Using global gene expression to discriminate thin melanomas with poor outcomes.

Most melanomas present as thin lesions (≤1.0 mm) with a good prognosis; however, a small percentage of patients with thin lesions experience recurrence or metastasis. The aim of our study was to identify a distinct pattern of gene expression within thin melanomas known to have eventually metastasized to regional lymph nodes or distant sites compared with those that followed the typical course with good response to wide local excision alone. Patients who were disease-free for a minimum of 10 y served as controls (n = 10) to the experimental group who developed metastasis (n = 9). Laser capture microdissection was used to specifically isolate cancer cells from formalin-fixed paraffin-embedded tissue with subsequent gene expression analysis on Affymetrix Human Transcriptome Array 2.0 Arrays. Although gene expression differences were observed between the patients with thin melanoma with poor clinical outcome and those with good clinical outcome, neither the number of genes nor the magnitude of the fold difference was very substantial or significant. Cluster analysis with this subset of genes could definitively separate a subset of the poor responders from the good responders, but there remained a mixed group of tumors that could not be predicted from gene expression alone. Pathway analysis identified cellular processes that were regulated based on the response, including categories commonly associated with melanoma progression. Ultimately, we concluded that there were very few differences between these groups. Future research will be required and investigation of the mutational landscape may be another strategy to uncover genomic changes that drive recurrence and metastasis in thin melanoma.

A malignant cutaneous neuroendocrine tumor with features of Merkel cell carcinoma and differentiating neuroblastoma.

We report an unusual primary cutaneous neuroendocrine carcinoma that shows histologic and immunohistochemical features of ganglioneuroblastoma/differentiating neuroblastoma. The neoplasm is composed predominantly of small atypical neoplastic cells embedded in distinct clusters of immature and mature ganglion cells with associated neuropil. The neoplastic cells show strong perinuclear staining for cytokeratin 20 (CK20) with a dot-like pattern, supporting our contention that this is an unusual variant of Merkel cell carcinoma. To the best of our knowledge, ganglioneuroblastoma-like differentiation has not been previously described in Merkel cell carcinoma.

Detection of HHV-8 in pyogenic granuloma-like Kaposi sarcoma.

Kaposi sarcoma (KS) is a low-grade vascular neoplasm associated with human herpesvirus-8 (HHV-8) infection. Clinically, lesions commence as blue-red macules that may develop into plaques and eventually into nodules. The histologic appearance spans a broad spectrum and varies with the stage of the lesion. At each stage, KS has significant morphologic overlap with other vasoproliferative lesions. Recently, we encountered 6 KS tumors that histologically mimicked pyogenic granuloma (PG), a common benign vascular tumor of the skin that usually does not figure in the histologic differential diagnosis of KS. We stained 6 PG-like KS and 28 PGs with a mouse monoclonal antibody (13B10) against HHV-8 latent nuclear antigen-1 (LNA-1) to determine the utility of immunoperoxidase staining in distinguishing KS from PG. All 6 PG-like KS demonstrated nuclear staining for HHV-8 LNA-1. No staining was identified in any of the 28 PGs. Histologic criteria often used to differentiate between these two entities were not helpful in our cases. The only distinguishing feature was the presence or absence of HHV-8 LNA-1 staining. The presence of HHV-8 LNA-1 nuclear staining seems to be a specific marker for KS when comparing PGs and PG-like KS. Immunoperoxidase staining for HHV-8 LNA-1 is a useful diagnostic tool in this setting.

Sentinel lymph node biopsy for cutaneous melanoma: the Stanford experience, 1997-2004.

