Histologic features and cytologic techniques that aid pathologic stage assessment of colonic adenocarcinoma.

Cancer involvement of the colonic serosa is designated pT4a by the American Joint Committee on Cancer Staging Manual, 7th edition. The manual defines criteria for pT4a as either tumor penetration of the serosa or comingling of cancer cells and mesothelial cells in histologic sections. Unfortunately, the pT4a grouping is inconsistently applied, because these guidelines are overly limited: fibroinflammatory changes near the serosa may be associated with peritoneal metastases even in the absence of overt peritoneal penetration. Thus, reliable ancillary techniques for detecting serosal penetration by the tumor and accurate criteria for stage assessment are needed. We evaluated the utility of cytologic preparations in determining tumor stage by comparing results of serosal scrape cytology with histologic stage assessment of 120 colon cancer resection specimens. We correlated our findings with the presence and type of inflammatory changes near the serosa to determine which, if any, are reliable indicators of peritoneal penetration. Cytologic smears from all pT1 and pT2 tumors were negative for carcinoma. However, 13 (19%) pT3 tumors showed cancer in cytologic smears, all of which were deeply invasive. In fact, 46% of pT3 cancers present ≤1 mm from a serosal tissue reaction were associated with cancer in cytologic preparations from the serosa, which was comparable to pT4a tumors (55%). We conclude that cytologic smears improve detection of peritoneal penetration among pT3 tumors compared with histology alone. Tumors close (≤1 mm) to a fibroinflammatory tissue reaction on the serosa are likely associated with peritoneal involvement by cancer. Peritumoral abscesses that communicate with the serosa and hemorrhage or fibrin on the serosa also predict cancer involvement of the peritoneum. The presence of these findings among deeply invasive cancers should prompt their classification as pT4a lesions.

ALK+ large B-cell lymphoma: a rare variant of aggressive large B-cell lymphoma mimicking carcinoma on cytology specimens.

Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK+ LBCL) was recognized as a distinct entity by the 2008 WHO classification of lymphomas. Histologically, the tumor cells exhibit either plasmablastic or immunoblastic morphology, with characteristic granular staining for ALK. The purpose of this study is to evaluate the cytologic findings of ALK+ LBCL. The cytologic material obtained by needle biopsy from three cases of ALK+ LBCL was evaluated. All lesions were nodal and the cytologic material analyzed included air-dried and alcohol-fixed slides stained with modified Giemsa and/or HE stains. The following morphologic criteria were assessed: cellularity, cluster characteristics, cell size, cytoplasmic and nuclear characteristics, and background composition. The cytology specimens obtained from the needle biopsies were moderately to highly cellular and composed of a population of large cells with immunoblastic or plasmablastic morphology. Single cells were present in all three cases, but two cases also showed the presence of clusters with acinar and papillary architecture. Multinucleation was noted in all three cases. Amorphous metachromatic background material was noted focally in the modified Giemsa stained slides in all three cases. Immunostains performed on cytology specimens showed cytoplasmic immunoreactivity for ALK, with characteristic granular features. ALK+ LBCL is a rare recently recognized type of lymphoma with unique morphologic and immunophenotypic findings that can mimic epithelial tumors. Recognition of this potential diagnostic pitfall is critical to prevent unnecessary additional work-up and mistreatment.

Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing.

INTRODUCTION: The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR and KRAS molecular testing. The aim of this study was to comprehensively review the performance of cytologic specimens for the above two goals in a high-volume clinical practice. METHODS: Subtyping of primary lung carcinomas by preoperative cytology was correlated with subsequent resection diagnoses during a 1-year period (n = 192). The contribution of various clinicopathologic parameters to subtyping accuracy and utilization of immunohistochemistry (IHC) for NSCLC subtyping were analyzed. In addition, the performance of cytologic specimens submitted for EGFR/KRAS molecular testing during a 1-year period (n = 128) was reviewed. RESULTS: Of the 192 preoperative cytology diagnoses, tumor subtype was definitive versus favored versus unclassified in 169 (88%) versus 15 (8%) versus 8 (4%) cases, respectively. Overall accuracy of cytologic tumor subtyping (concordance with histology) was 93% and accuracy of definitive diagnoses 96%. For a group of patients with ADC and SqCC (n = 165), the rate of unclassified cytologic diagnoses was 3% and overall accuracy 96%. IHC was used for subtyping of 9% of those cases, yielding 100% accuracy. The strongest predictors of difficulty in subtyping of ADC and SqCC were poor differentiation (p = 0.0004), low specimen cellularity (p = 0.019), and squamous histology (p = 0.003). Of 128 cytologic specimens submitted for molecular testing, 126 (98%) were suitable for analysis, revealing EGFR and KRAS mutations in 31 (25%) and 25 (20%) cases, respectively. CONCLUSIONS: Cytologic subtyping of NSCLC is feasible and accurate, particularly when morphologic assessment is combined with IHC. Furthermore, routine cytologic specimens can be successfully used for EGFR/KRAS mutation analysis. Our data strongly support the suitability of cytologic specimens for the new therapeutic paradigms in NSCLC.

Secretory carcinoma in the axilla: probable origin from axillary skin appendage glands in a young girl.

Invasive carcinoma in the axilla may arise from skin appendage glands or ectopic breast tissue or it may be a metastasis. Carcinomas of the skin adnexal glands and breast can be difficult to distinguish from each other as they often display the same patterns of growth. Tubular, cribriform, papillary, apocrine, mucinous, and adenoid cystic are histologic types of carcinoma seen in the breast and skin appendage glands. To our knowledge, secretory carcinoma, the most common form of mammary carcinoma in children, has not yet been described as a morphologic pattern of skin adnexal carcinoma, although we cannot exclude the possibility that such a case was reported with a different diagnosis. We report a case of a young girl with secretory carcinoma that seems to have arisen from skin appendage glands in the skin of the axilla in the absence of demonstrable ectopic breast tissue.

The "Rosen Triad": tubular carcinoma, lobular carcinoma in situ, and columnar cell lesions.

The histologic triad of tubular carcinoma (TC), columnar cell lesion (CCL), and lobular carcinoma in situ (LCIS) has been recognized, but has not yet been fully characterized. The "Rosen Triad"-named in tribute to its first categorical description by the eponymous pathologist-is a morphologic observation that may have important clinical and pathologic implications. To study these implications, the literature on the topic was reviewed. Our own institution's experience with this triad was also reviewed via a study of clinicopathologic material from all TCs diagnosed at excision during a 5-year period (2001 to 2006). The diagnosis of TC was confirmed in 86 of our cases, and relevant patient data were analyzed. TC was associated with some degree of CCL in all (100%, 86/86) cases and with LCIS in 53% (46/86) of cases. Although cases of TC that were associated with LCIS (vs. those not associated with LCIS) seemed to be slightly more likely to have multifocal TC, have another synchronous higher-grade invasive carcinoma and show nodal positivity, these differences were not found to be statistically significant (P<0.05). All 3 lesions (TC, CCL, and LCIS), whenever tested, were estrogen receptor positive, progesterone receptor-positive, and Her-2/neu negative. On the basis of our review of the literature and our own experience, until such time as the biologic explanation and clinical implication of this triad is further elucidated, we recommend that pathologists be aware of this triad and should proactively seek the other 2 lesions if any one of these elements of this triad is identified in any diagnostic breast tissue.