Faculty Bibliography

Multiple cutaneous and uterine leiomyoma (MCL), or Reed syndrome is an uncommon condition that includes cutaneous piloleiomyomas and internal neoplasms of the uterus and kidney. Clinical findings include clusters of variably-painful, skin-colored-to-red-brown papules. Genetic testing shows germline mutations in the gene encoding fumarate hydratase. We describe a patient with MCL who presented with subtle cutaneous findings. We believe it is important that dermatologists consider a diagnosis of MCL when presented with patients with small painful dermal papules.

BACKGROUND:Acute skin erythematous lesions that follow allogeneic hematopoietic stem cell transplantation (HSCT) and are histologically diagnosed as graft-versus-host disease (GVHD) are often associated with reactivation of latent herpes simplex virus (HSV). OBJECTIVE:To further examine the relationship between reactivated HSV and GVHD development. METHODS:We present 3 patients with acute skin GVHD after allogeneic HSCT who were studied prospectively for expression of the HSV antigen Pol, which is involved in HSV-associated erythema multiforme. RESULTS:Pol was expressed in the GVHD lesions but not the pre-HSCT normal skin or peripheral blood mononuclear cells. Lesion severity correlated with the Pol levels but not the histopathologically defined GVHD grade. Lesion development was accompanied by increased numbers of Pol+ circulating/skin-infiltrating CD34+ stem cells and CD1a+ and other dermal dendritic cells. CONCLUSIONS:Subclinical HSV infection of circulating CD34+ cells can contribute to some post-HSCT skin lesions histologically diagnosed as GVHD, with potential preventive and therapeutic implications.

BACKGROUND:Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). MATERIALS AND METHODS/METHODS:Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). RESULTS:Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p < 0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = -0.06, p = 0.84, respectively). CONCLUSION/CONCLUSIONS:Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible.

Viruses are implicated in the initiation or flare of graft-versus-host disease (GVHD) by virtue of their ability to activate antigen-presenting dendritic cells (DC). Herpes simplex virus (HSV) infects circulating CD34+ stem cell progenitors, favoring their differentiation into skin homing DC (CD1a+ Langerhans cells) that contribute to the development of an inflammatory skin rash known as HSV-associated erythema multiforme (HAEM). Following on these findings, we conducted a prospective study to examine whether HSV is also associated with GVHD. Skin biopsies and peripheral blood mononuclear cells (PBMC) were collected from 37 consecutive patients on admission before and after allogeneic hematopoietic stem cell transplantation (HSCT) and examined for HSV antigen (Pol) expression and the presence of Pol+CD34+ and Pol+CD1a+ cells. Sixteen patients developed a skin rash that was histopathologically consistent with GVHD (group I), 3 patients had a rash that was not GVHD (group II, EM-like) and 18 patients did not develop any rash after HSCT (group III). Skin biopsies from the group I patients were Pol negative pre-HSCT (baseline) but became Pol+ after the diagnosis of GVHD. The GVHD biopsies also contained Pol+CD34+ and Pol+CD1a+ cells, and these patients had a significant percentage of circulating Pol+CD34+ and Pol+CD1a+ PBMC. By contrast, the group II patients had Pol+ skin cells and Pol+CD34+ circulating PBMC at baseline that decreased post-HSCT. The group III patients had Pol negative skin and very few circulating Pol+CD34+ and Pol+CD1a+ PBMC at baseline that were not significantly changed post-HSCT. The data associate skin GVHD with HSV reactivation during conditioning and its propensity for nonreplicative infection of CD34+ PBMC that induces DC activation. Further studies are needed to better elucidate this association.

We present a case of a 64-year-old man with refractory acute myeloid leukemia and trisomy 8 who developed leukemia cutis. Interphase fluorescence in situ hybridization (FISH) was performed on a paraffin-embedded skin section. FISH confirmed a population of cells with trisomy 8 in the blastic infiltrates involving the skin. This case illustrates a novel application of interphase FISH to confirm the diagnosis of leukemia cutis.

BACKGROUND:Mutation in the folliculin gene in Birt-Hogg-Dubé (BHD) syndrome leads to a spectrum of benign tumors of the hair follicle, classically including both fibrofolliculoma and trichodiscoma. In addition, lesions clinically indistinguishable from fibrofolliculoma/ trichodiscoma may show histopathologic findings of perifollicular fibroma or angiofibroma. Although some consider perifollicular fibroma to be a variant of angiofibroma, the specific histopathologic findings of perifollicular fibroma are uncommon. METHODS:This is a case series. RESULTS:In 4 patients with multiple facial lesions, recognizing perifollicular fibroma would have been helpful in leading to the diagnosis of BHD syndrome. CONCLUSION/CONCLUSIONS:Perifollicular fibroma is on a spectrum with fibrofolliculoma and trichodiscoma; in a patient with multiple lesions, the diagnosis of perifollicular fibroma is suggestive of BHD syndrome.

Progress in the treatment of non-small-cell lung cancer (NSCLC) will require the introduction of new agents as well as better use of existing therapies. Targeted therapies are likely to have a profound effect on the treatment of NSCLC after identification of patients who are most likely to benefit. The epothilones are novel anti-tubulin agents derived from Sorangium cellulosum. β III tubulin overexpression has been implicated as a mechanism of anti-tubulin resistance that can be overcome by epothilones. Several epothilones have advanced to clinical trials; ixabepilone (BMS247550, aza-epothilone B, Bristol-Myers Squibb, New York, NY), patupilone (EPO906, Novartis, Basel, Switzerland) and sagopilone (ZK-EPO, ZK-219477, Schering AG, Berlin-Wedding, Germany) are currently in active development. Several of the epothilones, most notably ixabepilone, have demonstrated activity in lung cancer in phase I and II trials, including taxane-resistant patients. Although a phase II study failed to show superior outcome in patients with β III tubulin overexpression, other aspects of the epothilones argue for their continued development.