Michael D. Ioffreda

Sterile Inflammation Associated With Transradial Catheterization and Hydrophilic Sheaths

In 1999, we noted the development of inflammation and/or abscesses at the site of radial access in a group of patients. Over a 3‐year period, we noted this inflammation in 33 patients out of 2,038 (1.6%) who had catheterization via the radial approach. The radial abscesses occurred in 30 patients out of 1,063 (2.8%) in whom we could confirm the use of a hydrophilic‐coated sheath, but in no patient for whom we can document that an uncoated sheath was used. No infectious agent could be implicated, and the time course for the development of the abscess, typically 2 to 3 weeks, seemed long for a bacterial infection. Later patients had biopsies, and granulomatous reactions were seen in most. Additionally, a few of the biopsies showed an amorphous extravascular substance consistent with the catheter coating. All patients had good long‐term outcomes. Cathet Cardiovasc Intervent 2003;59:207–213.

Expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during melanoma-induced angiogenesis in vivo.

Recent ultrastructural data indicate that tumor‐induced angiogenesis involves polarized outgrowth of endothelial cells from established vessels into tumor parenchyma and interstitium. Efforts to define the cytoarchitecture of the angiogenic response and to ascertain molecular determinants of polarized endothelial migration have been impeded by lack of sensitive and specific immunologic markers for endothelium and vessel wall components. In this study, we utilized monoclonal antibody to platelet‐endothelial cell adhesion molecule‐1 (PECAM‐1), a cell‐cell adhesion molecule belonging to the immunoglobulin superfamily, to determine extent and patterns of angiogenesis in metastatic melanomas before (N = 7) and after (N = 3) induction of tumor‐infiltrating lymphocyte responses provoked by administration of experimental melanoma vaccine. PECAM‐1 proved to be a more reliable marker for angiogenesis than antibodies to von Willebrand Factor. Although both normal and tumor vessels exhibited prominent staining for PECAM‐1, different patterns of endothelial reactivity were observed. Formation of new vessels was associated with i) PECAM‐1 redistribution from a constitutive circumferential membrane pattern to a pattern restricted to cell‐cell junctions; ii) formation of endothelial cords formed by cell‐cell interactions; and iii) eventual development of open lumens. Vessels within inflamed (vaccine‐treated) and non‐inflamed melanomas did not differ with regard to patterns of PECAM‐1 expression. Forming vessels of inflamed melanomas failed to express the cytokine‐inducible activation marker, E‐selectin. Although normal microvessels and reactive vessels of healing wounds demonstrated prominent staining for α6; laminin receptor, vessels within melanomas showed apparently diminished expression. These data establish PECAM‐1 as a sensitive and specific marker for experimental angiogenesis, and further support the possibility that cell‐cell adhesion mediated by PECAM‐1 may contribute to directed endothelial migration typical of tumor‐induced formation of new vessels.

Multiple familial trichoepitheliomas: a folliculosebaceous-apocrine genodermatosis.

We reviewed the pathologic findings on a family with multiple hereditary trichoepitheliomas. Although the majority of the lesions were trichoepitheliomas, basal cell carcinomas, spiradenomas, and spiradenomas with cylindromatous foci (spiradenocylindroma) were present, representing a spectrum of lesions exhibiting folliculosebaceous (trichoepithelioma, basal cell carcinoma) and apocrine (spiradenoma, spiradenocylindroma) differentiation. Multiple familial trichoepitheliomas may be a syndrome whereby tumors develop from undifferentiated germinative cells of the folliculosebaceous-apocrine unit. Published findings regarding the genetics of this syndrome and solitary trichoepitheliomas are reviewed; although the molecular basis for the tumors has yet to be determined, current data suggest that a tumor suppressor gene may be involved.

Interstitial granulomatous drug reaction to anakinra

Interstitial granulomatous drug reactions are an uncommon entity presenting as asymptomatic, annular, erythematous to violaceous plaques. The incidence of such reactions has been increasing with the use of biologic agents. We report, to the best of our knowledge, the first such reaction to the interleukin (IL)-1 inhibitor anakinra. Our patient presented with pink dermal plaques and nodules in the periaxillary region which resolved with discontinuation of anakinra and recurred upon restarting anakinra. Biopsy revealed a diffuse dermal infiltrate of lymphocytes and histiocytes with interspersed neutrophils and eosinophils. Fragmentation and degeneration of collagen and elastic fibers was also present. Withdrawal of anakinra led to complete resolution of the lesions. Interstitial granulomatous drug reactions are increasing in frequency and we add anakinra to the list of causative agents.

Death receptor apoptosis signaling mediated by FADD in CD30-positive lymphoproliferative disorders involving the skin.

