Pediatric hematidrosis - A case report and review of the literature and pathogenesis.

Hematidrosis is a disorder in which blood-tinged fluid exudes from uninjured skin or mucosa. It is often classified as an eccrine sweat disorder, though the precise mechanism-including involvement of sweat glands-has yet to be proven. In contemporary case reports, hematidrosis appears most frequently in the pediatric population, with 83% of cases in the literature since 2008 occurring in individuals 18 years old or younger. We present here a case of a 10-year-old girl with hematidrosis followed by a review of the literature, with an emphasis on the features of this condition in the pediatric population.

Lymphoid aggregates in desmoplastic melanoma have features of tertiary lymphoid structures.

Desmoplastic melanomas (DM) have unique and challenging clinical presentations and histomorphology. A characteristic feature is the presence of scattered lymphoid aggregates. However, the nature of these aggregates is not defined. We hypothesized that they may be tertiary lymphoid structures (TLS), and may be associated with programmed death ligand 1 (PD-L1) expression. We searched our tissue database for 'pure' DMs and for scars as control tissues, collected clinical information, and reviewed H&E histology. We performed multispectral imaging after staining for CD8, CD20, PNAd, FoxP3, CD83, and Ki67, and assessed PD-L1 expression by immunohistochemistry. Pure DM samples were evaluable in 11 patients. All had desmoplastic stroma and lymphoid aggregates on H&E. The lymphoid aggregates of eight of the 11 (72%) DM samples and only three of the 11 scars contained features of TLS, defined as distinct clusters of B cells and CD8 T cells, CD83 dendritic cells in T-cell zones, and PNAd vasculature resembling high endothelial venules. PD-L1 was expressed by at least 1% of melanoma cells in six and by at least 5% of immune cells in 10 of the 11 DM samples. We found that most lymphoid aggregates in DM are organized, classical TLS. PD-L1 expression was detected in most cases and was highest in two cases of DM with TLS. However, low PD-L1 expression in some cases suggests that some DM cells may be unresponsive to interferon-γ. TLS support antigen presentation and T-cell responses in chronic inflammation and cancer. Their presence in DM likely reflects an adaptive immune response, which may be enhanced with immune therapies.

Perivascular Adipose Tissue Harbors Atheroprotective IgM-Producing B Cells.

Adipose tissue surrounding major arteries (Perivascular adipose tissue or PVAT) has long been thought to exist to provide vessel support and insulation. Emerging evidence suggests that PVAT regulates artery physiology and pathology, such as, promoting atherosclerosis development through local production of inflammatory cytokines. Yet the immune subtypes in PVAT that regulate inflammation are poorly characterized. B cells have emerged as important immune cells in the regulation of visceral adipose tissue inflammation and atherosclerosis. B cell-mediated effects on atherosclerosis are subset-dependent with B-1 cells attenuating and B-2 cells aggravating atherosclerosis. While mechanisms whereby B-2 cells aggravate atherosclerosis are less clear, production of immunoglobulin type M (IgM) antibodies is thought to be a major mechanism whereby B-1 cells limit atherosclerosis development. B-1 cell-derived IgM to oxidation specific epitopes (OSE) on low density lipoproteins (LDL) blocks oxidized LDL-induced inflammatory cytokine production and foam cell formation. However, whether PVAT contains B-1 cells and whether atheroprotective IgM is produced in PVAT is unknown. Results of the present study provide clear evidence that the majority of B cells in and around the aorta are derived from PVAT. Interestingly, a large proportion of these B cells belong to the B-1 subset with the B-1/B-2 ratio being 10-fold higher in PVAT relative to spleen and bone marrow. Moreover, PVAT contains significantly greater numbers of IgM secreting cells than the aorta. ApoE-/- mice with B cell-specific knockout of the gene encoding the helix-loop-helix factor Id3, known to have attenuated diet-induced atherosclerosis, have increased numbers of B-1b cells and increased IgM secreting cells in PVAT relative to littermate controls. Immunostaining of PVAT on human coronary arteries identified fat associated lymphoid clusters (FALCs) harboring high numbers of B cells, and flow cytometry demonstrated the presence of T cells and B cells including B-1 cells. Taken together, these results provide evidence that murine and human PVAT harbor B-1 cells and suggest that local IgM production may serve to provide atheroprotection.

Histopathologic review of negative sentinel lymph node biopsies in thin melanomas: an argument for the routine use of immunohistochemistry.

Sentinel lymph node biopsy (SLNB) is performed for some thin melanomas in the presence of concerning histopathological features. There are no defined standards for how sentinel nodes should be processed to detect microscopic metastases. We compared our method of serially sectioning nodes at 2-3 mm intervals and performing one hematoxylin and eosin (H&E) slide versus multiple H&E levels and utilizing immunohistochemistry (IHC). This was a retrospective review of a prospectively collected database identified patients with thin melanomas treated with wide local excision and SLNB between 1995 and 2010. Two patients had positive nodes. Out of 95 patients with negative SLNBs, 48 (49 nodes) patients were evaluable. Additional sections of each SLNB tissue block were stained with H&E (×2), Melan-A (×2) and HMB45 (×2), and reviewed by two pathologists. Additional histopathological sections showed that 1/49 (2.0%) nodes originally called negative had evidence of metastasis, which was evident both on additional H&E levels and by IHC; 3/49 (6.1%) nodes had benign nodal rests. All other nodes (45/49, 91.8%) were negative by H&E and IHC for metastatic disease. This study supports previous work suggesting the value of IHC in detecting micrometastases in melanoma sentinel nodes. Especially for thin melanomas where metastases are uncommon, but where detection of the metastasis upstages considerably from stage IA to IIIA, evaluation of nodes may be enhanced by combining breadloafing at 2-3 mm intervals with multiple H&E sections and IHC analysis.