Maria Colome

Multi-Institutional Melanoma Lymphatic Mapping Experience: The Prognostic Value of Sentinel Lymph Node Status in 612 Stage I or II Melanoma Patients

PURPOSE To compare the effect of pathologic sentinel lymph node (SLN) status with that of other known prognostic factors on recurrence and survival in patients with stage I or II cutaneous melanoma. PATIENTS AND METHODS We reviewed the records of 612 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine the effects of tumor thickness, ulceration, Clark level, location, sex, and SLN pathologic status on disease-free and disease-specific survival. RESULTS In the 580 patients in whom lymphatic mapping and SLN biopsy were successful, the SLN was positive by conventional histology in 85 patients (15%) but negative in 495 patients (85%). SLN status was the most significant prognostic factor with respect to disease-free and disease-specific survival by univariate and multiple covariate analyses. Although tumor thickness and ulceration influenced survival in SLN-negative patients, they provided no additional prognostic information in SLN-positive patients. CONCLUSION Lymphatic mapping and SLN biopsy is highly accurate in staging nodal basins at risk for regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Furthermore, pathologic status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for recurrence. The information from SLN biopsy is particularly helpful in establishing stratification criteria for future adjuvant trials.

Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma.

PURPOSE To determine the patterns of recurrence and causes of regional nodal basin failure in stage I or II melanoma patients who had a histologically negative sentinel lymph node (SLN) and whose regional nodal basins were not dissected following lymphatic mapping and SLN biopsy. PATIENTS AND METHODS The records of 344 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1995 at The University of Texas M.D. Anderson Cancer Center were reviewed. Of 322 patients who underwent successful lymphatic mapping procedures, 270 had histologically negative SLNs; mapped nodal basins were observed without further surgical intervention in 243 of these 270 patients. Recurrence patterns were analyzed from this cohort and a histologic reevaluation of all previously identified SLNs on which a biopsy had been taken was performed in patients who developed recurrent disease. RESULTS Of 243 patients with a histologically negative SLN, 27 (11%) developed local, in-transit, regional nodal, and/or distant metastases after a median follow-up time of 35 months. Ten patients (4.1%) developed a nodal recurrence in the previously mapped basin, either solely or as a component of the first site of recurrence. Detailed analysis of the SLNs in these 10 patients demonstrated evidence of occult metastases in 80% by serial sectioning or immunohistochemical staining. CONCLUSION Regional nodal failures in melanoma patients following a negative SLN biopsy are infrequent and to date have most commonly occurred because conventional histologic evaluation was unable to identify occult metastatic disease. These data provide further evidence that lymphatic mapping and SLN biopsy accurately reflect the status of the regional nodal basin. Specialized pathologic techniques are necessary to reduce further the already low false-negative rates and to improve disease staging.

Prognostic factor analysis in mycosis fungoides/Sézary syndrome

BACKGROUND The influence of prognostic factors on survival in patients with mycosis fungoides/Sézary syndrome (MF/SS) is less well described than for other lymphomas. OBJECTIVE Our purpose was to evaluate the prognostic value of diverse clinicopathologic and laboratory characteristics in patients with MF/SS. METHODS All 115 patients with MF/SS seen at the Mycosis Fungoides clinic at M. D. Anderson Cancer Center during the study period who had slides available for pathologic review were analyzed. Univariate and multivariate methodologies were used. RESULTS Age (> or = 60 years; P = .0002), advanced stage (P < 10(-5)), tumor (T3) stage disease (P < or = 10(-5)), lymphadenopathy (P = .006), bone marrow infiltration (P = .03), high lactate dehydrogenase (LDH; P = .0002), high beta2-microglobulin (> 2 mg/L; P = .009), and transformation to large-cell lymphoma (P = .004) were significant prognostic factors in the univariate analysis and correlated with a poorer survival. The outcome of patients staged as IIB was significantly worse than that of those staged as I or IIA or III (P < .001) and was comparable to that of the patients staged as IV (P = .8). In the multivariate analysis, the factors selected include stage (I to IIA and III vs IIB and IV; P < .0001), LDH (P = .006), and age (> or = 60 vs < 60 years; P = .02). The actuarial median survival of patients with advanced stage, high LDH, or age 60 years or more was 2.5 to 3.5 years, whereas that of patients without any of these parameters was more than 13 years. CONCLUSION Our results suggest that patients with MF/SS who are staged as IIB or IV, who have a high LDH, or who are 60 years of age or older have an aggressive course and poor survival.

