A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.

BACKGROUND: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. PATIENTS AND METHODS: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. RESULTS: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. CONCLUSION: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. CLINICALTRIALSGOV: NCT02409472.

Angiogenic and signalling proteins correlate with sensitivity to sequential treatment in renal cell cancer.

BACKGROUND: We aimed to study key signalling proteins involved in angiogenesis and proliferation on the response to inhibitors of tyrosine kinases and mammalian target of rapamycin in first- and in second-line treatment of renal cell carcinoma (RCC). METHODS: In a panel of human RCC tumours, in vitro and in nude mice, we evaluated the effect of sunitinib, sorafenib and everolimus, alone and in sequence, on tumour growth and expression of signalling proteins involved in proliferation and resistance to treatment. RESULTS: We demonstrated that, as single agents, sunitinib, sorafenib and everolimus share similar activity in inhibiting cell proliferation, signal transduction and vascular endothelial growth factor (VEGF) secretion in different RCC models, both in vitro and in tumour xenografts. Pre-treatment with sunitinib reduced the response to subsequent sunitinib and sorafenib but not to everolimus. Inability by sunitinib to persistently inhibit HIF-1, VEGF and pMAPK anticipated treatment resistance in xenografted tumours. After first-line sunitinib, second-line treatment with everolimus was more effective than either sorafenib or rechallenge with sunitinib in interfering with signalling proteins, VEGF and interleukin-8, translating into a significant advantage in tumour growth inhibition and mice survival. CONCLUSION: We demonstrated that a panel of angiogenic and signalling proteins can correlate with the onset of resistance to sunitinib and the activity of everolimus in second line.

Typical signs of oncocytic papillary renal cell carcinoma in everyday clinical praxis.

PURPOSE: Types 1 and 2 by Delahunt of papillary renal cell carcinoma (PRCC) are traditionally differentiated. An oncocytic variant of PRCC (O-PRCC) has recently been described. We compare clinical data of O-PRCC with other subtypes of PRCC such as the main tumour size, necrotic changes, presence of pseudocapsula and real extrarenal growth in retrospective study. METHODS: From 1/1992 to 10/2009, 1,398 patients with 1,436 renal tumours were surgically treated in our institution. PRCCs were described in 109 (7.6%). Among PRCC, O-PRCCs were in 12 (11%), PRCC type 1 in 86 (78.9%), PRCC type 2 in 8 (7.3%) and others in 3 (2.8%) cases. RESULTS: The patient's mean age with O-PRCC (M:F ratio = 2:1) was 67.5 +/- 10.9 versus 63.5 +/- 14.1 in type 1 and 57.9 +/- 5.7 in type 2, the mean tumour size was 35 +/- 12 mm versus 47 +/- 22 and 37 +/- 17, respectively. The follow-up of O-PRCC is 35.3 +/- 12.3 months and all cases are without recurrence. We did not find any pseudocapsula in O-PRCC but it was a major sign of PRCC type 1 (32.6%). Huge microscopic necrotic changes were described in 33.3% of O-PRCC, in 33.7% of PRCC type 1 and 62.5% of PRCC type 2. Extrarenal growth was found only in 16.7% O-PRCC versus 40.7% in PRCC type I. CONCLUSIONS: None of the O-PRCC had pseudocapsula and none had massive necroses in comparison of O-PRCC with PRCC types I and II. Extrarenal growth in O-PRCC is relatively rare. The malignant potential of O-PRCC is low.

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas.

The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB overexpression is the result of the specific translocation t(6;11)(p21;q12), which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in 17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas. Seven cases showed a t(6;11)(p21;q12), ten cases showed translocations involving Xp11.2; five cases t(X;1)(p11;q21) resulting in a PRCC-TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF-TFE3 gene fusion, one t(X;17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one t(X;3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types.

Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer.

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.

PD-1 blockade therapy in renal cell carcinoma: current studies and future promises.

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway.

Clear cell "sugar" tumor of the pancreas. A novel member of the family of lesions characterized by the presence of perivascular epithelioid cells.