Background:The CD30-positive lymphoproliferative disorders lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and systemic anaplastic large cell lymphoma (S-ALCL) are lesions that overlap clinically, histopathologically, and immunophenotypically. Their biologic behaviors, however, vary considerably. In particular, lesions of LyP regress spontaneously while those of S-ALCL persist and often progress. Apoptosis has been suggested as the mechanism by which the lesions of LyP regress, but the underlying signaling pathways remain unclear. In this study, we used newly developed activation state-specific antibodies to demonstrate apoptosis signaling through the death receptor-mediated pathway regulated by FADD and caspase 3. Methods:Dual immunohistochemistry for CD30 and activated forms of FADD and caspase 3 was performed on cutaneous biopsy specimens from 27 patients with CD30-positive lymphoproliferative disorders involving the skin. The patients included 18 with primary cutaneous CD30-positive LPDs (15 with LyP and 3 with C-ALCL) and 9 with S-ALCL. Results:The proportion of CD30-positive cells expressing activated FADD was significantly different between primary cutaneous CD30-positive lymphoproliferative disorders and S-ALCL (36.4% vs. 14.5%, P = 0.0083). Expression of cleaved caspase 3 was also significantly different between primary cutaneous lesions and S-ALCL (9.2% vs. 1.9%, P = 0.048). Conclusions:Although a larger number of cases should be studied to validate these results, these data provide evidence that differences in signaling through the death-receptor apoptosis pathway mediated by FADD may be responsible for the varying biologic behaviors of CD30-positive lymphoproliferative disorders involving the skin.

Coexistence of Tumid Lupus Erythematosus with Systemic Lupus Erythematosus and Discoid Lupus Erythematosus: A Report of Two Cases of Tumid Lupus

Tumid lupus erythematosus (LE) is a rare variant of chronic cutaneous LE that is characterized clinically by smooth, nonscarring, pink to violaceous papules or plaques without evidence of surface change. Histopathologic features include superficial and deep lymphocytic infiltration in a perivascular and periadnexal distribution, with dermal interstitial mucin deposition and focal or absent dermoepidermal junction involvement. These clinical and histopathologic features can be challenging to differentiate from other cutaneous diseases. This is particularly true because patients with tumid LE usually do not have other manifestations of systemic LE or cutaneous LE. We present 2 cases of tumid LE, one associated with concomitant systemic LE and the other occurring concurrently with discoid LE. Furthermore, we demonstrate the rare occurrence of a patient with tumid LE occurring below the waist at a photo-protected site.

Lymphoepithelioma-like carcinoma of the skin with spindle cell differentiation

Background:  Primary cutaneous LELC is a cutaneous neoplasm with histopathologic features identical to those seen in the undifferentiated subtype of nasopharyngeal carcinoma. It is extremely rare, with only approximately 30 cases reported in the literature.

Cystic basal cell carcinoma or hidrocytoma? The use of an excisional biopsy in a histopathologically challenging case.

Basal cell carcinoma (BCC) has many histologic variants. These variants may show differentiation toward benign and malignant tumors of cutaneous appendages, especially hair follicles. Herein we describe a lesion that was clinically thought to be a BCC, but a superficial biopsy showed histologic features suggestive of an apocrine hidrocystoma. Because of some cytologic atypia, complete excision was recommended. The excision specimen revealed a cystic BCC. The importance of examining the entire neoplasm before reaching a final pathologic diagnosis is emphasized.

A Case of Inflammatory Nonscarring Alopecia Associated With the Tyrosine Kinase Inhibitor Nilotinib

IMPORTANCE Nilotinib, a recently approved multitargeted tyrosine kinase inhibitor targeting the BCR-Abl translocation involved in chronic myelogenous leukemia, reportedly produces alopecia according to the package insert, but clinical and histologic descriptions of the alopecia are lacking. OBSERVATIONS A 33-year-old woman with chronic myelogenous leukemia developed widespread alopecia involving scalp and body hair within weeks after starting nilotinib therapy. Biopsies revealed perifollicular lymphocytic inflammation and evidence of follicular injury but normal hair density, consistent with a nonscarring alopecia. CONCLUSIONS AND RELEVANCE Nilotinib therapy may induce perifollicular inflammation and widespread persistent alopecia. We present the first clinical and histologic description of this potential adverse effect. Further investigation into the underlying mechanism of this adverse effect may produce insights into the hair growth cycle as well as potential therapeutic targets.

Marking of Nail Matrix Biopsies with Ink Aids in Proper Specimen Orientation for More Accurate Histologic Evaluation

Longitudinal melanonychia is a frequently encountered condition in clinical practice and often presents a diagnostic challenge. Despite recent advances in the use of dermoscopy, nail matrix biopsies are still considered the standard for diagnosing pigmented nail lesions. Dermatopathologists are then faced with the daunting task of differentiating the benign from the malignant. Before implementing this technique into our practice, histopathologic sections were often missing epidermis or were tangentially sectioned, making interpretation by the dermatopathologist technically difficult.