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Squamous cell and adenosquamous carcinomas of ... - BPA Pathology

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<strong>Squamous</strong> <strong>cell</strong> <strong>carcinomas</strong> <strong>of</strong> the gallbladder<br />

JC Roa et al 1075<br />

Table 1 Comparison <strong>of</strong> (a) clinicopathological <strong>and</strong> (b) histopathological characteristics <strong>of</strong> squamous <strong>cell</strong>/<strong>adenosquamous</strong> <strong>carcinomas</strong><br />

<strong>and</strong> ordinary adeno<strong>carcinomas</strong> <strong>of</strong> the gallbladder<br />

(a)<br />

Adenosquamous carcinoma/<br />

squamous <strong>cell</strong> carcinoma (N ¼ 34)<br />

Gallbladder<br />

adenocarcinoma (N ¼ 572)<br />

P-value<br />

Mean age 65 64 0.59<br />

Female/male 3.8 3.8 N/A<br />

Mean tumor size (cm) 3.1 2.7 0.42<br />

Median tumor size (cm) 2.5 2.4 N/A<br />

pT3 (%) 68 49 0.03<br />

Mean survival (months) (range) 23 (1–112.5) 50 (1–160) 0.003<br />

Median survival (months) 4 12<br />

(b)<br />

(N ¼ 34) (N ¼ 50)<br />

Tumor giant <strong>cell</strong>s (%) 29 10 0.02<br />

Peritumoral eosinophils (%) 51 6 0.001<br />

Vascular invasion (%) 76 72 0.21<br />

Perineural invasion (%) 32 48 0.22<br />

For comparison <strong>of</strong> clinicopathologic parameters listed in table 1a, all 572 adeno<strong>carcinomas</strong> were used. For comparison <strong>of</strong> some histopathologic<br />

parameters that require more detailed analysis listed in table 1b, r<strong>and</strong>omly chosen stage per stage matched 50 adeno<strong>carcinomas</strong> were used.<br />

Table 2 Comparison <strong>of</strong> survival <strong>of</strong> squamous <strong>cell</strong>/<strong>adenosquamous</strong> <strong>carcinomas</strong> <strong>and</strong> ordinary adeno<strong>carcinomas</strong> <strong>of</strong> the gallbladder<br />

Adenosquamous carcinoma/squamous<br />

<strong>cell</strong> carcinoma median survival (months)<br />

Gallbladder adenocarcinoma<br />

median survival (months)<br />

P-value<br />

All stages 4 12 0.003<br />

(N ¼ 34) (N ¼ 572)<br />

Advanced stages (pT2, pT3, pT4) 4 11.4 0.001<br />

(N ¼ 31) (N ¼ 452)<br />

pT2 stage 14,8 63 0.01<br />

(N ¼ 8) (N ¼ 201)<br />

pT3 stage 21.8 19.3 0.09<br />

(N ¼ 23) (N ¼ 251)<br />

<strong>of</strong> gallbladder adeno<strong>carcinomas</strong> (median ¼ 4 vs 12;<br />

P ¼ 0.003; Figure 12). More importantly, this<br />

adverse prognosis persisted when compared with<br />

stage-matched ‘advanced (pT2, pT3 <strong>and</strong> pT4)’<br />

gallbladder adenocarcinoma cases (n ¼ 452) who<br />

had a median survival <strong>of</strong> 11.4 months (P ¼ 0.01) as<br />

well as with individual stage groups with the<br />

exception <strong>of</strong> T3, which did not reach the same<br />

statistical significance (P ¼ 0.09, Table 2).<br />

The results are summarized in Tables 1 <strong>and</strong> 2.<br />

Discussion<br />

<strong>Squamous</strong> differentiation is rather uncommon in the<br />

gallbladder. In this study <strong>of</strong> 606 invasive <strong>carcinomas</strong>,<br />

which represents the largest cohort to be<br />

analyzed for this purpose to date, squamous differentiation<br />

was detected in 7% <strong>of</strong> the cases. This<br />

figure varied significantly in the literature, ranging<br />

from 1 to 12%, 24–27 presumably mostly due to the<br />

definitional differences. Our study demonstrates<br />

that pure squamous <strong>cell</strong> <strong>carcinomas</strong>, which we<br />

defined as invasive <strong>carcinomas</strong> composed entirely<br />

<strong>of</strong> squamous differentiation, are very uncommon,<br />

constituting only 1% <strong>of</strong> the cases. Rather, squamous<br />

differentiation in the gallbladder is seen mostly<br />

as a secondary component in association with<br />

conventional adeno<strong>carcinomas</strong>. 9,13,14,21,23,25,29,45,46<br />

This focal squamous differentiation can vary in<br />

amount from very minimal, presumably with no (or<br />

negligible) clinical/biological significance, to extensive.<br />

We employed the arbitrary cut<strong>of</strong>f <strong>of</strong> ‘o25%’ to<br />

determine the negligibility <strong>of</strong> this secondary differentiation,<br />

as has been done for the mixed differentiation<br />

<strong>carcinomas</strong> <strong>of</strong> other organs, <strong>and</strong> classified<br />

such cases as adenocarcinoma with focal squamous<br />

change (1% <strong>of</strong> the cases), <strong>and</strong> reserved the diagnosis<br />

<strong>of</strong> <strong>adenosquamous</strong> carcinoma for only those that<br />

have 25–99% <strong>of</strong> the tumor showing squamous<br />

differentiation (4% <strong>of</strong> gallbladder <strong>carcinomas</strong>).<br />

Modern <strong>Pathology</strong> (2011) 24, 1069–1078

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