We report at unique, previously unreported pancreatic tumor occurring in a 60-year-old woman who was preoperative diagnosed on cytoaspiration as having clear cell carcinoma. The resected tumor consisted of a population of large epithelioid cells with clear or eosinophilic, granular cytoplasm, rich in glycogen, with nuclear pleomorphism and no mitotic activity. In spite of the epithelioid appearance, the tumor cells were negative for epithelial (CAM 5.2, KL1, AE1-AE3), endocrine (neuron-specific enolase [NSE], chromogranin A), and acinar (lipase, amylase) markers and positive for actin and melanogenesis-related marker HMB 45. Ultrastructurally, the neoplastic cells showed membrane-bound granules; no evidence of either epithelial or melanocytic differentiation was present. These morphophenotypic features have never been reported in a pancreatic tumor and overlap those of clear cell "sugar" tumor of the lung. The same morphophenotypic features are observed in a family of lesions characterized by the presence of the perivascular epithelioid cell that also includes lymphangiomyomatosis and angiomyolipoma. The present case may be considered a novel member of this family of lesions. We propose this new entity be named clear cell "sugar" tumor of the pancreas.

Transbronchial biopsy in lymphangiomyomatosis of the lung. HMB45 for diagnosis.

We have investigated the presence of smooth muscle cells with immunoreactivity for melanoma-related marker HMB45 in pulmonary lymphangiomyomatosis (PLAM). Of 75 lung specimens, including a variety of lesions (obtained with both transbronchial and open lung biopsies), only PLAM (six specimens from three patients) showed the presence of HMB45-positive cells. In addition, 20 specimens of normal lung were unreactive with this monoclonal antibody. It is concluded that the smooth muscle cells of PLAM regularly exhibit a peculiar phenotype, characterized by HMB45 immunoreactivity, distinct from other smooth muscle proliferations; and the histological diagnosis of PLAM can be made when only a transbronchial biopsy is available.

Apparent renal cell carcinomas in tuberous sclerosis are heterogeneous: the identification of malignant epithelioid angiomyolipoma.

Renal epithelial tumors (carcinoma and oncocytoma) have been reported with higher a frequency than expected in patients with the tuberous sclerosis complex. However, the recent identification of a monotypic, epithelioid variant of angiomyolipoma, closely simulating renal cell carcinoma, has cast doubt on the real frequency of carcinoma. Immunohistochemical analysis with a panel of antibodies, including melanogenesis marker HMB45, can discriminate between carcinoma and carcinoma-like angiomyolipoma. We studied five tumors previously reported as carcinoma and found that only one of them showed an immunohistochemical phenotype indicative of an epithelial tumor (Ker+, HMB45-). Three tumors exhibited a phenotype compatible with the monotypic epithelioid variant of angiomyolipoma (HMB45+, Ker-), and two of the three patients died of metastatic disease. The last patient had unusual clinical features, and the tumor was positive both for HMB45 and keratin. It is concluded that (1) renal cell carcinoma is less common in tuberous sclerosis complex than previously believed, (2) some cases called renal cell carcinoma probably represent a monotypic, epithelioid variant of angiomyolipoma, and (3) epithelioid angiomyolipoma is a potentially malignant tumor with invasion and metastases. These findings indicate that all reported renal carcinomas in tuberous sclerosis complex, therefore, must be reevaluated.

Neoplastic epithelial cells in a subset of human thymomas express the B cell-associated CD20 antigen.

A series of 36 human thymomas have been immunohistochemically analyzed using a panel of antibodies recognizing B-cell markers including CD20. Most thymomas exhibiting the cortical pattern, according to the criteria of Marino and Muller-Hermelink, were characterized by areas of medullary differentiation containing variable numbers of CD20+ B lymphocytes, thus mimicking the medulla of normal thymus. On the other hand, B cells were absent or rare in thymomas recognized as mixed using the same morphological criteria. Surprisingly, we observed in most mixed thymomas variable numbers of CD20+ spindle cells, characterized by long slender processes. Using double-marker analysis we could demonstrate the epithelial nature of these cells (expression of keratin and lack of lymphoid and B-cell-related markers). The immunoreactivity of thymoma epithelial cells with L26, an antibody widely used in the characterization of B-cell lymphomas, can represent a drawback of practical relevance in the differential diagnosis of mediastinal tumors.

Renal angiomyolipoma with epithelioid sarcomatous transformation and metastases: demonstration of the same genetic defects in the primary and metastatic lesions.

