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ABSTRACT: In the American Joint Committee on Cancer (AJCC)-TNM (2009) staging system, the key prognostic factor in cutaneous melanoma is the depth of dermal invasion (Breslow thickness) with further refinement according to the presence of epidermal ulceration or dermal mitoses. Immunodetection of phosphohistone H3 has been shown to facilitate the identification of mitotic figures in various neoplasms. We selected 120 cases of primary cutaneous melanoma with completely annotated histopathologic parameters and clinical outcomes and performed double immunohistochemical staining for MLANA (Mart-1/Melan-A) and phosphohistone H3. One hundred and thirteen cases were amenable to antiphosphohistone H3 staining from 66 men and 47 women, with mean age of 64 years (9-93), including 61 superficial spreading type, 24 nodular, 6 lentigo maligna, 8 acral lentiginous, and 14 unclassified. The mean Breslow thickness was 2.53 mm (0.20-25), ulceration was present in 25/113 (22%) and the mean mitotic count was 3.2/mm(2) (<1-29/mm(2)). In 27/113 (24%) of the cases, antiphosphohistone H3 failed to highlight mitotic figures anywhere in the tissue (normal or tumor cell), whereas in 86/113 (76%) antiphosphohistone H3 detected at least one mitotic figure. Among the latter, antiphosphohistone H3 did not detect mitotic figures in dermal tumor cells in 37/86 cases (43%), whereas anti-PHH3 identified at least one melanocytic mitotic figure in the other 49/86 cases (57%; range: 1-66/mm(2)). The relationship between phosphohistone H3 and manual mitotic count was statistically significant (Pearson correlation=0.59, P<0.0001). Logistic regression analyses demonstrated an association between the development of subsequent metastatic disease and the following variables: mitotic figures (odds ratio (OR)=5.7; P=0.0001); phosphohistone H3-positive mitotic figures (OR=3.0; P=0.008); Breslow thickness (OR=4.0 per mm; P=0.0002); ulceration (OR=3.94; P=0.008). The application of phosphohistone H3 immunohistochemistry to the description of primary cutaneous melanoma is useful in identifying mitotic figures, improves upon the specificity of this designation when used together with MLANA, and correlates with an increased risk for metastasis in univariate analyses.Modern Pathology advance online publication, 5 April 2013; doi:10.1038/modpathol.2013.59.
Modern Pathology 04/2013; · 4.79 Impact Factor
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ABSTRACT: Aggressive digital papillary adenocarcinoma is a rare tumor predominantly involving the distal end of digits. We examined 31 cases of this distinctive tumor for clinicopathologic, immunohistochemical, and follow-up data where available. Males were predominantly affected (n=29), with a mean age of 43 years (range, 14 to 67 y). Three lesions were reported in patients below the age of 20 years. All cases involved a finger (n=26) or a toe (n=5), with most involving the distal portion of the digit (n=29). Two lesions involved the base of the digit/webspace. Histopathologically, all tumors involved the dermis with subcutaneous extension in 14 cases. The lesions demonstrated a multinodular solid and/or cystic pattern, with focally infiltrative architecture in 21 cases. Papillary projections were: prominent (n=10), focal (n=15), or not identified (n=6). Within the solid component, tubular structures were present at least focally in all cases. Cytologic atypia ranged from mild (n=8) to moderate (n=20), but was focally severe in 3 cases. Mitotic count ranged from <1 to 18 per mm. Focal necrosis was seen in 6 cases. Immunohistochemically stained sections were available for review in 8 cases. Tumor cells were diffusely positive for MNF116 (3 of 3). Carcinoembryonic antigen and epithelial membrane antigen highlighted the luminal border of tubules (8 of 8). Smooth muscle actin (5 of 6) and calponin (6 of 6) highlighted a myoepithelial layer around tubular/glandular structures, as did p63 (2 of 2) and podoplanin (5 of 5). Follow-up after excision or amputation (n=23; range, 2 mo- to 21 y) revealed local recurrence (n=5) and metastatic disease (n=6; lymph node in 1, lungs in 4, and both lymph node and lung in 1). Metastases were noted at presentation in 2 cases (lymph node in 1 and lung in 1), but presented as late as 14 and 20 years in lymph node and lung, respectively. Only 1 patient died of metastatic disease 6 years after initial diagnosis, after multiple recurrences and lung metastases. Three patients were alive with progressive disease up to 24 months after developing lung metastases. Histopathologic features were not found to be predictive of outcome. The presence of tumor-associated myoepithelial cells histologically and immunohistochemically was not synonymous with benignity. Wide excision and partial digit amputation significantly reduced recurrence and metastatic rates. Delayed occurrence of metastases and a protracted course despite metastatic disease, necessitates long-term follow-up. As the name implies a malignant neoplasm, the rubric "aggressive" is unnecessary.
