Lymphatic invasion by tumor cells has been noted infrequently in primary melanomas. Our primary hypotheses were that using immunohistochemical markers of lymphatic vessels and of tumor cells would improve detection of lymphatic invasion and that lymphatic invasion would correlate with regional nodal metastatic disease. This study included 106 patients who were diagnosed between 1972 and 1991 and who had ≥ 10 years of follow up. We performed dual immunohistochemical stains for podoplanin (for lymphatic vessels) and S-100 (for melanoma cells). Lymphatic invasion was identified by light microscopy and confirmed by multispectral imaging analysis. Lymphatic invasion was detected by morphology alone in 5 cases (4.7%) in contrast to immunohistochemical staining augmented by multispectral imaging analysis where 35 cases (33%) were identified (p <0.0001). Lymphatic invasion was significantly associated with time to regional nodal metastatic disease, as well as first metastasis and melanoma-specific death. "Local metastasis", defined by immunohistochemistry-detected lymphatic invasion, satellites or neural invasion, identified 64% of those who had regional nodal metastatic disease within 5 years of diagnosis. Lymphatic invasion is an under-observed phenomenon in primary melanomas that can be better detected by immunohistochemical staining. The presence of lymphatic invasion may be a clinically useful predictor of regionally metastatic disease.

Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas. We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors. Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).

The distinction of ductal adenocarcinoma from chronic pancreatitis remains one of the most difficult challenges in surgical pathology. The glandular units of invasive carcinoma are often well formed with well-polarized cells, appearing deceptively benign. Conversely, the ducts of chronic pancreatitis may be atypical and pseudoinfiltrative as a result of acinar atrophy and fibrosis. We recently noted isolated solitary ductal units (ISDs) in adipose tissue to be a reliable indicator of adenocarcinoma. In this study, the frequency of ISDs was investigated in 105 pancreatic resections with ductal adenocarcinoma and 32 with chronic pancreatitis only. ISD was defined as a solitary gland lying individually in adipose tissue, either directly abutting adipocytes or separated from them by only a thin rim of fibromuscular tissue. ISD was detected in 50/105 (47.6%) of pancreatic resections for ductal adenocarcinoma, but not in any resections with chronic pancreatitis only (specificity 100%; sensitivity 47.6%). Most of the ISDs were very well differentiated and cytologically bland. A small subset of these units represented vascular invasion, in which the carcinoma cells epithelialized the vessel lining, transforming the vessel into a duct-like structure, virtually indistinguishable from normal ducts or PanINs. The vascular nature of these units was verified by Elastic-Van Gieson stain and muscular markers highlighting the elastic lamina and muscular wall, respectively. ISDs were often located in histologic sections taken for the evaluation of the retroperitoneal margin and pancreatic-free surfaces where adipose tissue is more abundant. In conclusion, ISD lying in adipose tissue unaccompanied by other elements, present in 47.6% of pancreatic resections when peripancreatic soft tissues away from the tumor are sampled, is a very specific finding for carcinoma that may be instrumental in the diagnosis and staging of carcinoma as well as margin evaluation.

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