Clinicopathological and Molecular Features of Penile Melanoma With a Proposed Staging System.

Penile melanomas (PM) are an exceedingly rare subtype of mucosal melanoma (MM), and we reviewed the clinicopathologic features and molecular profile in 8 PMs. The patient ages ranged from 46 to 78 (mean: 62.8) years with involvement on the glans (n=5; 62.5%), penile urethra (n=2; 25%), and foreskin (n=1, 12.5%). Tumor depth ranged from 1.6 to 10.0 (mean: 5.25) mm. Most of the patients underwent partial penectomy (n=6; 75%) and sentinel lymph node (LN) biopsy N=7; 87.5%). Seven patients had metastatic disease at diagnosis, 6 involving LNs and 1 the adrenal gland, and 4 died of disease with a mean follow-up period of 40.5 (2 to 95) months. Five of 7 (71%) cases identified 15 molecular alterations within KIT, CDKN2A, NF1, PTEN, and APC (n=2 each), and NRAS, MAP3K1, CDH1, MSH6, and TERT (n=1 each). Two cases were not found to harbor genetic aberrations, and 1 case failed testing. In addition, we reviewed the English literature and included 93 cases with a reported depth of invasion and follow-up. A total of 101 PMs were analyzed for prognostic parameters, and the overall survival was significantly worse in patients with LN metastasis (P=0.0008), distant metastasis (P=0.0016), and greater depth of invasion (P=0.0222) based upon T-stage. While T4 conferred substantially worse survival, the delineation of the survival curves between T2 and T3 was less clear, and combining T2+T3 disease had a strong prognostic impact (P=0.0024). Prognostic parameters used in the staging of cutaneous melanomas may also be used in PMs. An alternative staging system expanding the inclusion criteria for T2 might provide a more accurate prognostic stratification.

Disseminated cryptococcosis with cutaneous manifestation.

Cutaneous cryptococcosis is uncommon. It is usually a result of disseminated infection and can present with a wide variety of skin lesions. We report a case of disseminated cryptococcosis in a kidney transplant recipient who presented with nodular lesions in the forehead following a bout of acute cellular rejection.

Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year cohort study.

OBJECTIVE: To identify factors associated with poor outcomes in perineurally invasive squamous cell carcinoma. DESIGN: Retrospective cohort study. SETTING: Two academic hospitals in Boston, Massachusetts. PATIENTS: Adults with perineural SCC diagnosed from 1998 to 2008. MAIN OUTCOME MEASURES: Hazard ratios (HRs) for local recurrence, nodal metastasis, death from disease, and overall death, adjusted for known prognostic factors. RESULTS: A total of 114 cases were included, all but 2 involving unnamed nerves. Only a single local recurrence occurred in cases with no risk factors other than nerve invasion. Tumors with large nerve (≥ 0.1 mm in caliber) invasion were significantly more likely to have other risk factors, including diameters of 2 cm or greater (P<.001), invasion beyond the subcutaneous fat (P<.003), multiple nerve involvement (P<.001), infiltrative growth (P=.01), or lymphovascular invasion (P=.01). On univariate analysis, large nerve invasion was associated with increased risk of nodal metastasis (HR, 5.6 [95% CI, 1.1-27.9]) and death from disease (HR, 4.5 [95% CI, 1.2-17.0]). On multivariate analysis, tumor diameter of 2 cm or greater predicted local recurrence (HR, 4.8 [95% CI, 1.8-12.7]), >1 risk factor predicted nodal metastasis (2 factors: HR, 4.1 [95% CI, 1.0-16.6]), lymphovascular invasion predicted death from disease (HR, 15.3 [95% CI, 3.7-62.8]), and overall death (HR, 1.1 [95% CI, 1.0-1.1]). Invasion beyond subcutaneous fat also predicted overall death (HR, 2.1 [95% CI, 1.0-4.3]). CONCLUSIONS: Squamous cell carcinoma involving unnamed small nerves (<0.1 mm in caliber) may have a low risk of poor outcomes in the absence of other risk factors. Large-caliber nerve invasion is associated with an elevated risk of nodal metastasis and death, but this is due in part to multiple other risk factors associated with large-caliber nerve invasion. A larger study is needed to estimate the specific prognostic impact of nerve caliber.

Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases.

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process.

Facial nerve hemangiomas: vascular tumors or malformations?

OBJECTIVE: To reclassify facial nerve hemangiomas in the context of presently accepted vascular lesion nomenclature by examining histology and immunohistochemical markers. STUDY DESIGN: Cohort analysis of patients diagnosed with a facial nerve hemangioma between 1990 and 2008. SETTING: Collaborative analysis at a specialty hospital and a major academic hospital. SUBJECTS AND METHODS: Seven subjects were identified on composite review of office charts, a pathology database spanning both institutions, and an encrypted patient registry. Clinical data were compiled, and hematoxylin-eosin-stained specimens were reviewed. For six patients, archived pathological tissue was available for immunohistochemical evaluation of markers specific for infantile hemangioma (glucose transporter protein isoform 1 [GLUT1] and Lewis Y antigen) and for lymphatic endothelial cells (podoplanin). RESULTS: All patients clinically presented with slowly progressive facial weakness at a mean age of 45 years without prior symptomatology. Hemotoxylin-eosin-stained histopathological slides showed irregularly shaped, dilated lesional vessels with flattened endothelial cells, scant smooth muscle, and no internal elastic lamina. Both podoplanin staining for lymphatic endothelial cells and GLUT1 and LewisY antigen staining for infantile hemangioma endothelial cells were negative in lesional vessels in all specimens for which immunohistochemical analysis was performed. CONCLUSION: Lesions of the geniculate ganglion historically referred to as "hemangiomas" do not demonstrate clinical, histopathological, or immunohistochemical features consistent with a benign vascular tumor, but instead are consistent with venous malformation. We propose that these lesions be classified as "venous vascular malformations of the facial nerve." This nomenclature should more accurately predict clinical behavior and guide therapeutic interventions.

Juvenile conjunctival nevus: clinicopathologic analysis of 33 cases.

Conjunctival nevi in children and adolescents often have histologic features that can be difficult to differentiate from malignancy. We have identified a subset of childhood nevi displaying a confluent growth pattern and a lack of maturation that we have defined as juvenile conjunctival nevi (JCN), with the aim of further describing the clinicopathologic features of these lesions. Lesions identified as conjunctival nevus in a tertiary referral hospital were reviewed and the subset of lesions identified as JCN were further evaluated. Clinical details including follow-up data were also gathered. Of the 40 conjunctival nevi identified, 33 fit the criteria for JCN. The mean age at time of excision was 10.9 years (range: 4 to 19 y). Thirty-two lesions were of the compound type; one was a junctional nevus. All showed a nested junctional growth pattern. In 17 lesions (61%), the junctional component extended beyond the subepithelial component (shoulder phenomenon). Maturation was absent in 21 of the compound nevi (66%, average age 10.3 y), and incomplete in the remaining 11 lesions (34%, average age 12.1 y). The nuclei of the subepithelial nevus cells were larger than the epithelial nevus cells in 19 nevi (59%) and the same size in 13 (41%). A lymphocytic host response was present in 17 lesions (52%). Mitotic figures were rarely seen. None of the lesions had recurred over an average follow-up period of 34 months. Recognition of JCN as a distinct morphologic variant of a conjunctival nevus with characteristic histologic features may help to distinguish this benign lesion from melanoma.