Keira L. Barr

Rare Tumors Through the Looking Glass: An Examination of Malignant Cutaneous Adnexal Tumors

OBJECTIVE To identify prognostic factors related to malignant cutaneous adnexal tumors. DESIGN Population-based study using the Surveillance, Epidemiology, and End Results database from January 1, 1988, through December 31, 2006. SETTING Seventeen population-based cancer registries. PARTICIPANTS A total of 4032 patients with malignant cutaneous adnexal tumors. MAIN OUTCOME MEASURES Overall survival (OS) and disease-specific survival (DSS). RESULTS Ten-year OS and DSS rates were 54% and 97%, respectively. Unfavorable factors for OS were increasing age (hazard ratio [HR] 1.08; 95% confidence interval [CI], 1.07-1.09; P < .001), distant metastases (3.26; 2.34-4.53; P < .001), no surgical procedure (1.27; 1.01-1.59; P = .04), grade IV tumors (1.97; 1.18-3.28; P = .009), nodal metastases (2.19; 1.40-3.43; P = .001), and T3 tumors (1.37; 1.00-1.87; P = .04). Favorable factors for OS were a wide surgical excision (HR, 0.78; 95% CI, 0.68-0.89; P < .001), female sex (0.73; 0.65-0.82; P < .001), malignant eccrine spiradenoma (0.72; 0.53-0.99; P = .04), and histologic findings of sweat duct carcinoma (0.63; 0.44-0.90; P = .01). Unfavorable factors for DSS included N1 status (HR, 6.77; 95% CI, 2.11-21.68; P < .001), distant metastases (12.24; 6.03-24.85; P < .001), histologic findings of malignant eccrine spiradenoma (5.62; 1.25-25.34; P = .02), and no surgical procedure (2.81; 1.09-7.23; P = .03). Favorable factors for DSS included female sex (HR, 0.52; 95% CI, 0.30-0.91; P = .02). CONCLUSIONS Five-year survival among patients with malignant cutaneous adnexal tumors is good in the absence of distant metastases. Wide resection may be preferable to less aggressive excision. The prognostic importance of lymph node metastases warrants consideration of lymph node basin staging.

Assessment of the ‘no eosinophils' rule: are eosinophils truly absent in pityriasis lichenoides, connective tissue disease, and graft‐vs.‐host disease?

Eosinophils are often present in the inflammatory infiltrate of an interface dermatitis, but the diagnostic specificity of eosinophils in interface dermatitis has not been formally evaluated. We retrospectively identified 97 examples of interface dermatitis with clinically confirmed diagnoses, including lupus erythematosus (LE), lichen planus, pityriasis lichenoides (PL), graft‐vs.‐host disease (GVHD), dermatomyositis (DM) and drug reaction. Diagnoses were clinically confirmed by at least two dermatologists. Slides were reviewed in a blinded fashion by at least two dermatopathologists. The average eosinophil count per 10 ×200 (×20 objective) fields was lowest for PL (0.2), DM (0.3), GVHD (0.4), and LE (0.5) [defined as Group 1] and was higher for lichen planus, drug reactions, erythema multiforme (major and minor) and viral exanthems [defined as Group 2]. Distinction between Group 1 and Group 2 was maximized using an eosinophil count cutoff of 1.1. In conclusion, eosinophils are usually rare to absent in PL, DM, most forms of LE and GVHD. While final interpretation requires a composite assessment of all features, our results suggest that the presence of even a single eosinophil within nine or ten ×20 fields argues against a diagnosis of PL, DM or LE.

Nonbullous neutrophilic dermatosis: Sweet’s syndrome, neonatal lupus erythematosus, or both?

We describe a 5-day-old infant who fulfilled the diagnostic criteria for Sweet’s syndrome, and the concurrent histologic and autoantibody features supporting the diagnosis of neonatal lupus. To our knowledge, this is the youngest case of Sweet’s syndrome reported in the literature. Importantly, our findings further support the hypothesis that lupus erythematosus should be considered in the differential diagnosis of a nonbullous neutrophilic dermatosis, as it may represent the initial manifestation of the disease.

Pyoderma gangrenosum masquerading as necrotizing fasciitis

Necrotizing fasciitis is a fulminant advancing soft tissue infection characterized by widespread fascial necrosis, which can result in significant morbidity and even death. This condition requires prompt diagnosis and aggressive management with extensive surgical debridement and appropriate antibiotic coverage. Pyoderma gangrenosum, in contrast, is a noninfectious inflammatory condition of the skin that typically does not require surgical management. Both conditions can present with extensive ulceration and tissue necrosis, and close clinical-pathologic correlation is required to make the appropriate diagnosis. We present a case in which the diagnosis of pyoderma gangrenosum was initially elusive and serves to illuminate the diagnostic pitfalls in dealing with these entities.

Surgeon error and slide quality during Mohs micrographic surgery: Is there a relationship with tumor recurrence?

BACKGROUND Recurrences after Mohs micrographic surgery (MMS) have been associated in the past with aggressive tumor type, large tumor size, and location within certain anatomic subunits. These factors are beyond the control of the treating physician and not subject to quality improvement efforts. OBJECTIVE We sought to determine the relationship between slide quality and surgeon error with tumor recurrence after MMS. METHODS This case-control study compared slide characteristics from 19 recurrent cancers previously treated using MMS with 95 nonrecurrent controls. The controls were randomly selected from a database of 6208 MMS cases from the University of California, Davis, from 2002 to 2009. RESULTS Significant factors for recurrences using χ(2) or Fisher exact tests included: tumor type, surgeon error, tissue drop out, dense inflammation, aggressive tumor subtype, and surgeries with 3 or more layers. After multivariate analysis with a stepwise regression model, factors that remained significant included surgeon error, tissue drop out, and aggressive tumor subtype. LIMITATIONS The study involved only 2 surgeons and was from a single center. Not all recurrences were likely identified. CONCLUSIONS Surgeon errors resulting in persistent unexcised tumor were strongly associated with tumor recurrence. Tissue drop out and aggressive tumor subtype were also important factors. Two of these factors are within the control of the treating physician, and thus potentially improvable.