The American journal of surgical pathology 09/2012; · 4.06 Impact Factor
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ABSTRACT: Interferon-α has been associated with a wide range of adverse events (AEs). A lupus-like reaction at the injection site of subcutaneous (SC) interferon-α is exceptionally rare. A 60-year-old woman with recurrent metastatic melanoma repeatedly developed cutaneous lupus-like reactions at the SC interferon-α-2b injection sites on her thighs. Known features of lupus-like reactions at SC interferon-α injection sites are reviewed, and cutaneous injection site reactions to SC interferon-α are summarized.
Journal of drugs in dermatology: JDD 03/2012; 11(3):393-8. · 1.57 Impact Factor
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ABSTRACT: To determine whether T category of the American Joint Committee on Cancer (AJCC) TNM staging system for eyelid carcinoma, 7th edition, correlates with lymph node metastasis, distant metastasis, and survival in patients with sebaceous carcinoma of the eyelid.
Retrospective, cohort study.
Fifty consecutive patients treated by 1 author (BE) for eyelid sebaceous carcinoma between May 1999 and August 2010.
Each tumor was staged according to the AJCC 7th edition TNM criteria. The Kaplan-Meier method was used to determine associations between disease-specific survival and (1) T category at presentation, (2) lymph node metastasis, and (3) distant metastasis.
T category at presentation, nodal metastasis, survival.
The study included 37 women and 13 men (median age, 68.5 years; range, 44-86 years). Forty-four patients were white, 5 were Hispanic, and 1 was Asian. TNM designations were TXN0M0, 7 patients; T1N0M0, 4 patients; T2aN0M0, 12 patients; T2bN0M0, 11 patients; T2bN1M0, 2 patients; T2bN1M1, 1 patient; T3aN0M0, 2 patients; T3aN1M0, 5 patients; T3bN0M0, 1 patient; T3bN1M0, 1 patient; T3bN0M1, 2 patients; T4N0M0, 1 patient; and T4N0M1, 1 patient. T category at presentation was significantly associated with lymph node metastasis (P = 0.0079). No tumors with T category better than T2b or smaller than 9 mm in greatest dimension were associated with nodal metastasis. Five patients (10%) died of disease during follow-up. Their TNM designations were T2bN1M1, 1 patient; T3bN0M1, 2 patients; T4N0M0, 1 patient; and T4N0M1, 1 patient. No tumors smaller than 12 mm in greatest dimension were associated with distant metastasis or death. T category was significantly associated with disease-specific survival (P = 0.0009). Disease-specific survival was poorer among patients with T category of T3a or worse (P = 0.035).
T category in the 7th edition of the AJCC TNM staging system for eyelid carcinoma correlates with outcomes in patients with sebaceous carcinoma of eyelid. On the basis of the present findings, it seems reasonable to recommend sentinel lymph node biopsy or at least strict regional lymph node surveillance for patients with eyelid sebaceous carcinoma with tumors of T category T2b or worse or 10 mm or more in greatest dimension.
Ophthalmology 02/2012; 119(5):1078-82. · 5.45 Impact Factor
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ABSTRACT: Rosai-Dorfman disease (RDD) is characterized histologically by a dense histiocytic infiltrate with emperipolesis and associated lymphocytes, plasma cells, and neutrophils. Eosinophils are not commonly associated. We report a patient with initial thymus and pituitary gland involvement by RDD, who later developed papules on the groin and axilla. Skin biopsies showed admixed histiocytic infiltrates (lymphocytes, neutrophils, and plasma cells) without emperipolesis. A prominent eosinophilic infiltrate was also observed, a feature not, to our knowledge, previously reported. Immunohistochemistry revealed positivity for CD68 (most cells) and S100 protein (scattered cells) and was negative for anti-CD1a. The diagnosis of RDD was established in the clinical context after comparison with the thymic and pituitary lesions (similar histologic features, albeit with fewer eosinophils, and immunohistochemical profiles). We present the first case, to our knowledge, of multicentric RDD with cutaneous involvement and associated prominent eosinophilic infiltrate. Thus, RDD should be included in the differential diagnosis of mononuclear infiltrates containing eosinophils.
Archives of pathology & laboratory medicine 12/2011; 135(12):1597-600. · 2.58 Impact Factor
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ABSTRACT: Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen.
