CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
An interobserver study of reproducibility in subtyping pulmonary adenocarcinomas
Histological subtyping of pulmonary adenocarcinoma has been updated based on predominant pattern, but data on reproducibility are required for validation. The authors conducted a two-part study in which they assessed reproducibility in subtyping adenocarcinomas and then assessed further the distinction between invasive and non-invasive (wholly lepidic) patterns of adenocarcinoma among an international group of pulmonary pathologists. Two ring studies were performed using a microphotographic image-based method, evaluating selected images of lung adenocarcinoma histologic patterns. In the first study, 26 pathologists reviewed representative images of typical and “difficult” histologic patterns. A total number of scores for the typical patterns combined (n=94) and the difficult cases (n=21) were 2,444 and 546, respectively. The mean kappa score (± standard deviation) for the five typical patterns combined and for difficult cases were 0.77±0.07 and 0.38±0.14, respectively. Although 70 percent of the observers identified 12 percent to 65 percent of typical images as single pattern, highest for solid and least for micropapillary, the predominant pattern was recognized in 92 percent to 100 percent of the images, except for micropapillary pattern (62 percent). For the second study on invasion, which was identified as a key problem area from the first study, 28 pathologists submitted and reviewed 64 images representing typical and difficult examples. The kappa score for typical and difficult cases was 0.55±0.06 and 0.08±0.02, respectively, with consistent subdivision by the same pathologists into invasive and non-invasive categories due to differing interpretations of terminology defining invasion. In pulmonary adenocarcinomas with classic morphology, which comprise the majority of cases, there is good reproducibility in identifying a predominant pattern and fair reproducibility in distinguishing invasive from in situ (wholly lepidic) patterns. However, more precise definitions and better education relative to interpreting existing terminology are required to improve recognition of purely in situ disease, an area of increasing importance.
Thunnissen E, Beasley MB, Borczuk AC, et al. Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study. Mod Pathol. 2012;25(12):1574–1583.
Correspondence: Dr. E. Thunnissen at e.thunnissen@vumc.nl
Value of PAX8, PAX2, claudin-4, and h-caldesmon in identifying peritoneal epithelioid mesotheliomas
Distinguishing between peritoneal epithelioid mesotheliomas and papillary serous carcinomas involving the peritoneum can be difficult using routine histological preparations, but this differential diagnosis can be facilitated using immunohistochemistry. Recent investigations have indicated that the immunohistochemical markers PAX8, PAX2, claudin-4, and h-caldesmon can help distinguish between these two malignancies. However, much of the published information about the value of these markers is insufficient or contradictory. The authors conducted a study to resolve some of the controversies and to determine the practical value of these markers for assisting in the differential diagnosis of peritoneal mesotheliomas and serous carcinomas. They investigated 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas (15 primary and 30 metastatic to the peritoneum). PAX8 and PAX2 nuclear positivity was demonstrated in 42 (93 percent) and 25 (56 percent) of the serous carcinomas, respectively, whereas none of the mesotheliomas expressed either marker. Forty-four (98 percent) of the serous carcinomas exhibited claudin-4 reactivity along the cell membrane, whereas none of the mesotheliomas were positive for this marker. All of the serous carcinomas and mesotheliomas were negative for h-caldesmon. The authors concluded that PAX8 and claudin-4 have a higher sensitivity and specificity for helping discriminate between peritoneal epithelioid mesotheliomas and serous carcinomas when compared with all other positive carcinoma markers that are recommended for inclusion in the immunohistochemical panels used in this differential diagnosis. Even though it is highly specific, PAX2 has low sensitivity, so it is of little practical value in diagnosing peritoneal epithelioid mesotheliomas. H-caldes-mon is not useful.
Ordóñez NG. Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas. Mod Pathol. 2013;26:553–562.
Correspondence: Dr. N. G. Ordóñez at nordonez@mdanderson.org
Clinicopathologic study of cutaneous digital papillary adenocarcinoma
Aggressive digital papillary adenocarcinoma is a rare tumor predominantly involving the distal end of digits. The authors examined 31 cases of this distinctive tumor for clinicopathologic, immunohistochemical, and followup data when available. Males who were a mean age of 43 years (range, 14 to 67 years) were predominantly affected (n=29). Three lesions were reported in patients younger than 20 years old. All cases involved a finger (n=26) or a toe (n=5), with most involving the distal portion of the digit (n=29). Two lesions involved the base of the digit, or web space. Histopathologically, all tumors involved the dermis, with subcutaneous extension in 14 cases. The lesions demonstrated a multinodular solid or cystic pattern, or both, with focally infiltrative architecture in 21 cases. Papillary projections were prominent (n=10), focal (n=15), or not identified (n=6). Within the solid component, tubular structures were present, at least focally, in all cases. Cytologic atypia ranged from mild (n=8) to moderate (n=20) but was focally severe in three cases. Mitotic count ranged from less than one to 18 per millimeter. Focal necrosis was seen in six cases. Immunohistochemically stained sections were available for review in eight cases. Tumor cells were diffusely positive for MNF116 (three of three). Carcinoembryonic antigen and epithelial membrane antigen highlighted the luminal border of tubules (eight of eight). Smooth muscle actin (five of six) and calponin (six of six) highlighted a myoepithelial layer around tubular/glandular structures, as did p63 (two of two) and podoplanin (five of five). Followup after excision or amputation (n=23; range, two months to 21 years) revealed local recurrence (n=5) and metastatic disease (n=6; lymph node in one, lungs in four, and both lymph node and lung in one). Metastases were noted at presentation in two cases (lymph node in one and lung in one), but presented as late as 14 and 20 years in lymph node and lung, respectively. Only one patient died of metastatic disease six years after initial diagnosis, after multiple recurrences and lung metastases. Three patients were alive with progressive disease up to 24 months after developing lung metastases. Histopathologic features did not predict outcome. The presence of tumor-associated myoepithelial cells histologically and immunohistochemically was not synonymous with benign-ity. Wide excision and partial digit amputation significantly reduced recurrence and metastatic rates. The authors concluded that a delayed occurrence of metastases and a protracted course despite metastatic disease necessitates long-term followup. And because the name implies a malignant neoplasm, the rubric “aggressive” is unnecessary.
Suchak R, Wang WL, Prieto VG, et al. Cutaneous digital papillary adenocarcinomas: a clinicopathologic study of 31 cases of a rare neoplasm with new observations. Am J Surg Pathol. 2012;36(12):1883–1891.
Correspondence information not provided.