Elastin staining patterns in primary cicatricial alopecia.

BACKGROUND Most biopsy specimens of cicatricial (scarring) alopecia can be readily subclassified as lymphocytic versus neutrophilic, but specific diagnosis remains difficult, particularly when a late stage of the disease is sampled. OBJECTIVE We sought to document patterns of scarring highlighted by elastic tissue staining in primary cicatricial alopecia. METHODS We documented Verhoeff elastic van Gieson staining patterns in 58 routinely embedded (vertical) biopsy specimens of cicatricial alopecia. Patterns of fibrosis included perifollicular (wedge-shaped vs broad tree trunk-shaped) and diffuse. The patterns were compared against the diagnosis obtained by independent expert clinical review, including central centrifugal cicatricial alopecia (CCCA), lichen planopilaris, traction alopecia, frontal fibrosing alopecia, discoid lupus erythematosus, and tufted folliculitis. RESULTS Wedge-shaped perifollicular fibrosis was seen in lichen planopilaris but also in CCCA. Broad tree trunk-shaped perifollicular fibrosis was most commonly encountered in CCCA. LIMITATIONS The retrospective nature of the study precluded temporal staging of the disease process. CONCLUSIONS Patterns of fibrosis highlighted by elastin staining in primary cicatricial alopecia appear to be disease specific. Superficial wedge-shaped perifollicular fibrosis is associated with but may not be specific for lichen planopilaris. Broad tree trunk-like perifollicular fibrosis is specific for CCCA but not present in many cases. Elastin staining represents a useful ancillary study for the evaluation of late-stage scarring alopecia in routinely oriented punch biopsy specimens.

Current Knowledge in Inflammatory Dermatopathology

The complex and fascinating spectrum of inflammatory skin disease, and the comprehension of it, is ever expanding and evolving. During the first decade of the 21st century, numerous advances in the understanding of inflammatory disease mechanisms have occurred, particularly in psoriasis and atopic dermatitis. Continuation of this trend will assure a future in which molecular tests for biomarkers of immediate clinical relevance are used in routine patient care, not only for diagnosis but also for prognosis and management. This article focuses on selected recent or noteworthy developments that are clinically relevant for the histologic diagnosis of inflammatory skin diseases.

Lupus erythematosus-like imiquimod reaction: A diagnostic pitfall

Imiquimod (AldaraTM), a Toll‐like receptor 7 agonist (TLR7), is known for its unique properties of being an immune response modifier and stimulator. Upon topical application, this TLR7 agonist triggers a cell‐mediated immune response predominantly expressed by dendritic cells and monocytes. Local skin irritation at the application site involving erythema, pain, crusting and erosions is common and well documented. On the contrary, the specific histopathologic features associated with these treatment site reactions is not. Herein reported is a case where historical omission of imiquimod use for actinic keratosis complicated the histologic interpretation. We highlight a lupus erythematosus‐like microscopic pattern and explore histopathologic features that could help in avoiding a diagnostic pitfall, as well as the relationship between TLR activation, cell‐mediated immunity and skin histology.

Signet ring cell melanoma, Brenner sign, and elevated vascular endothelial growth factor

few of the reported cases with drug-induced BP have been confirmed by a rechallenge or a positive patch test. We think that the interventions in our patient could be considered as a successful rechallenge with aspirin. Several mechanisms have been postulated for the pathogenesis of drug-induced BP. Sulfhydrylcontaining drugs may lead to direct dermoepidermal splitting with or without antibodies; however, aspirin does not contain this group. Some BP-inducing drugs, such as penicillamine, decrease suppressor T-cell activity, which stimulates the hyperproduction of autoantibodies against the BP antigens. By altering the antigenicity of the lamina lucida or attaching to a cell site, certain drugs may also act as a hapten and lead to the formation of autoantibodies. Aspirin may have acted as a hapten in our patient. Our case indicates a causal relationship between aspirin, probably the most widely used drug in the world, and BP.

Subcutaneous nodule on the left hand: challenge.

REPORT OF A CASE A 63-year-old man was referred to the Department of Plastic and Reconstructive Surgery at the Mather VA Medical Center for excision of a subcutaneous nodule on the left thenar eminence. The nodule was reportedly present for approximately 6 months before presentation. Pertinent history included his occupation in the construction industry, which required heavy usage of his hands. He denied a history of antecedent trauma. He complained of tenderness on movement of the left thumb and on palpation of the nodule. On physical examination, the lesion was described as a firm 1.3-cm nodule that was adherent to the overlying skin. No mention was made of puckering or dimpling of skin on manipulation. Of note, however, the lesion was tender on palpation. Incidentally, the patient was also found to have a weak abductor pollicis brevis muscle along with some numbness of the left hand, in both the median and ulnar nerve distributions. However, he could spread his fingers with adequate strength. Patient attributed the neurological finding to prior left upper arm trauma unrelated to onset of this lesion. The preliminary clinical differential diagnosis included a ganglion cyst and epidermoid inclusion cyst. The nodule was excised, and the specimen was sent to our dermatopathology service for diagnostic consultation. A preoperative clinical photograph was not taken by the surgeon. Following is the histological low-power and high-power views of the lesion (Figs. 1, 2).