinoma. The findings suggest that the degree of neutrophilic inflammation may have prognostic significance in specimens from patients with gallbladder carcinoma after cholecystectomy. Further studies with larger case numbers are needed to confirm and generalize these findings.     

Squamous cell carcinoma of the gallbladder associated with squamous metaplasia and adenocarcinoma in situ of the mucosal columnar epithelium

A case of well-differentiated squamous cell carcinoma of the gallbladder is presented. Unlike most previously reported cases, the tumor developed in association with squamous metaplasia as well as dysplastic and in situ adenocarcinomatous changes of the gallbladder epithelium. The significance of these lesions is discussed in relation to the histogenesis of squamous cell carcinoma or adenosquamous carcinoma of this organ.     

SQUAMOUS CELL CARCINOMA OF THE GALLBLADDER ASSOCIATED WITH SQUAMOUS METAPLASIA AND ADENOCARCINOMA IN SITU OF THE MUCOSAL COLUMNAR EPITHELIUM

A case of well-differentiated squamous cell carcinoma of the gallbladder is presented. Unlike most previously reported cases, the tumor developed in association with squamous metaplasia as well as dysplastic and in situ adenocarcinomatous changes of the gallbladder epithelium. The significance of these lesions is discussed in relation to the histogenesis of squamous cell carcinoma or adenosquamous carcinoma of this organ.     

Intravascular large B-cell lymphoma manifesting as cholecystitis: report of an Asian variant showing gain of chromosome 18 with concurrent deletion of chromosome 6q

Intravascular large B-cell lymphoma (IVLBCL), which involves the lumen of small vessels, is a rare variant of extranodal diffuse large B-cell lymphomas. Herein, we present a case of IVLBCL manifesting as cholecystitis in a 77-year-old Japanese man. He presented with fever, fatigue, and weight loss. Physical examination revealed tenderness of the right upper quadrant. The white blood cell count and C-reactive protein levels were elevated. Computed tomography revealed gallbladder thickening and pericholecystic fluid collection; these observations were consistent with the diagnosis of cholecystitis. Serum soluble interleukin-2 receptor levels were highly elevated, and gallium scintigraphy revealed an abnormal accumulation in the spleen, implying lymphoma. Consequently, G-banding analysis of the patient’s bone marrow aspirates revealed the presence of different abnormal clones, including those with gain of chromosome 18 and deletion of chromosome 6q. As cholecystectomy was necessary, a concurrent splenectomy was performed to diagnose the disease definitively. Histopathologically, atypical large lymphoid cells were observed to be localized in the vasculature in both the spleen and gallbladder; the atypical cells expressed high levels of CD20, CD5, and CD10, immunohistochemically. These findings were consistent with IVLBCL. The patient underwent post-operative treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone. However, a pancreatic fistula developed during chemotherapy, causing left pleural effusion and peritoneal effusion; the patient developed sepsis from multidrug-resistant microorganisms, and subsequently died of multi-organ failure 6 months after the diagnosis. No obvious recurrence of the tumor was found during autopsy. We discuss the characteristic karyotype and immunohistochemical status observed in this case.     

Mixed adenoneuroendocrine carcinoma of the gallbladder with squamous cell carcinomatous and osteosarcomatous differentiation: Report of a case

An extremely rare case of mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder is reported, in which the tumor showed diverse differentiation toward neuroendocrine tumor (grade 2), tubular adenocarcinoma, squamous cell carcinoma, and, in addition, osteosarcoma. The patient was an 80‐year‐old man, who underwent cholecystectomy because of a large polypoid tumor filling the gallbladder lumen. The tumor consisted of an intimate admixture of neuroendocrine tumor (grade 2) and tubular adenocarcinoma, and, in many areas, cell nests of neuroendocrine tumor appeared to bud off from tubular structures of the adenocarcinoma, in a manner resembling the ‘ductulo‐insular complex’ seen in nesidioblastosis of the pancreas. Small areas of squamous cell carcinoma were also found. The stroma consisted of a dense proliferation of atypical spindle cells showing focal osteosarcomatous differentiation, and an apparent transition from an epithelial tissue component to atypical spindle cells was observed. Immunohistochemically, neuroendocrine cells were positive for synaptophysin, chromogranin A, and serotonin, and the sarcomatoid stroma was partly immunoreactive for cytokeratin. The present case is the first example of MANEC of the gallbladder with simultaneous squamous cell carcinomatous and osteosarcomatous differentiation. ‘Neometaplasia’ of carcinoma cells in diverse directions was considered the most plausible explanation for the formation of this multifaceted neoplasm.     

