Jeff D. Harvell

Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and molecular pathologic study of 22 cases.

This report describes 22 Spitz nevi that seemed to have been clinically removed but persisted and clinically recurred at the biopsy site. These were evaluated in terms of histopathology, immunohistochemistry, and molecular pathology using comparative genomic hybridization (CGH) and fluorescent in situ hybridization. One of these 22 lesions was originally reported as an atypical melanocytic proliferation with some features of a Spitz nevus and was included in the study set at an early stage but was later recognized as melanoma after metastasis to regional lymph nodes 3 years after the local recurrence. We noted four histopathologic patterns in the recurrent lesions: 1) a predominantly intraepidermal pattern resembling “pseudomelanoma” as seen in recurrent “common” melanocytic nevi, 2) a compound, mostly nested pattern above or within a scar that was nearly identical to the originally biopsied Spitz nevus, 3) a nodular growth pattern that closely simulated invasive melanoma, and 4) a desmoplastic pattern resembling an intradermal desmoplastic Spitz nevus. Although the majority of recurrent lesions exhibited asymmetry and pagetoid spread, the dermal component usually had a low mitotic rate and retained architectural and cytologic maturation, which allowed distinction from invasive melanoma. Except for the metastasizing melanoma, the immunostaining pattern with S-100 and HMB-45 was identical to that previously reported for Spitz nevi. Ki67 revealed a very low proliferation rate in all cases, including the melanoma. CGH performed in 10 cases yielded results consistent with Spitz nevi in eight cases. The remaining two cases showed CGH profiles more typical of melanoma, and one of these was the above-referenced case of melanoma, proven by metastasis. Although ancillary molecular techniques such as CGH are of great help in distinguishing these from melanoma, until such techniques become widely available we advocate complete but conservative excision of any recurrent Spitz nevus.

Percutaneous absorption and inflammation in aged skin: A review

We review experimental studies that address age-related changes in cutaneous barrier function and dermal blood vessel function. These differences have important implications in the understanding of age-related changes in the inflammatory process and topical drug delivery systems.

Spitz's nevi with halo reaction: a histopathologic study of 17 cases

Halo reactions to melanocytic nevi are a well‐recognized phenomenon. In contrast, halo reactions to Spitzs nevi have been reported only infrequently. Halo reactions may cause misdiagnosis of an otherwise benign nevus as melanoma because inflammatory cells sometimes obscure the architectural features of the underlying nevus, and may induce cytologic atypia. For Spitzs nevus where the distinction between malignancy and benignancy is already challenging, halo reactions compound the problem. We describe 17 examples of Spitzs nevus with halo reaction, and compare their immunohistochemical features with those of “ordinary” halo nevi. Only 2 of 17 lesions demonstrated clinically apparent halos. Clinical follow‐up was available for 12 of 17 cases. None of the 12 has persisted at the biopsy site or metastasized after an average 3.6‐year follow‐up period. Junctional, compound, intradermal, and combined types of Spitzs nevi were represented. All were characterized by symmetrical lymphocytic infiltrates which permeated the full thickness of the nevus, including junctional nests. Combined Spitzs nevi constituted more than one‐half of examples in this series (9/17 cases). The combined Spitzs nevus included a combination of Spitzs nevus with either an ordinary (common, banal) nevus or a superficial congenital type nevus. In these combined Spitzs nevi, the lymphocytic response was often directed exclusively to the Spitzs nevic component. Important distinguishing features from malignant melanoma arising in a pre‐existing nevus included symmetry and lateral circumscription of the spitzoid component, no large expansile‐appearing aggregates of melanocytes, a decrease in size of nests with increasing dermal depth, a lack of mitotic figures among melanocytes at the base, and a symmetrical and diffusely permeative lymphocytic response. Although the combined Spitzs nevus with halo reaction sometimes appeared asymmetrical at scanning magnification, each component of the combination was symmetrical, when examined independently. Probably because of reactive atypia, nuclear maturation with progressive descent into the dermis was sometimes absent. There were no obvious differences in immunohistochemical staining patterns among 4 Spitzs nevi with halo reaction, 5 regressing melanomas, and 5 benign halo nevi when stained with antibodies to S100, HMB‐45, OPD4, CDS, TIA‐1, CD1a, CD68, and Ki‐67.

Histogenetic relations between giant cell fibroblastoma and dermatofibrosarcoma protuberans. CD34 staining showing the spectrum and a simulator.

