Anneli R. Bowen

Proliferation, Apoptosis, and Survivin Expression in Keratinocytic Neoplasms and Hyperplasias

The dysregulation of apoptosis occurs in many cutaneous disease states. Several apoptosis inhibitors have been shown elevated in neoplasms and in some inflammatory conditions, but their relation to proliferative and apoptotic states has not been defined. We examined the expression of the apoptosis inhibitor survivin in a panel of keratinocytic neoplasms and hyperproliferative skin lesions using both immunohistochemistry and a newly developed in situ hybridization technique. Proliferation and apoptotic indices were also assessed by immunohistochemical staining for proliferating cell nuclear antigen and TUNEL, respectively. We found the highest rate of proliferation in verrucae and psoriasis followed by actinic keratosis, squamous and basal cell carcinoma, lichen simplex chronicus, and seborrheic keratosis; all were significantly (P < 0.05) higher than normal skin. Apoptotic rate was increased in squamous (P = 0.05) and basal cell carcinoma (P = 0.03), but not significantly different from normal skin in the other lesions tested. Survivin expression was seen in most neoplasms and hyperproliferative lesions, but not normal skin. Survivin expression was often restricted to the upper third of the epidermis in psoriasis and lichen simplex chronicus, whereas all the other lesions stained diffusely. Survivin expression appears to be a consistent feature of keratinocytic neoplasms and hyperproliferative lesions and may contribute to the formation of epidermal hyperplasia seen in all of these disease states.

Fibroepithelioma of pinkus is a fenestrated trichoblastoma

Pinkus described “pre-malignant fibroepithelioma” as a proliferation that gave rise to many tiny basal cell carcinomas within each lesion. Later authors have generally considered it to be an unusual variant of basal cell carcinoma (BCC). The delineation of trichoblastoma as the general term for the benign counterpart of BCC raises the possibility that the fibroepithelioma of Pinkus (FEP) would be better classified under that rubric. To address this subject, we examined the records of 114 patients with FEP for body site, age and sex distribution, and sections from 75 lesions. All FEP examined show a blunt interface with the underlying dermis (where one could be seen), differentiation toward follicular bulbs and papillae, and large areas of cellular stroma. FEP has a slight female preponderance in contrast to BCC, which is more common in males. Unlike the common types of BCC, FEP has an overwhelming predilection for the trunk and extremities, and only 5% of tumors are set in a dermis with significant amounts of solar elastosis. Next, FEP, BCC, and FEP with BCC-like areas were stained with MIB-1 (to assess proliferation), p53 (an oncogene product), and CK20 (a Merkel cell marker) antisera. FEP shows a low level of staining for p53 and MIB-1, in contrast to conventional BCCs that over-express these markers. FEP also shows retention of Merkel cells, a characteristic of benign neoplasms with follicular germinative differentiation but not in general of BCC. The BCC-like areas in some FEP tumors reflect these staining tendencies with less striking differences. Given the contrast between FEP and BCC with respect to site of occurrence, relationship to sun damage, histopathologic features, and immunohistochemical studies, it appears that FEP more closely resembles trichoblastoma than BCC.

The role of vulvar skin biopsy in the evaluation of chronic vulvar pain

Sixty-one percent of refractory vulvodynia patients evaluated in a tertiary care vulvovaginal clinic had clinically relevant dermatoses based on dermatopathologist-analyzed vulvar biopsy including: lichen sclerosus, allergic/irritant dermatitis, lichen planus, and other inflammatory or neoplastic dermatoses. Given the frequency of dermatologic disease, vulvar biopsy and analysis by a dermatopathologist are recommended in patients with vulvodynia.

Proliferation, apoptosis, and survivin expression in a spectrum of melanocytic nevi

Background:  Apoptosis is important for maintenance of tissue homeostasis and often dysregulated in cutaneous neoplasms. The apoptosis inhibitor survivin is expressed in melanoma and non‐melanoma skin cancers and benign keratinocytic lesions. Its expression has not been studied in melanocytic nevi.