Gallbladder carcinoma in the "Hospital de Clinicas" of Uruguay: 1998-2002. A clinicopathologic study of five cases in 802 cholecystectomies

Five cases of primary carcinoma of the gallbladder are presented. The cases were identified after a study of 802 cholecystectomies in a period of 5 years. The patients are three women and two men between the ages of 43 and 60 years (mean, 55.8 years). In three cases the clinical diagnosis was that of carcinoma, while in two other patients the clinical diagnosis was that of acute cholecystitis. Grossly, all cases were characterized by a gray-white diffuse or focal plaque-like thickening of the gallbladder wall, with loss of the normal velvety mucosal surface and fibrosis of the organ. Histologically, four cases belong to moderately to poorly differentiated adenocarcinoma and were characterized by infiltrative, irregularly shaped and sized glands, islands, nests, and cords. The cells showed pleomorphic nuclei with clumped chromatin and frequent single nucleoli. One case was a mucinous adenocarcinoma characterized by large pools of mucoid material with neoplastic glands and cells "floating" within. Pathologic staging was pT3 in three cases; pT2 in one case; and pT2N1 in one other case. The present study highlights the importance of careful gross and histopathologic evaluation of gallbladders otherwise removed with the history of chronic or acute cholecystitis. In addition, it highlights the incidence of gallbladder carcinoma in a particular institution.     

Small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone.

We report a case of primary small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone, which is unique in that the patient has remained free of tumor recurrence for 36 months after the surgery without adjuvant chemotherapy or radiotherapy. A 60-yr-old man presented himself with a right flank pain. Computed tomography revealed an ill-defined mass and a stone in the lower one third of the right ureter, and hydronephroureterosis above the stone-impacted site. The patient underwent right nephroureterectomy and stone removal. Upon gross examination, a 3.8 x 1.8 x 1.2 cm white and partly yellow mass was noted in the anterior part of the ureter, resulting in indentation of the ureteral lumen on the posterior side. Light microscopic examination revealed that the mass was mainly composed of small cell carcinoma, and partly squamous cell and transitional cell carcinomatous components. The overlying ureteral mucosa and renal pelvis also contained multifocal dysplastic transitional epithelium and transitional cell carcinoma in situ. There was no vascular invasion, and the surgical margins were free of tumor. The small cell carcinomatous component was positive for chromogranin, neuron specific enolase, synaptophysin, and pancytokeratin but negative for high molecular-weight cytokeratin (K-903) by immunohistochemistry.     

Enhanced cell kinetics, p53 accumulation and high p21WAF1 expression in chronic cholecystitis: comparison with background mucosa of gallbladder carcinomas

AIMS: Since neoplasia resulting from chronic inflammation has recently attracted increasing attention, we have investigated surgically removed gallbladders to examine the relationship between chronic cholecystitis and carcinogenesis. METHODS AND RESULTS: The mucosa of 108 cholecystectomy specimens without gallbladder cancer and 54 surgically resected gallbladder carcinomas were classified into three groups according to the degree of lymphocytic infiltration, and assessed immunohistochemically for Ki67, p53, p21WAF1 and apoptosis. In gallbladder mucosa without carcinoma, all four parameters tended to increase with the inflammation score (IS). Significantly positive correlations were revealed between Ki67 and p53, Ki67 and p21WAF1, and p53 and p21WAF1. However, in gallbladder carcinoma cases, values of p53 and p21WAF1 for background mucosa were elevated as compared to the mucosa of cholecystitis with low IS, but there was no correlation between their expression and IS, except for Ki67. CONCLUSIONS: Severe chronic cholecystitis is associated with acceleration of epithelial cell turnover, damaged cells being eliminated by apoptosis. The background mucosa of gallbladder carcinomas showed similar cell proliferative activity (Ki67) to that in cholecystitis, with no parallel changes of p53 and p21WAF1 expression, suggesting the possibility of unknown cofactors causing genomic damage.     

Hepatoid carcinoma of the gallbladder

Hepatoid carcinoma is a special type of extrahepatic tumor associated with hepatic differentiation, and has the morphological and functional features of hepatocellular carcinoma. Hepatoid carcinoma of the gallbladder is very rarely reported in the literature. We report a case of hepatoid carcinoma of the gallbladder in a 71-year-old female who presented with abdominal pain and was first diagnosed as cholelithiasis with cholecystitis. The microscopic findings of the gallbladder after cholecystectomy showed an area of tumor with polygonal cells, eosinophilic cytoplasm, distinct cell borders, round vesicular nuclei and prominent nucleoli, arranged in trabecular pattern resembling hepatocellular carcinoma intermingled with areas of adenocarcinoma or cholangiocarcinoma. The specimen from the pancreas also showed the same type of tumor cells. Histochemically, some of tumor cells were positive for Victoria Blue, Stein, and PAS. The immunohistochemistry for alpha-fetoprotein (AFP) showed strong intra cytoplasmic positivity, both in tumor cells with hepatic differentiation and tumor cells with bile duct epithelium differentiation. Based on these findings, this case was diagnosed as hepatoid carcinoma of the gallbladder with metastasis to the pancreas. This is the first case that has been reported in our department.     

