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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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Dysplasia in RAS and adenomyosis can mimic invasive GBC. A-B: Dysplastic epithelium within RAS penetrating slightly beyond the wall, C: dysplastic epithelium associated with adenomyosis, D: Foci of intramural invasive carcinoma (H&E stain).
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Figure 2: Dysplasia in RAS and adenomyosis can mimic invasive GBC. A-B: Dysplastic epithelium within RAS penetrating slightly beyond the wall, C: dysplastic epithelium associated with adenomyosis, D: Foci of intramural invasive carcinoma (H&E stain).

Mentions: Another potential problem area that should be considered is carcinoma arising from RAS, without tumor mass [3]. We believe this is extremely rare, although conceivably more advanced cancers could have arisen from such a location. Demonstration of this requires a minute adenocarcinoma arising from RAS and located in the wall or subserosa, with no apparent connection to mucosa as in case E above (See Table 2) of a 45-year-old woman with preoperative diagnosis of cholelithiasis. The morphological diagnosis at another hospital was transmurally invasive moderately differentiated adenocarcinoma, though no mass was identifiable grossly and the wall only focally thickened to 5 mm. Subsequent review of the previously removed gallbladder revealed extensive surface dysplasia, with high grade dysplastic epithelium within RAS penetrating slightly beyond the wall (See Figure 2A) and foci of intramural invasive carcinoma (See Figure 2B). The gradual transition between adenocarcinoma cells and RAS with dysplasia was recognized. A key differentiating feature from adenomyosis is that muscular hypertrophy was not pronounced. Cytologic atypia sufficient for a diagnosis of adenocarcinoma should also be evident. In general, carcinoma arising from RAS is small and has a relatively good prognosis. Therefore, careful examination of resected gallbladders is necessary [6], particularly any areas of focal mural thickening.


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)

Dysplasia in RAS and adenomyosis can mimic invasive GBC. A-B: Dysplastic epithelium within RAS penetrating slightly beyond the wall, C: dysplastic epithelium associated with adenomyosis, D: Foci of intramural invasive carcinoma (H&E stain).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Dysplasia in RAS and adenomyosis can mimic invasive GBC. A-B: Dysplastic epithelium within RAS penetrating slightly beyond the wall, C: dysplastic epithelium associated with adenomyosis, D: Foci of intramural invasive carcinoma (H&E stain).
Mentions: Another potential problem area that should be considered is carcinoma arising from RAS, without tumor mass [3]. We believe this is extremely rare, although conceivably more advanced cancers could have arisen from such a location. Demonstration of this requires a minute adenocarcinoma arising from RAS and located in the wall or subserosa, with no apparent connection to mucosa as in case E above (See Table 2) of a 45-year-old woman with preoperative diagnosis of cholelithiasis. The morphological diagnosis at another hospital was transmurally invasive moderately differentiated adenocarcinoma, though no mass was identifiable grossly and the wall only focally thickened to 5 mm. Subsequent review of the previously removed gallbladder revealed extensive surface dysplasia, with high grade dysplastic epithelium within RAS penetrating slightly beyond the wall (See Figure 2A) and foci of intramural invasive carcinoma (See Figure 2B). The gradual transition between adenocarcinoma cells and RAS with dysplasia was recognized. A key differentiating feature from adenomyosis is that muscular hypertrophy was not pronounced. Cytologic atypia sufficient for a diagnosis of adenocarcinoma should also be evident. In general, carcinoma arising from RAS is small and has a relatively good prognosis. Therefore, careful examination of resected gallbladders is necessary [6], particularly any areas of focal mural thickening.

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