Seborrheic keratoses: A study comparing the standard cryosurgery with topical calcipotriene, topical tazarotene, and topical imiquimod

Background  Patients with seborrheic keratoses frequently desire an effective topical therapy for seborrheic keratoses.

Immunohistochemical staining with Melan-A of uninvolved sun-damaged skin shows features characteristic of lentigo maligna.

BACKGROUND The greater density and unusual patterning of melanocytes in chronically sun‐exposed skin complicates interpretation of intraoperative Melan‐A immunohistochemical stained margins during margin‐controlled surgery for lentigo maligna (LM) and lentigo maligna melanoma (LMM). OBJECTIVE To identify the immunohistochemical similarities and differences in melanocyte distribution between LM and LMM and chronically sun‐exposed skin. METHODS Retrospective review of Melan‐A‐stained original biopsy specimens of LM and LMM and uninvolved sun‐damaged skin (negative controls), from 70 LM and LMM cases from the University of Utah in 2008. RESULTS Histologic features commonly associated with LM were common in negative controls from chronically sun‐exposed skin. Melanocyte confluence (27/70, 39%), stacking (34/70, 49%), theque formation (9/70, 13%), adnexal extension (59/68, 87%), and suprabasilar scatter (23/70, 33%) were observed in the negative controls from sun‐damaged skin. Such features were present nearly uniformly in the LM and LMM specimens. Epidermal melanocyte density in LM and LMM differed significantly from that in negative controls (82.7 ± 29.3 and 25.6 ± 9.3 per × 400 field, respectively; p<.001). CONCLUSION Epidermal melanocytic features often ascribed to LM, such as melanocyte confluence, stacking, theque formation, adnexal extension, and suprabasilar scatter, are frequently observed in chronically sun‐exposed Caucasian skin and may lead to overestimation of surgical margins. The authors have indicated no significant interest with commercial supporters.

Pseudoxanthoma elasticum-like fibers in the inflamed skin of patients without pseudoxanthoma elasticum.

Background:  Pseudoxanthoma elasticum (PXE) is an inherited disorder leading to characteristic calcified elastic fibers in skin, eyes and vasculature. PXE‐like fibers have not been described in inflammatory skin disease in the absence of other signs of PXE.

Use of proliferation rate, p53 staining and perforating elastic fibers in distinguishing keratoacanthoma from hypertrophic lichen planus: a pilot study

Background: Distinguishing keratoacanthoma (KA) and hypertrophic lichen planus (LP) histopathologically can be difficult, and the challenge is compounded by the tendency of KA to arise in association with hypertrophic LP.

Merkel Cell Carcinoma: Current Issues Regarding Diagnosis, Management, and Emerging Treatment Strategies.

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous tumor with a predilection for the head and neck of elderly Caucasian patients. Although much less common than melanoma, MCC has higher rates of sentinel lymph node involvement, local and regional recurrences, and mortality. The majority of MCC cases have been linked to the relatively newly discovered Merkel cell polyomavirus, which is a ubiquitous constituent of the skin flora. Recent discoveries regarding viral integration and carcinogenesis and the immunologic features of MCC have expanded the understanding of MCC. These discoveries have led to the development and application of emerging therapies such as somatostatin analogs, immune checkpoint inhibition, adoptive cell therapy, and other exciting possibilities for targeted therapy.

Polarizable elements in scabies infestation: a clue to diagnosis

The diagnosis of scabies infestation is straightforward in cases where mite parts are largely visible; however, mites are often not captured in a specimens planes of section. Polariscopic examination is a fast and simple adjunctive diagnostic tool to light microscopy. We describe the unique polariscopic findings in scabies infestation. Two cases of crusted scabies and eight cases of typical scabies were subjected to polariscopic examination. Diagnostic mite parts were visualized in at least one section in all cases. Attached and detached spines as well as scybala (fecal material) are polarizable. Specifically, spines show a polarizable outer sheath with dark central core while scybala show peripherally concentrated, stippled birefringence. Similar stippled birefringence is visible within the gut of some mites whereas significant birefringence is not appreciated in other mite parts. These results suggest that polariscopic examination is a helpful clue in the diagnosis of scabies infestation, especially in cases where the body of the mite is not visualized.