SQUAMOUS CELL CARCINOMA OF GALLBLADDER

Two cases of a well-differentiated keratinizing squamous cell carcinoma of the gallbladder were reported. Pathologic analysis of this rare neoplasm was made in conjunction with cases of the gallbladder carcinoma of a squamous cell variety reported in literatures. The squamous cell carcinoma is characterized by a well-localized growth and a rarity or lack of metastasis. These characteristics make a good contrast with an adenosquamous carcinoma of the gallbladder which usually infiltrates rather extensively and metastasizes widely. Thus the adenosquamous carcinoma should be sequestered from group of squamous cell carcinoma. Radical operative procedures may well be encouraged on selected cases of squamous cell carcinoma.     

The effect of bactibilia on the course and outcome of laparoscopic cholecystectomy

Although bactibilia is an important condition of acute cholecystitis, its effect on the course and outcome of the infectious gallbladder disease has rarely been studied, particularly in relation to the laparoscopic procedure. The current study attempts to learn more about the inter-relationship between bactibilia and laparoscopic cholecystectomy during acute cholecystitis. Demographic, preoperative, operative, and postoperative data were prospectively collected in every patient with acute cholecystitis treated in the department of surgery at the Bnai Zion Medical Center, Israel. Intraoperative biliary samples were collected under aseptic conditions at the time of operation for bacteriologic examination and were routinely cultured in aerobic and anaerobic media for 3 days. The study population was divided into culture-positive and culture-negative groups, and the collected parameters were compared between the groups. Age over 60 years, a palpable gallbladder, temperature over 37.5 degrees C, a white blood cell (WBC) count of more than 12,000/cc(3), and serum alkaline phosphatase higher than 100 U/dL were all found to be factors capable of predicting bactibilia. Bactibilia was a significant factor associated with total, as well as infectious, operative complications. Bactibilia is considered to indicate an advanced stage of acute cholecystitis. In cases of laparoscopic cholecystectomy for infectious gallbladder disease, bactibilia is strongly associated with total, as well as local, infectious complications. Preoperative conditions such as older age, elevated temperature, a palpable gallbladder, elevated WBC count, and elevated serum levels of alkaline phosphatase can serve as predictors of bactibilia and its consequent complications. Although the sensitivity and specificity of the predictive factors for bactibilia are limited to 63% and 67%, respectively, in their presence during acute cholecystitis, conservative wide-spectrum antibiotics as the first-line therapy is appropriate, and, upon regimen failure, laparoscopic surgery by an experienced surgeon is indicated as the adjusted therapy.     

An elderly female with abdominal pain

A case of a 78-year-old female who presented with clinical, ultrasonographic and laboratory findings typical of acute cholecystitis is presented. Diagnostic laparoscopy revealed a hemorrhagic infrahepatic mass and free blood within the peritoneal space; the procedure was then converted to an open one, which identified a 15 x 5 cm mass corresponding to a gallbladder volvulus. The final histopathologic study confirmed the diagnosis. A gallbladder volvulus should be suspected in elderly patients, particularly in those with a previous history of significant weight loss, who additionally present positive clinical and paraclinical data of acute cholecystitis. There are no still biochemical exams that may preoperatively identify patients at high risk for this infrequent abnormality.     

Lateral cervical cyst with unsuspected metastasis from an occult tonsillar carcinoma

Lateral cervical cysts containing squamous cell carcinoma is a diagnostic and therapeutic challenge for the clinician since they usually represent a cystic metastasis from an occult carcinoma. Various imaging modalities or even blind biopsies will help identify the primary tumour. If the primary tumour is identified, an appropriate treatment decision can be made that incorporates both the primary tumour and the cervical node. If the primary remains unidentified, the neck is treated with a modified or radical neck dissection, depending on the extent of metastatic disease, and radiation therapy is administered to Waldeyer's ring and both necks. We present in this paper, a case with a large cervical cyst where histology showed the presence of a poorly differentiated squamous cell carcinoma in the wall of the cyst. A diagnostic evaluation of the patient was negative. Blind biopsies of the right tonsil revealed occult squamous cell carcinoma. The patient was treated by combined chemo/radiotherapy and she is doing well nine months following excision of the mass. The relevant literature is briefly reviewed.     

Disseminated cytomegalovirus infection presenting with acalculous cholecystitis and acute pancreatitis

Disseminated cytomegalovirus (CMV) infection occurs predominantly in immunocompromised hosts. Symptomatic CMV cholecystitis and pancreatitis are quite rare, and, to our knowledge, there are no reports of these occurring simultaneously. We describe a patient with a history of chronic myelogenous leukemia (treated with chemotherapy) who presented with recurrent unexplained fevers and an acute abdomen. At surgery, cholecystitis and pancreatitis were found, and a cholecystectomy was performed. The patient developed disseminated intravascular coagulation, eventual sepsis, and multiorgan failure. At autopsy, widespread disseminated CMV infection was found, with CMV-associated foci of acute inflammation and necrosis in the pancreas and in the surgically resected gallbladder. A review of our autopsy files revealed only one renal transplant patient with CMV inclusions and chronic pancreatitis. No pancreatitis was seen in 27 patients with acquired immunodeficiency syndrome. Cytomegalovirus should be considered as a possible cause of pancreatitis and cholecystitis in immunocompromised patients.