Gabriel C. Caponetti

Kaposi sarcoma (KS) of bone and skeletal muscle is unusual. In this report, the authors review 66 published patients with KS who had involvement of the musculoskeletal system reported from 1925 to 2006. In only 3 patients was acquired immunodeficiency syndrome (AIDS)-related KS identified within skeletal muscle. Osseous KS lesions were more frequent and occurred with African, classic, and AIDS-related KS and occurred rarely in transplantation-associated KS. Patients seldom were asymptomatic. They usually had bone pain with limited mobility or infrequently developed serious sequelae like spinal cord compression. Locally aggressive African and classic KS lesions typically involved the peripheral skeleton; whereas, in patients with AIDS, the axial (vertebrae, ribs, sternum, and pelvis) and/or maxillofacial bones more commonly were involved. Almost all patients had concomitant nonosseous KS lesions. Joint involvement was exceptional, and pathologic fractures were not observed. Computed tomography scans and magnetic resonance images were better at detecting osseous KS lesions, which frequently went undetected on plain x-ray films or bone scans. Pathologic diagnosis was important to exclude similar lesions like bacillary angiomatosis. Treatment options, including surgery and, in more recent patients, radiation and/or chemotherapy, had limited success.

Cat-scratch disease (CSD) is largely due to infection with Bartonella henselae. Microbiologic detection is difficult, and molecular testing is not readily available. A monoclonal antibody (mAB) to B henselae has become commercially available. We evaluated the usefulness of immunohistochemical analysis (IHC) for diagnosing CSD on surgical specimens and compared these results with polymerase chain reaction (PCR) detection and serologic testing for B henselae. We studied 24 formalin-fixed, paraffin-embedded (FFPE) cases of lymphadenitis with histologic and/or clinical suspicion of CSD. Control cases included 14 cases of lymphadenopathy other than CSD. FFPE tissue sections were evaluated with an mAB to B henselae, Steiner silver stain (SSS), and PCR that targeted B henselae and Bartonella quintana. Positive cases were as follows: SSS, 11 (46%); PCR, 9 (38%); and IHC, 6 (25%). Only 2 cases (8%) were positive for all 3 studies. All control cases were negative for IHC and PCR. The diagnostic sensitivity of these 3 tests is low for CSD. SSS seems to be the most sensitive test but is the least specific. PCR is more sensitive than IHC and may, therefore, serve as a helpful second-line test on all IHC- cases.

BACKGROUND: Merkel cell carcinoma is a rare and aggressive neoplasm originating from mechanoreceptor Merkel cells of the stratum basale of the epidermis. Cases affecting the vulva are exceedingly rare, with the currently available literature primarily in case report form. BODY: Systematic review of the PubMed database returned 17 cases of Merkel cell carcinoma affecting the vulva. Patients presented at a mean age of 59.6 years with a firm, mobile vulvar mass. Symptoms of pain, erythema, pruritus, edema, and ulceration have been reported. Tumor histology is consistent with that of neuroendocrine tumors and typical Merkel cell carcinomas. Neuroendocrine and cytokeratin immunostains are frequently utilized in histopathological workup. Surgical management was the unanimous first-line therapy with adjuvant radiation in most cases. Recurrence occurred in 70.6% of patients at a mean follow-up of 6.3 months. Mortality was at 47.0% at a mean of 7.8 months after initial operation. CONCLUSION: Merkel cell carcinoma affecting the vulva is an extremely rare and highly aggressive neoplasm. The present review of published cases serves to comprehensively describe the clinical course and treatment approaches for vulvar Merkel cell carcinoma.

Abstract Abstract 288 This is phase I/II trial designed to evaluate the safety and clinical activity of Dasatinib, a potent, broad spectrum inhibitor of 5 critical oncogenic tyrosine kinase families: BCR-ABL, SRC, c-KIT, PDGF receptors (α and β) and ephrin (EPH) receptor kinases, in NHL. The primary end point was maximum tolerable dose (MTD) of dasatinib in the phase I stage and overall response rate (ORR) in phase II stage of the study. Eligible patients must be at least 19 y/o with relapsed or refractory NHL after at least one prior systemic therapy, ECOG performance status 0–2, and able to take oral medications. The Phase I trial utilized a 3+3 design where patients received Dasatinib once daily for 28 day cycles in one of 3 dose cohorts (100, 150, 200 mg daily). Patients continued on Dasatinib until disease progression. NCI grade IV non-hematological toxicity defined dose-limiting toxicity (DLT) in phase I. The phase II stage used a two-stage design. Patients who are in complete or partial remission (CR or PR) after one cycle were considered responders. The study enrolled 27 patients until June 2010. The median age was 58 years (range 34–87). 12 were females and 15 were males. The median number of prior therapies was 4 (range 1–20). The median follow-up period for survivors was 24 months (range 2–30 months). 14 patients were treated in the phase I part of the study and 13 patients were enrolled in phase II so far. 3 patients received 100 mg, 3 patients received 150 mg, and 8 patients received 200 mg daily. The MTD was determined to be 200 mg PO daily. This was later reduced to 150 mg PO daily when a higher incidence of grade 3 pleural effusions was noted (2 of 10 patients receiving 200 mg dose in the first stage of phase II) . 19 patients were evaluable for clinical response after 2 cycles of treatment and are as follows: CR 2, PR 4, SD 8, and PD 5. The ORR was 6/19 (32%). PFS was 17% (with a 95% CI of 5–34%) at 1 year, and 13% (3-29%) at 2 years. Overall survival was 60% (95% CI 38–76%) at 1 year and 50% (95% CI 29–68%) at 2 years. The 2 patients who sustained a CR had peripheral T-cell lymphoma (PTCL). Both patients remained alive, and disease free, for over 2 years since start of treatment. The histological subtypes of the 4 patients who had a PR were: diffuse center follicular lymphoma (2), marginal zone lymphoma (1), and peripheral T-cell lymphoma (1). NCI grade III-IV toxicities noted were hematological (5 thrombocytopenia, 2 anemia, 1 leukopenia, 3 neutropenia), pleural effusion (6), rash (1), diarrhea (2), weakness/orthostasis (1), prolonged QTc interval (1), flash pulmonary edema (1), and skin graft failure (1). In conclusion, Dasatinib shows encouraging activity in heavily pre-treated, recurrent or refractory NHL patients. Toxicity is acceptable and pleural effusions, in addition to cytopenias, were the major toxicities. Dasatinib may be particularly effective in patients with PTCL; possibly because of high expression of PDGFR-α. Phase II of the study is ongoing. Disclosures: No relevant conflicts of interest to declare.