OBJECTIVE: To review sentinel lymph node (SLN) data from Stanford University Medical Center from January 1, 1997, to January 1, 2004, including rates of SLN positivity according to 2002 American Joint Committee on Cancer (AJCC) tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence. DESIGN: Retrospective case series. SETTING: Stanford University Medical Center and Stanford melanoma clinics. PATIENTS: A total of 274 consecutive patients with primary melanoma who underwent SLN biopsy (SLNB) between January 1, 1997, and January 1, 2004, or who were referred to the Stanford melanoma clinics after SLNB and were followed up through March 2005. INTERVENTIONS: All patients underwent standard wide local excision of their primary tumors and SLNB with intradermal injection of isosulfan blue dye and/or technetium sulfur colloid. MAIN OUTCOME MEASURE: Rates of SLN positivity per 2002 AJCC tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence in node-negative and node-positive patients. RESULTS: Positive SLNs were detected in 39 (15%) of 260 cases, including 0 (0%) of 45 for cutaneous melanomas 1.0 mm thick or less (T1), 21 (18%) of 115 for melanomas 1.01 to 2.0 mm thick (T2), 12 (19%) of 64 for melanomas 2.01 to 4.0 mm thick (T3), and 5 (16%) of 32 for melanomas thicker than 4.0 mm (T4). Median Breslow depths were 1.89 mm for SLN-positive biopsy specimens and 1.50 mm for SLN-negative biopsy specimens (P = .07). The recurrence rate was 46% among SLN-positive patients, with a median time to recurrence of 8 months. Bivariate analysis revealed SLN positivity to be associated with AJCC tumor classification (P = .02), location on the trunk (P = .03), and presence of ulceration (P = .03). By multivariate logistic regression, ulceration (P = .01) was predictive of SLN positivity, whereas SLN status (P< .001), ulceration (P = .02), and location (P = .03) were predictive of recurrent disease. CONCLUSION: Data from the past 8 years confirm the accuracy and prognostic value of SLNB in cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative patients.

Autoantibody formation after alloimmunization: are blood transfusions a risk factor for autoimmune hemolytic anemia?

BACKGROUND: The development of RBC autoantibodies resulting from or associated with allogeneic blood transfusions (i.e., RBC autoimmunization) is not a well-recognized complication of RBC transfusions. STUDY DESIGN AND METHODS: T: he presentation, laboratory evaluation, clinical course, and management of two patients whose autoimmune hemolytic anemia followed allogeneic blood transfusion and occurred in association with the development of one or more alloantibodies is described. A retrospective analysis was performed of our blood-bank records over 1 year to determine the frequency of RBC autoimmunization associated with alloimmunization. RESULTS: Out of 2618 patients who had a positive DAT or IAT, 121 were identified with RBC autoantibodies; 41 of these patients had both allo- and autoantibodies to RBC antigens, whereas the remainder, 80, had only autoantibodies. At least 34 percent (12/41) of these patients (none with hemoglobinopathy) developed their autoantibodies in temporal association with alloimmunization after recent blood transfusion(s). CONCLUSION: RBC autoimmunization and the development of autoimmune hemolytic anemia should be recognized as a complication of allogeneic blood transfusion. The need for additional blood transfusion was successfully avoided in one patient by treatment with recombinant human EPO and corticosteroid therapy. Once RBC autoimmunization is identified, subsequent management should incorporate a strategy that minimizes subsequent exposure to allogeneic blood.

WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas.

WT1 diffusely stains most ovarian serous carcinomas; reactivity of uterine papillary serous carcinomas has not been evaluated. We studied WT1 expression in 13 International Federation of Gynecology and Obstetrics stage 1 and 5 stage 3 or 4 uterine papillary serous carcinomas without ovarian metastases and compared their reactivity with the WT1 staining of 30 ovarian serous carcinomas. WT1 reactivity was evaluated with the C19 and 6F-H2 antibody clones. All 18 uterine papillary serous carcinomas were nonreactive for WT1. The nonovarian metastases of the 5 high-stage uterine papillary serous carcinomas also were nonreactive for WT1. In contrast, 29 (97%) of 30 ovarian serous carcinomas were reactive for WT1. WT1 reactivity in an unknown primary serous carcinoma would suggest it is from a nonuterine site. The mechanisms underlying these findings are unknown. They raise the possibility of genetic differences between the 2 morphologically similar neoplasms.