Amy Parsons

Transglutaminases: the missing link in nephrogenic systemic fibrosis.

Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), occurs in renal failure patients after gadolinium contrast exposure. The fibrosis of the dermis and subcutaneous septae accompanies fibrosis of other organs, including the heart, liver, lungs, and muscle. The fibrotic skin demonstrates increased dermal collagen, fibroblasts, and mucin. The mechanism by which gadolinium is associated with fibrosis is not known.We tested the hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in the organs, including skin, of renal failure patients exposed to gadolinium contrast.We performed immunohistochemical studies using antibodies to transglutaminase-2, factor XIIIa, transglutaminase isopeptide, and the histiocyte marker CD68 on five archived skin biopsies of NSF. The results indicate that the dermal fibroblasts and histiocytes of NSF express transglutaminase-2, CD68, factor XIIIa, and transglutaminase isopeptide, indicating increased expression and/or activation of transglutaminases in NSF. We recommend further research into the use of transglutaminase inhibitors in the treatment and prevention of NSF.

Retiform hemangioendotheliomas usually do not express D2-40 and VEGFR-3

Retiform hemangioendothelioma (RH) is a rare vascular neoplasm most often occurring in the limbs of middle-aged females. This entity is characterized by infiltrative vascular spaces arranged in a pattern similar to the rete testis. RH differs from angiosarcoma by lacking cytologic atypia and high mitotic rates. This neoplasm frequently recurs but rarely metastasizes. RH tumor cells react with vascular endothelial markers CD31, CD34, and factor VIII-related antigen. A review of the English literature provides only one attempt at staining RH with D2-40, a marker of endothelium of lymphatic vessels, which was negative, and one reported staining of RH with lymphatic endothelial marker VEGFR-3, which was positive. The etiology of RH is unknown. RH has previously been considered closely related to Dabska tumors, which are positive for lymphatic endothelial marker D2-40. We stained 4 RHs with mouse monoclonal antibodies against D2-40 and CD31 and 3 of the 4 RHs with vascular endothelial growth factor receptor 3 (VEGFR-3), to further evaluate whether RH had lymphatic differentiation, in addition to vascular differentiation. Three of the 4 RH biopsies failed to demonstrate D2-40, none expressed VEGFR-3, whereas CD31 was strongly positive, suggesting that RH is a vascular entity which usually does not have lymphatic differentiation, but may rarely express D2-40.

Retrospective Study of Intraepidermal Nerve Fiber Distribution in Biopsies of Patients With Nummular Eczema

Background:Nummular eczema is a chronic inflammatory condition characterized by pruritus and histologically characterized by spongiosis. The etiology is unknown, and the lesions frequently arise spontaneously. Neuropeptides contribute to mediating and maintaining eczematous conditions. Previous research indicates that the number of immunoreactive nerve fibers is increased in pruritic skin lesions. Objective:We sought to determine if the number of immunoreactive nerve fibers is increased in nummular eczema, as in other inflammatory pruritic conditions. Methods:Protein gene product 9.5 (PGP 9.5) was assessed by immunohistochemistry in 22 biopsies of nummular eczema and was compared with immunohistochemical expression of 8 skin biopsies uninvolved by nummular eczema. Results:Nerve fiber distribution using PGP 9.5 stain showed that there was significantly reduced PGP9.5 stain amount in the epidermis of patients with nummular eczema compared with their respective healthy control (P = 0.0054). However, no statistical difference was seen in the papillary dermis. Conclusion:Pruritus of nummular eczema is not associated with an increase of epidermal nerve fiber density and sprouting.

Early histopathologic changes in grover disease.

Background:Grover disease is a clinicopathologic entity characterized by acantholysis. The histologic changes typically occupy circumscribed foci, therefore early stages could go unnoticed and be misdiagnosed. Objective:To report on early histopathologic changes in Grover disease. Material and Methods:We analyzed 22 cases of Grover disease histologically diagnosed at Wake Forest University School of Medicine, NC, between 2000 and 2009. Early changes were defined as elongation of rete ridges and mild focal acantholysis. Results:Six cases (27%) showed elongation of the rete ridges with focal acantholysis. Mild spongiosis was seen in 4 cases. Superficial perivascular inflammatory infiltrate was found in all cases, 5 of which showed eosinophils. Conclusions:These findings may represent a diagnostic clue in cases of early Grover disease, if clinical correlation is made.

A 41-year-old woman with a scaly erythematous plaque admixed with erosions on the groin, back, and legs: challenge. Nutritional deficiency.

A 41-year-old woman with a past medical history of gastric bypass in 2000 with multiple subsequent small bowel obstructions, schizoaffective disorder, multiple personality disorder, and deep venous thrombosis, presented to the Emergency Department with a several day history of poor p.o. intake and failure to thrive. The patient denied nausea, vomiting, diarrhea, and fever. The patient was admitted with a diagnosis of failure to thrive and ileus. On hospital day 12, the patient developed scaly erythematous plaques admixed with erosions on the groin, back, and legs (Figs. 1, 2). A biopsy was performed and sent for routine histologic examination (Figs. 3, 4). What is Your Diagnosis?

Capsular melanocytic nevus: A potential diagnostic pitfall in intraoperative sentinel lymph node evaluation for metastatic melanoma

We report a case of capsular melanocytic nevus morphologically mimicking metastatic melanoma during intraoperative imprint cytology analysis of sentinel lymph nodes for metastatic melanoma. The benign nevus cells stained positively for S-100 protein like melanoma, but were negative for HMB-45, lacked cytologic atypia, and had a distinct intracapsular location, unlike melanoma. These features are useful in distinguishing capsular melanocytic nevi from metastatic melanoma. As a false-positive diagnosis intraoperatively may result in unnecessary lymphadenectomy, pathologists must be aware of capsular melanocytic nevi as potential false-positive interpretation.

Intraoperative imprint cytology for sentinel lymph node evaluation of merkel cell carcinoma: A case report

Merkel cell carcinoma is a rare skin cancer, which is more aggressive and more lethal than melanoma. Merkel cell carcinoma tends to spread to regional lymph nodes and, consequently, lymph node status is the strongest predictor of survival. Of all the staging alternatives, intraoperative sentinel lymph node (SLN) biopsy seems to be the best option by quickly affording clinicians the advantage of averting unnecessary surgery in patients with negative SLNs, while providing the option of continuing on to therapeutic lymph node dissection for patients detected with node-positive disease. For evaluation of SLN biopsies, intraoperative imprint cytology (IIC) demonstrates equivalent sensitivity, specificity, and diagnostic accuracy as frozen sections while offering greater preservation of nuclear and cytoplasmic detail without freezing artifact, retention of all tissue for permanent sections, quicker and less labor intensive preparation, and lower costs. For these reasons, IIC should be the preferred method of examination for SLN biopsies for patients with Merkel cell carcinoma. We report a case of metastatic Merkel cell carcinoma diagnosed by evaluation of SLNs using IIC.