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Carcinoma involving the gallbladder: a retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma.

Giang TH, Ngoc TT, Hassell LA - Diagn Pathol (2012)

Bottom Line: Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases.Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical.Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

ABSTRACT

Background: Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.

Methods: We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.

Results: These cases illustrate seven potential pitfalls which can be encountered. These include: 1) mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis), 2) misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis), 3) differentiating between primary NEC of gallbladder and metastasis, 4) confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5) confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6) undersampling early, grossly occult disease, and 7) misinterpreting extracellular mucin pools.

Conclusions: Clinical history and a high index of suspicion are prerequisite to detecting GBC. Detection of GBC at an early stage is difficult because the symptoms mimic benign gallbladder diseases. Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases. Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical. Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.

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Geographic necrosis can mask underlying GBC. A: Extensive geographic necrosis and prominent acute inflammation (H&E stain, X100), B: The tumor was characterized by vesicular nuclei, prominent nucleoli, and scant eosinophilic cytoplasm (H&E stain, X400).
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Figure 3: Geographic necrosis can mask underlying GBC. A: Extensive geographic necrosis and prominent acute inflammation (H&E stain, X100), B: The tumor was characterized by vesicular nuclei, prominent nucleoli, and scant eosinophilic cytoplasm (H&E stain, X400).

Mentions: Some important pathologic findings overlap in benign and malignant lesions and may contribute to possible confusion, such as necrosis or extracellular mucus. An acute cholecystitis with parietal necrosis can be confused with an aggressive neoplastic process. Similarly, extensive tumor necrosis with minimal residual viable tumor may mimic acute gangrenous cholecystitis. Almost all cellular detail is lost in necrosis and most immunoperoxidase stains either fail or give misleading, non-specific falsly positive results. The presence of associated clinical signs can be of value to make the diagnosis of carcinoma or acute cholecystitis. The characteristics of the histologic changes in acute cholecystitis such as edema, vascular congestion, hemorrhage, fibrin deposition in the adventitia and adjacent muscle should be noted. Mucosal and mural necrosis may be seen with neutrophils [4,9]. Likewise, thorough histologic sampling is critical in cases with extensive necrosis to reveal diagnostic viable tumor. Since necrosis can occur in acute cholecystitis or a malignant tumor, it is important to adequately sample the gallbladder, including areas without necrosis. This is illustrated by case C above, a case of an 86-year-old woman with preoperative diagnosis of acute suppurative cholecystitis with cholelithiasis. She underwent cholecystectomy. Although gross tumor was present, significant geographic necrosis was present with prominent acute, chronic, and xanthogranulomatous inflammation, and viable tumor was only present in a subset of the well-sampled tumor (See Figure 3).


Carcinoma involving the gallbladder: a retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma.

Giang TH, Ngoc TT, Hassell LA - Diagn Pathol (2012)

Geographic necrosis can mask underlying GBC. A: Extensive geographic necrosis and prominent acute inflammation (H&E stain, X100), B: The tumor was characterized by vesicular nuclei, prominent nucleoli, and scant eosinophilic cytoplasm (H&E stain, X400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285085&req=5

Figure 3: Geographic necrosis can mask underlying GBC. A: Extensive geographic necrosis and prominent acute inflammation (H&E stain, X100), B: The tumor was characterized by vesicular nuclei, prominent nucleoli, and scant eosinophilic cytoplasm (H&E stain, X400).
Mentions: Some important pathologic findings overlap in benign and malignant lesions and may contribute to possible confusion, such as necrosis or extracellular mucus. An acute cholecystitis with parietal necrosis can be confused with an aggressive neoplastic process. Similarly, extensive tumor necrosis with minimal residual viable tumor may mimic acute gangrenous cholecystitis. Almost all cellular detail is lost in necrosis and most immunoperoxidase stains either fail or give misleading, non-specific falsly positive results. The presence of associated clinical signs can be of value to make the diagnosis of carcinoma or acute cholecystitis. The characteristics of the histologic changes in acute cholecystitis such as edema, vascular congestion, hemorrhage, fibrin deposition in the adventitia and adjacent muscle should be noted. Mucosal and mural necrosis may be seen with neutrophils [4,9]. Likewise, thorough histologic sampling is critical in cases with extensive necrosis to reveal diagnostic viable tumor. Since necrosis can occur in acute cholecystitis or a malignant tumor, it is important to adequately sample the gallbladder, including areas without necrosis. This is illustrated by case C above, a case of an 86-year-old woman with preoperative diagnosis of acute suppurative cholecystitis with cholelithiasis. She underwent cholecystectomy. Although gross tumor was present, significant geographic necrosis was present with prominent acute, chronic, and xanthogranulomatous inflammation, and viable tumor was only present in a subset of the well-sampled tumor (See Figure 3).

Bottom Line: Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases.Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical.Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

ABSTRACT

Background: Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.

Methods: We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.

Results: These cases illustrate seven potential pitfalls which can be encountered. These include: 1) mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis), 2) misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis), 3) differentiating between primary NEC of gallbladder and metastasis, 4) confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5) confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6) undersampling early, grossly occult disease, and 7) misinterpreting extracellular mucin pools.

Conclusions: Clinical history and a high index of suspicion are prerequisite to detecting GBC. Detection of GBC at an early stage is difficult because the symptoms mimic benign gallbladder diseases. Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases. Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical. Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.

Show MeSH
Related in: MedlinePlus