Polyclonal Napsin A Expression: A Potential Diagnostic Pitfall in Distinguishing Primary From Metastatic Mucinous Tumors in the Lung

Abstract

Context.-Napsin A is a useful marker for distinguishing primary from metastatic lung tumors. Mucinous lung tumors may be difficult to distinguish from metastatic mucinous tumors.Objectives.-To evaluate napsin A expression in lung and extrapulmonary mucinous tumors on both histology and cytology specimens and to determine napsin A's utility in differentiating primary from metastatic mucinous tumors.Design.-Napsin A immunohistochemistry was performed using a rabbit polyclonal antibody on formalinfixed, paraffin-embedded surgical and fine-needle aspiration biopsy-derived, paraffin-embedded cell block specimens. Positive expression was defined as coarse, granular, cytoplasmic staining in 10% or more of tumor cells.Results.-Sixteen of 32 mucinous lung tumors (50%) and 16 of 33 extrapulmonary mucinous tumors (48%), including 15 of 18 of gastrointestinal origin (83%), expressed napsin A. Positivity was concordant between surgical and cell block specimens in 5 of 9 cases (56%). In 3 of 4 discordant cases, napsin A expression was detected on the surgical specimen but not the cell block. The cell block material in these cases was paucicellular.Conclusions.-Napsin A shows decreased sensitivity and specificity for mucinous lung tumors and is unlikely to be reliable as a sole immunohistochemical marker of lung origin for such tumors (52% specificity in this study). The high frequency of napsin A expression in gastrointestinal mucinous tumors makes it particularly unreliable in distinguishing metastatic gastrointestinal from primary lung mucinous tumors. However, napsin A expression analysis may facilitate distinguishing mucinous tumors of pulmonary from those of nongastrointestinal origin. Interpretation of napsin A staining may be problematic in mucinous tumor specimens of low cellularity such as cell blocks.

Nonspecific Reactivity of Polyclonal Napsin A Antibody in Mucinous Adenocarcinomas of Various Sites: A Word of Caution

“…In our laboratory, we noticed a particularly extensive, puzzling reactivity with p-Napsin A in mucinous adenocarcinomas of various sites, regardless of the site of origin. Such reactivity of p-Napsin A was also recently noted by Heymann et al, 5 but without confirmation of whether those tumors were negative for m-Napsin A. To address this issue we compared staining of p-Napsin A (Ventana/Cell Marque, Tucson, Arizona) and mNapsin A (clone IP64, Leica Biosystems/Novocastra, Buffalo Grove, Illinois) in whole-tissue sections from resected mucinous adenocarcinomas of lung (n ¼ 8) and extrapulmonary sites (n ¼ 13), including appendiceal, ovarian, colorectal, and pancreatic.…”

“…It is possible that this high degree of nonspecific reactivity may be related to particular staining conditions in our laboratory, because in the two prior publications nonspecific reactivity of p-Napsin A in mucinous carcinomas was significant but not universal. 2,5 Of note, p-Napsin A staining was not entirely indiscriminate in our laboratory, because p-Napsin A did not label a large series of unrelated tumors, including squamous cell carcinomas, small cell carcinomas, and carcinoid tumors. 6 The reason for the affinity of p-Napsin A for mucinous neoplasms is not clear.…”

Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer

“…157 Interestingly, other studies using a polyclonal antibody reported napsin A expression in none of 49 nonpulmonary mucinous adenocarcinomas 155,156 ; thus, the low specificity reported in the former study may be attributed to its particular IHC platform. 157,164 Further, nonspecific labeling with polyclonal napsin A in mucinous adenocarcinomas appears to have peculiar supranuclear localization, as opposed to the pan-cytoplasmic granular staining present with monoclonal napsin A, possibly owing to cross-reaction with panmucin antigen by the polyclonal antibody (see Fig. 14).…”

Rapidly progressing lepidic pulmonary metastases from a treated poorly differentiated hepatocellular carcinoma demonstrating new pathologic features of cholangiocarcinoma: A potential diagnostic pitfall that may mimic pneumonia

“…In our patient, antibiotic treatment failure, the presence of atypical cells, and nonresolving consolidation raised concern for an unusual pattern of metastatic disease and a primary pulmonary adenocarcinoma. Studies have described high positive predictive values in diagnosing primary pulmonary adenocarcinoma with individual positivity of either TTF-1 (72%) or napsin A (83%) and higher specificity when positivity was demonstrated with both markers [26] , [27] , [28] . Our patient was negative for TTF-1 and napsin A, making primary pulmonary adenocarcinoma very unlikely.…”