Current controversies in early-stage melanoma: Questions on incidence, screening, and histologic regression.

In the first article in this continuing medical education series we review controversies and uncertainties relating to the epidemiology and initial diagnosis of localized cutaneous melanoma (ie, stage 0, I, or II). Many of these issues are unsettled because of conflicting evidence. Melanoma incidence appears to be increasing, yet its basis has not been fully explained. Despite the advantages of early detection, the US Preventive Services Task Force does not recommend skin screening for the general population. Occasionally, biopsy specimens of melanoma will show histologic regression, but the prognostic importance of this phenomenon is uncertain. Some practitioners recommend obtaining a sentinel lymph node biopsy specimen for thin melanomas showing regression, although this histologic finding is not part of the staging system for thin melanomas. Our goal is to provide the clinician who cares for patients with (or at risk for) melanoma with up-to-date contextual knowledge to appreciate the multiple sides of each controversy so that they will be better informed to discuss these issues with their patients and their families.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis.

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. A total of 123 patients with BM were matched by initial presenting stage to 237 patients without BM. The characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020), and Breslow depth more than 4 mm (P=0.048), whereas location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, P=0.007) than nonscalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in the clinical outcomes between patients whose BM were detected upon routine screening versus those detected upon symptomatic presentation. In summary, factors predictive of development of BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type, and ulceration, but not detection setting, were associated with worse clinical outcomes.

Histiocytic sarcoma with secondary involvement of the skin and expression of CD1a: evidence of indeterminate cell differentiation?

BACKGROUND: Histiocytic sarcoma is an exceedingly rare malignant neoplasm composed of cells with a monocyte/macrophage phenotype. In the current nosology of histiocytic neoplasms, histiocytic sarcoma is separate from indeterminate cell histiocytosis, a generally benign disorder characterized by proliferation of a CD1a+ and S-100+ population of cells lacking Birbeck granules usually limited to the skin. METHODS: We present a case of histiocytic sarcoma in a 64-year-old man presenting as a peritonsillar mass and secondarily involving the skin. RESULTS: The malignant cells in the extracutaneous foci of disease expressed macrophage-associated antigens including S-100 but were CD1a-. The malignant cells in the skin coexpressed CD1a and S-100 but lacked ultrastructural features of Langerhans cells, findings indicative of indeterminate cells. CONCLUSIONS: We discuss the clinical and histopathologic differential diagnosis in association with prior reported cases of histiocytic sarcoma, particularly in cases involving the skin and cases expressing the Langerhans cell-associated antigen CD1a.

Ewing sarcoma/peripheral primitive neuroectodermal tumor: adult abdominal tumors with an Ewing sarcoma gene rearrangement demonstrated by fluorescence in situ hybridization in paraffin sections.

The differential diagnosis of small round cell tumors is exhaustive and requires ancillary studies. Relatively recently, fluorescence in situ hybridization (FISH) using probes for specific gene rearrangements has gained wide acceptance. This technique is particularly useful in the differential diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) and desmoplastic small round-cell tumor (DSRCT). In ES/PNET, the EWS gene is juxtaposed to the FLI-1 gene in 85% of cases and to the ERG gene in another 7% of cases; the EWS gene is juxtaposed to the WTI gene in DSRCT. Documentation of the EWS gene rearrangements in EWS/PNET has previously been demonstrated in frozen tissue. We report 2 unusual cases of EWS/PNET diagnosed in abdominal tumors in adults. Although the immunohistochemical results supported a diagnosis of ES/PNET, 1 case morphologically resembled DSRCT. The diagnosis in these 2 cases was confirmed by the FISH demonstration of EWS/FLI-1 gene fusion in paraffin-embedded tissue. Thus, the usefulness of FISH demonstration of an EWS gene rearrangement with these specific probes in such unusual cases is supported and is demonstrated in paraffin-embedded tissue.

Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.

Flow cytometric immunophenotyping in posttransplant lymphoproliferative disorders.

We studied the flow cytometric immunophenotyping (FCI) and genotypic data of 11 specimens from 10 transplant recipients and categorized them based on a scheme for posttransplant lymphoproliferative disorders (PTLDs). Specimens had been analyzed by polymerase chain reaction and/or Southern blot for T-cell and B-cell (immunoglobulin heavy chain and light chain genes) gene rearrangements (BGR). The categories for PTLDs were as follows: 1, 1; 2, 6; and 3, 4. The plasmacytic and polymorphic B-cell hyperplasias (PBCHs) revealed no monoclonal/aberrant cells by FCI or genotypic studies (GS). Three of 4 polymorphic B-cell lymphomas (PBCLs) revealed monoclonal or aberrant (no surface light chain) B cells by FCI; 1 of 3 revealed a BGR. However, the 1 case with no monoclonal/aberrant B cells by FCI revealed a BGR. Both immunoblastic lymphomas revealed monoclonal or aberrant B cells by FCI; 1 revealed a BGR. Both multiple myelomas revealed monoclonal plasma cells by FCI; 1 revealed a BGR. In the 4 PTLDs with monoclonal/aberrant B cells by FCI and no clonality detected by GS, the GS were performed on fresh and paraffin-embedded tissue samples. FCI of the plasmacytic and PBCHs supported no clonal process by GS. FCI defined a clonal process in 2 PBCLs, I immunoblastic lymphoma, and 1 multiple myeloma that were negative by GS. However, 1 PBCL that was polyclonal by FCI was monoclonal by GS. Thus, FCI is useful for identifying a clonal process in PTLDs with negative results by GS; FCI and GS should be performed routinely in PTLDs to detect a clonal process.