Angiomyolipoma (AML) is a benign neoplasm that occurs either sporadically or in patients with tuberous sclerosis complex (TSC) and shows frequent allelic losses at chromosome arm 16p. It has been suggested recently that the melanogenesis marker-positive perivascular epithelioid cell (PEC) has been found consistently in AML. The authors report a 50-year-old woman without evidence of TSC affected by classic renal AML containing an area composed of atypical epithelioid cells with the same morphoimmunophenotypic characters of PEC. After 7 years from surgical removal of the lesion, the patient developed a local recurrence and successive lung and abdominal metastases that showed morphologic and immunohistochemical features overlapping those of the epithelioid area of the previously removed AML. Genetic analysis showed that the classic AML and its epithelioid area as well as the pulmonary and abdominal metastases shared the same allelic loss on chromosome arm 16p. Based on these findings, the authors view this case as evidence of a malignant transformation of a classic AML with morphologic, immunophenotypic, and genetic demonstration of its clonal origin.

Carcinomalike monotypic epithelioid angiomyolipoma in patients without evidence of tuberous sclerosis: a clinicopathologic and genetic study.

We report the clinicopathologic, immunohistochemical, ultrastructural, and genetic features of an unusual renal tumor composed of large, atypical, densely packed, clear/eosinophilic epithelioid cells. Three patients, two men and one woman (ages 31, 36, and 60 years of age, respectively), had abdominal pain. Morphologically, all cases showed aggressive features (largeness, atypical cells, sarcomatoid features, necrosis, and, in one case, invasion of the renal vein). Despite the marked morphologic resemblance of these tumors to high-grade sarcomatoid renal cell carcinoma, their phenotype (HMB45+, CD68+/-, actin+/-, and vimentin and keratin negative) is in contrast to that observed in epithelial tumors and parallels the phenotypic profile of angiomyolipoma. Ultrastructural analysis showed the presence of glycogen, mitochondria, and prominent electron-dense, membrane-bound granules in the neoplastic cells, and the absence of melanosomes or premelanosomes. Genetic study, performed using polymerase chain reaction from paraffin sections, showed a loss of heterozygosity at the TSC2-containing region on 16p in one case, and on 3p in two cases, showing that multiple genetic alterations are taking place in these tumors. Follow-up has shown local recurrence in one case after 6 years, and the patient died 1 year later of cardiorespiratory failure. The other two patients are well after 26 and 10 months. All three patients were evaluated for signs of tuberous sclerosis, and findings were negative. We suggest that these tumors should be considered close relatives of the angiomyolipoma variants, composed purely of perivascular epithelioid cells. More cases and longer follow-up durations are needed to fully evaluate its prognostic implication.

Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.

OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors. METHODS: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed. RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.

Breast carcinoma with positive results for melanoma marker (HMB-45). HMB-45 immunoreactivity in normal and neoplastic breast.

HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity has been detected by the immunoperoxidase technique in the cytoplasm of 2 of 100 breast carcinomas. In addition, normal breast lobules and ducts were occasionally found to have positive results in 6 of 100 cases. These findings indicate the need to exercise caution in the interpretation of HMB-45 immunoreactivity for immunohistochemical characterization of neoplasms.

False-positive immunostaining of normal epithelia and carcinomas with ascites fluid preparations of antimelanoma monoclonal antibody HMB45.

HMB45 is a melanoma-specific monoclonal antibody that has found widespread use in diagnostic pathology. Recent reports, however, have suggested that this antibody may cross-react with a small number of carcinomas and other epithelial cells. The authors tested the hypothesis that these latter reports represent examples of false-positive immunostaining by comparing the immunostaining on breast, salivary gland, and lung tumors with the following: (1) a commercial ascites preparation of this monoclonal antibody; (2) a protein A-purified antibody preparation derived from ascites fluid; and (3) supernatant fluid obtained from the hybridoma cell line. The authors found that all examples of nonmelanoma immunostaining in the carcinomas tested were eliminated with the nonascites fluid preparations, whereas strong immunostaining of melanomas was retained. The authors conclude that contaminated commercial ascites fluid preparations of HMB45 may account for most, if not all, of the reports of nonmelanoma immunostaining with HMB45.