The authors describe three lesions that provide further evidence for a close, possibly histogenetic relation between giant cell fibroblastoma and dermatofibrosarcoma protuberans. The first case involves a dermatofibrosarcoma protuberans that contained a single giant cell fibroblastoma-like focus of multi-nucleate giant cells. A second tumor, a giant cell fibroblastoma, recurred 6 years later as a dermatofibrosarcoma protuberans. In the third lesion, there was a juxtaposition and co-mingling of dermatofibrosarcoma protuberans and giant cell fibroblastoma within the same primary lesion. In all cases, both the giant cell fibroblastoma areas and dermatofibrosarcoma protuberans areas stained positively with CD34. A fourth case, a dermatofibrosarcoma protuberans infiltrated skeletal muscle, creating giant cell fibroblastoma-like giant cell mimics--a result of skeletal muscle degeneration or atrophy with nuclear conglomeration. The latter giant cells failed to express CD34 but did show immunoreactivity with desmin. These findings support the concept that giant cell fibroblastoma and dermatofibrosarcoma protuberans probably represent a histologic spectrum of a single CD34 positive (perhaps, dermal dendrocytic) neoplasm, a conclusion supported by a recently cloned t(7;22) breakpoint demonstrated in both neoplasms.

Contact urticaria and its mechanisms

This paper reviews the syndrome of contact urticaria in terms of current knowledge regarding pathophysiological mechanisms. The three mechanistic categories into which contact urticants are grouped include: (1) immunological contact urticaria, (2) non-immunological contact urticaria and (3) uncertain-mechanism-mediated contact urticaria. Within this schema, the clinical manifestations, diagnosis and therapy of contact urticaria are presented.

Large atypical cells of lymphomatoid papulosis are CD56-negative: a study of 18 cases

Background: Histologically, diffuse dermal infiltrates of large atypical lymphocytes can be seen in lesions as indolent as type C lymphomatoid papulosis (LyP) to ones as aggressive as NK/T‐cell lymphoma. While lesions of lymphomatoid papulosis are definitionally positive for CD30, their ability to express CD56 has not been formally studied. The objective of the current study was to determine whether or not the large atypical cells of LyP express the natural killer cell marker, CD56.

An in Vivo Correlation with Three in Vitro Assays to Assess Skin Irritation Potential

AbstractWe have tested the irritancy of 10 materials of various chemical composition in three in vitro toxicity assays: the Skintex Dermal Assay system (In Vitro International, Irvine, CA, USA), the silicon microphysiometer (Molecular Devices Inc., Menlo Park, CA), and the Living Skin Equivalent (Organogenesis Inc., Cambridge, MA). The purpose was to discover to what degree the in vitro results predict in vivo skin irritation as seen in nine female volunteers over the course of a 5 day cumulative irritancy patch test. Two in vivo assessments of irritancy were made and compared to the in vitro results, a visual scoring system, and a potentially more objective bioengineering assessment: the chromameter. Measures of sensitivity, specificity, positive predictive value, and negative predictive value were used to compare in vitro with in vivo results. Comparison of results using correlation coefficients was avoided since statistically significant rank orders could not be demonstrated for either in vitro or in v...

In Vitro Skin Irritation Assays: Relevance to Human Skin

The events occurring in primary skin irritation in vivo represent a complex series of chemical and physiological changes. Animals have been used to assess dermal irritation by observation of visible changes ranging from erythema and edema to corrosion and ulceration in the in vivo Draize rabbit skin test accepted by many regulatory agencies [Draize et al., 1944]. These responses, easily observed, are produced by diverse mechanisms.

Comparison of in vitro and human in vivo dermal irritancy data for four primary irritants.

The value of the Skintex dermal assay system as a means of predicting the irritancy of four primary irritants at various concentrations was investigated. The four compounds tested were: benzalkonium chloride at 0.1%, 0.5%, 1.0% and 2.0%; hydrochloric acid at 2.0%, 5.0%, 10% and 20%; phenol at 3.0%, 7.5%, 10%, 12%, 15% and 20%; trichloracetic acid at 7.5%, 10%, 20% and 30%. The results from the in vitro system were compared with published human in vivo data, which was obtained using 100 volunteers, and which graded the irritant reactions using a visual scale. A 2 x 2 contingency table was constructed and the following parameters of the assay were determined: sensitivity, 82%; specificity, 71%; and positive predictive value, 82%. The in vivo dose-response curves for each of the four substances were compared with the in vitro dose-response curves, and correlation coefficients were calculated. The in vitro dose-response curves for benzalkonium chloride (r(2) = 0.987) and phenol (r(2) = 0.994) were strikingly similar to those generated in vivo, possibly indicating that the mechanisms of action in vivo and in vitro are similar for these two compounds. These studies should be extended to a broader variety of chemicals before unknowns can be characterized with a reasonable degree of certainty using this in vitro method.