Pagetoid bowen disease: a report of 2 cases that express cytokeratin 7.

Bowen disease is a variant of squamous cell carcinoma in situ. In some cases a pagetoid growth pattern can be observed with cytologically atypical clear cells arranged singly and in nests. The differential diagnosis of pagetoid Bowen disease includes primarily Paget disease and malignant melanoma in situ, as well as other less common entities. Two cases of pagetoid Bowen disease are described, one in a 65-year-old man with a thigh lesion and the other in a 25-year-old man with a lesion in the penile/scrotal region. Neither patient had clinical evidence of an internal malignant neoplasm. In both cases, the neoplastic cells were positive for cytokeratin (CK) 7 and CK 19 and were negative for CK 18, CK 20, carcinoembryonic antigen, GCDFP-15, c-erbB2, S100, and HMB-45. In aggregate, these findings support the diagnosis of pagetoid Bowen disease. Previously, others have shown that CK 7 is an almost invariable marker of Paget disease. Thus, we report these two cases to illustrate that CK 7 can be expressed by pagetoid Bowen disease and should not be a cause of confusion in the differential diagnosis.

Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases

Our results with concurrent biochemotherapy in patients with stage IV melanoma have been encouraging. Based on these data, we conducted a phase II study to determine the clinical and histological response rate to neoadjuvant concurrent biochemotherapy in patients with local-regional metastases of cutaneous melanoma (stage III). A total of 65 patients with biopsy-proven, measurable and potentially resectable local-regional disease (nodal, satellite/in-transit metastases and/or local recurrence) were treated with cisplatin 20 mg/m2 intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4, dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by 96 h continuous infusion on days 1 to 4, and interferon-cc2a 5 MU/m2 subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery after two to four courses of biochemotherapy. Those with tumour regression after two preoperative courses received two additional postoperative courses. Of the 64 patients assessable for clinical response, 28 (44%) had a partial response. Of the 62 patients whose response was assessed histologically, four (6.5%) had no evidence of viable tumour in the surgical specimen (pathological complete remission, pCR) and 27 (43.5%) had a partial response, giving an overall response rate of 50%. Tumour burden did not correlate with response, although patients who achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II study indicates that neoadjuvant biochemotherapy is an active treatment for melanoma patients with local-regional metastases. However, it is unclear if biochemotherapy is more active than chemotherapy alone; phase III randomized trials are ongoing to answer this question in patients with stage IV disease. 1998 Lippincott Williams & Wilkins

Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.

PURPOSE To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation. PATIENTS AND METHODS Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group). RESULTS All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant. CONCLUSION Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

Hyaluronic acid filler for steroid atrophy.

The use of hyaluronic acid for atrophy has not been documented in the literature. In this manuscript we present a case of a patient treated with the aforementioned filler with enthusiastic results. This case shows yet another potential application for these novel products.

Research Letter: Hyaluronic acid filler for steroid atrophy

The use of hyaluronic acid for atrophy has not been documented in the literature. In this manuscript we present a case of a patient treated with the aforementioned filler with enthusiastic results. This case shows yet another potential application for these novel products.

Verrucous cyst with melanocytic and sebaceous differentiation: a case report and review of the literature.

A 58-year-old woman presented with a cystic skin lesion. Microscopic examination showed an intradermal cyst lined by acanthotic squamous epithelium with squamous eddies and compact hyperkeratosis, and changes typical of verrucous lesions. Mature sebaceous cells and dendritic melanocytes were present as well. To our knowledge, this is the first report of a verrucous cyst with areas of sebaceous differentiation and melanocytes. Verrucous cysts are well-known, benign lesions with a clear histologic pattern. Histologically, they resemble verruca vulgaris with acanthosis, hypergranulosis, dense keratohyaline granules, and viral cytopathic effects seen. Until now, melanocytes and mature sebaceous cells in the cyst lining have not been reported. We do not feel that these findings alter the expected benign nature of this lesion. Instead, we report this case to suggest the possible adnexal embryonic origin, given the presence of sebaceous cells and dendritic melanocytes that support this histologic lineage in our specific case.

Research Letter: Hyaluronic acid filler for steroid atrophy: Hyaluronic acid filler

The use of hyaluronic acid for atrophy has not been documented in the literature. In this manuscript we present a case of a patient treated with the aforementioned filler with enthusiastic results. This case shows yet another potential application for these novel products.