Magno- and parvocellular pathways are segregated in the human optic tract.

There is abundant psychophysical evidence in humans suggesting the existence of parallel pathways subserving different aspects of vision. However, there is little direct proof of the neural structures underlying the two pathways. We present direct anatomical evidence that in the normal human optic tract fibres are segregated according to size. Large axons, likely to correspond to the magnocellular pathway of non-human primates, take a more ventral and superficial course than the smaller axons belonging to the parvocellular pathway. This anatomical segregation not only reinforces the hypothesis of parallel pathways but, more importantly, offers a unique opportunity for studying the psychophysical effects of selective damage to one or the other fibre contingent.

Anti-melanoma monoclonal antibody HMB-45 on enhanced chemiluminescence-western blotting recognizes a 30-35 kDa melanosome-associated sialated glycoprotein.

HMB-45 is an anti-melanoma monoclonal antibody widely used in diagnostic pathology owing to its great specificity in identifying poorly differentiated melanomas. In this study, by a series of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblots with the enhanced chemiluminescent (ECL) detection method on the HU-214 melanoma cell line, we identified the antigen of HMB-45 in a protein or proteins of 30-35 kDa. Although this result is in discrepancy with the previous literature which identified the antigen as a protein of 7 or 10 kDa, a family of proteins of 25-70 kDa of as a protein of 100 kDa (gp100), the present data indicate that the antigen signal we found might be specific. Furthermore, immunoblots on neuraminidase-treated cell lysates show, in agreement with already published data, that the antigen might be a sialated glycoprotein with the sialic acid involved in the epitope. Immunoblots on partially purified melanosomes confirmed the presence of the antigen in these organelles.

Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma--the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC).

We report a comparative study of 3 clear cell tumors of the lung (CCTL) and 3 angiomyolipomas (AML) of the kidney. Morphological analysis shows that the cells of CCTL are identical to the perivascular epithelioid component of AML. Phenotypically they both consistently expressed melanoma-associated antigens recognized by Moabs HMB45 and HMSA-1, while they were negative for HMSA-5. A minority of cells also expressed S-100 protein, vimentin and actin. In addition, one case of CCTL showed mature adipose tissue entrapped in the proliferation, thus suggesting an intermediate form between CCTL and AML. Based on morphological and phenotypical similarities, it is suggested that CCTL and AML belong to the same family of lesions, characterized by the presence of a peculiar muscle cell, expressing different melanoma-associated antigens.

Preoperative diagnosis of renal angiomyolipoma: fine needle aspiration cytology and immunocytochemical characterization.

A preoperative diagnosis of renal angiomyolipoma (AML) is of great importance for a correct management of these patients with this tumor. In fact when the lesion is small and asymptomatic a conservative approach may be considered. We have evaluated the radiographic and fine needle aspiration cytology (FNAB) findings in 8 cases of AML. In 3 cases both radiology and cytology were suggestive of carcinoma and thus the patients underwent surgery. In one case both techniques suggested AML but surgery was performed because the lesion was large and symptomatic. In 4 cases where both radiology and cytology suggested AML no surgery was performed. Follow-up data are consistent with the benign nature of the lesions. The immunocytochemical analysis of the FNAB with a panel of antibodies including keratin, vimentin, actin and HMB-45 was indicative of AML in 7 of 8 cases, including 2 of the 3 cases misdiagnosed as carcinomas. The presence of HMB-45-positive perivascular epithelioid cells in the FNABs was the most significant finding. It is concluded that immunocytochemical analysis of FNAB with this monoclonal antibody panel can increase the accuracy of preoperative diagnosis of AML, and allow consideration of a conservative approach in selected cases.

Melanocyte-marker-HMB-45 is regularly expressed in angiomyolipoma of the kidney.

HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity was investigated in 10 cases of angiomyolipoma (AML) (1 with massive regional lymph node involvement) of the kidney and detected in all of them. No HMB-45 immunoreactivity was found in other tumors of the region which can occasionally be confused with AML, such as renal cell carcinoma, Wilms' tumor, and retroperitoneal sarcoma (leiomyosarcoma and liposarcoma). These findings indicate that HMB-45 is not a melanocyte-restricted marker and suggest that its expression might be useful in distinguishing AML from other tumors of the kidney and retroperitoneum.