GLUT1 immunoreaction patterns reliably distinguish hemangioblastoma from metastatic renal cell carcinoma

BACKGROUND: Hemangioblastoma and metastatic renal cell carcinoma (RCC) may show striking histologic similarities, and the distinction between these two tumors can be difficult. Both occur in middle age, and both occur with increased incidence in von Hippel-Lindau disease (vHL). GLUT1 is an erythrocyte-type glucose transporter protein that is highly expressed by endothelia in brain--but not most peripheral--microvasculature, and by tumor cells in many epithelial malignancies. GLUT1 is expressed by endothelial cells in juvenile hemangiomas, and endothelial GLUT1 expression has been reported for 2 hemangioblastomas arising in a single patient with vHL. METHODS: We performed immunoreactions for GLUT1 on archival hemangioblastomas from 12 patients (one with vHL), and on RCCs metastatic to brain of 9 patients. RESULTS: Hemangioblastomas showed intense endothelial GLUT1 reactivity in 11/12 tumors resections; the only GLUT1-negative tumor was one for which only previously frozen material was available for immunoreaction, and this tissue showed poor GLUT1 immunoreactivity of internal erythrocyte controls. Hemangioblastoma stromal cell reactivity was found in only 1 case, and was weak and focal. RCCs, in contrast, showed no intralesional endothelial GLUT1 reactivity, but did show intense tumor cell membrane reactivity in 9/9 cases. CONCLUSION: that GLUT1 immunoreactivity patterns reliably distinguish hemangioblastoma from RCC.     

HIV infection in haemophilia--a European cohort

Ten haemophilia centres in northern Europe have pooled data on 202 haemophilic children who were infected with HIV between 1979 and 1986. All cases were under 16 years of age on 1 July 1985. The age at infection ranged from 1-15 years. Thirty seven cases (18%) had progressed to AIDS by 1 July 1991 and 15 of these have died. Persistent generalised lymphadenopathy has been noted in 102 patients of whom 18 (17%) have developed AIDS. Twenty three of the remaining patients (23%) have not. CD4+ T cell counts have fallen steadily. Of 36 patients who have had shingles since seroconversion, 19 (53%) had counts below 0.2 x 10(9)/l. Thirty five out of 145 patients without shingles (24%) had similar values. The mean IgA concentration in patients with CD4+ T cell counts above 0.5 x 10(9)/l was 2.38 g/l, between 0.2 and 0.5 was 3.07 g/l, and in those with CD4+ T cell counts below 0.2 x 10(9)/l the mean IgA concentration was 4.58 g/l. Treatment patterns have altered between 1989 and 1991, with increased use of zidovudine in patients without AIDS and a marked increase in primary prophylaxis against pneumocystis pneumonia. This has been associated with a decline in the incidence of pneumocystis as an indicator disease in new AIDS cases from 56% in 1989 to 20% in 1991. These observations indicate that persistent generalised lymphadenopathy does not worsen the outlook, but shingles does. Rising IgA concentrations are markers for disease progression. Modern prophylactic regimens are delaying the onset of indicator disease, but CD4 values continue to fall steadily.     

Molecular diagnostics in melanoma

Molecular pathology is rapidly evolving, featuring continuous technologic improvements that offer novel clinical opportunities for the recognition of disease predisposition, for identifying sub-clinical disease, for more accurate diagnosis, for selecting efficacious and non-toxic therapy, and for monitoring of disease outcome. Currently, the identification and prognosis of primary cutaneous melanoma is based on histologic factors (tumor depth and ulceration) and clinical factors (number of lymph node and/or distant metastases). However, metastasis can occur in patients with thin melanomas, and sentinel lymph node biopsy does not identify all patients at risk for distant metastasis. New markers exist that correlate with melanoma progression, which may aid in melanoma identification, prognostication, and detection of minimal residual disease/early recurrence. Moreover, not many therapeutic options exist for melanoma as no regimen prolongs survival. Emerging data with investigational therapies suggest that certain markers might play a crucial role in identifying patients who will respond to therapy or show utility in the monitoring the response to therapy. Herein, molecular diagnostics that can potentially benefit the individual melanoma patient will be discussed.     

Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary?

HYPOTHESIS: Completion lymph node dissection (CLND) has usually been recommended after metastatic disease is identified in the sentinel lymph node (SLN) biopsy to eradicate further metastases in nonsentinel nodes. We hypothesized that patients with negative lymph nodes included in the initial SLN specimen have low risk of metastases in the residual draining basin and may not require CLND. DESIGN: Chart review. SETTING: University-affiliated tertiary care referral center. PATIENTS: Between January 1, 1997, and May 31, 2003, 506 consecutive patients underwent SLN biopsy for staging of primary cutaneous melanoma. INTERVENTION: The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 underwent CLND. RESULTS: In 28 patients, all SLNs were found to contain metastatic melanoma. Seven (25%) of these patients had additional metastases identified in the CLND specimen. In 52 patients, 1 or more SLNs did not contain metastatic melanoma. Five (10%) of these patients had additional metastases in the CLND specimen (P =.02). CONCLUSIONS: Although no evidence of metastatic melanoma was found on CLND in most patients in whom negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further metastases. This subgroup of patients (positive SLNs and negative nodes in the SLN biopsy specimen) is at significantly lower risk for further metastasis, but CLND cannot be safely omitted even for these patients.     

An evidence-based staging system for cutaneous melanoma

A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.     

Pathology of malignant melanoma

Understanding the fundamental aspects of the pathology of melanoma is crucial for the surgeon to deliver optimal care to the patient with melanoma. Pathology provides diagnostic data, offers prognostic information, and, to a large extent, directs management. This article reviews several aspects of the pathology of melanoma, with special relevance to the surgeon, including benign clinicopathologic simulators of melanoma, fundamental concepts of the pathology of melanoma, histopathologic prognostic factors of melanoma, approach to lymph nodes, and implications of the revised staging system.     

New TNM melanoma staging system: linking biology and natural history to clinical outcomes

The American Joint Committee on Cancer (AJCC) implemented major revisions of the melanoma TNM and stage grouping criteria in the recently published 6th edition of the Staging Manual. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include: 1) melanoma thickness and ulceration but not level of invasion to be used in the T classification, 2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of microscopic vs. macroscopic nodal metastases to be used in the N classification, 3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M classification, 4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated, 5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease, and 6) a new convention for defining clinical and pathological staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.