Journal of Cutaneous Pathology 11/2011; 39(2):294-7. · 1.56 Impact Factor
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Archives of dermatology 11/2011; 147(11):1342-3. · 4.76 Impact Factor
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ABSTRACT: To evaluate the feasibility of staging eyelid carcinomas using the American Joint Committee on Cancer (AJCC) criteria, and to compare the 6(th) and 7(th) editions.
The records of 27 consecutive patients who underwent excision of eyelid carcinoma between April 2007 and April 2008 were reviewed. Patients with melanoma, lymphoid tumors, nonmeasurable disease, or medial or lateral canthal tumors were excluded. Each patient was staged using the AJCC 6(th) and 7(th) edition criteria based on clinical, pathologic, and radiographic data.
The study included 13 men and 14 women aged 32 to 93 years (median, 65 years). Seventeen patients had basal cell carcinoma; 3, squamous cell carcinoma; 6, sebaceous carcinoma; and 1, Merkel cell carcinoma. Tumor location was lower eyelid in 20 patients and upper eyelid in 7. TNM designations were reliably determined for all 27 patients and were: A) using the 6(th) edition: T1N0M0, 6 patients; T2N0M0, 6; T2N1M0, 1; T3N0M0, 4; T4N0M0, 9; and T4N1M0, 1. B) using the 7(th) edition: T1N0M0, 6 patients; T2aN0M0, 8; T2aN1M0, 1; T2bN0M0, 2; T3aN0M0, 6; T3aN1M0, 1; T3bN0M0, 2; and T4N0M0, 1. Pathologic tumor size and nodal status, and systemic work-up were recorded for all patients.
Eyelid carcinomas can be reliably staged using the AJCC criteria. There are notable differences between the 6(th) and 7(th) editions of AJCC TNM designation. We recommend AJCC staging using the latest published edition during the initial work-up for all patients with eyelid carcinoma to make reporting of outcomes more reliable and reproducible.
Orbit (Amsterdam, Netherlands) 10/2011; 30(5):202-7.
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ABSTRACT: Accurate diagnosis of melanocytic lesions is essential for the adequate clinical management of patients. Thus, thorough reporting of histopathologic parameters, especially in the initial biopsies, is a critical component of both diagnosis and staging.
To review current data on histopathologic prognostic factors for melanoma, with special emphasis on their use and applicability to clinical practice. Special attention is focused on the criteria highlighted by the new 2009 version of The American Joint Committee on Cancer (AJCC) system of melanoma staging and classification.
Published peer-reviewed literature and personal experience of the authors.
When reporting melanoma, we recommend that a template be provided, including all the histologic parameters that have been proved significant in determining the tumor staging and prognosis of a patient. The template may also include other details that may be helpful in further analysis of potential complete excisional biopsies or metastatic lesions, such as predominant type of tumor cells, presence or absence of desmoplastic component, or associated benign melanocytic lesions. Although there are several drawbacks in reporting some of these histopathologic parameters (interobserver variability, occasional lack of a perfectly reproducible method for quantifying these criteria), we suggest that at least the essential histopathologic parameters highlighted by the newest version of the AJCC system for melanoma staging and classification should be included in the report.
Archives of pathology & laboratory medicine 07/2011; 135(7):825-9. · 2.58 Impact Factor
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ABSTRACT: Extramammary Paget's disease is a rare intra-epithelial malignancy that is occasionally associated with an invasive adenocarcinoma component as well as other secondary cancers. We investigated a consecutive series of patients referred for extramammary Paget's disease of the penis or scrotum at a single center in the contemporary era to determine the presence of secondary cancers and treatment outcomes.
Between December 1990 and February 2009, 20 patients with extramammary Paget's disease of the scrotum and/or penis were seen. Patients were investigated with computerized tomography of the abdomen/pelvis, chest x-ray, cystoscopy, colonoscopy and serum prostate specific antigen measurement to rule out obvious secondary cancer. Clinical charts were reviewed with institutional review board approval. Mean followup of treated cases was 48 months (range 7 to 208).
Patients were 50 to 86 years old with a history of symptoms of between 6 months and 10 years. Eight patients had invasive adenocarcinoma, of whom 2 died of the disease and 3 who had disease at 5, 7 and 40 months, respectively, were undergoing multimodal therapy. No patient with confirmed intra-epidermal disease only died of the disease. Invasive disease predicted nodal and metastatic progression.
Surgical resection to achieve tumor-free margins resulted in durable relapse-free survival of patients with intra-epidermal extramammary Paget's disease alone. Extramammary Paget's disease with invasion was associated with regional metastatic progression. The latter scenario as well as failure to treat localized extramammary Paget's disease alone was associated with a fatal outcome. Systemic chemotherapy should be further explored in patients with invasive adenocarcinoma or lymph node positive disease.
The Journal of urology 07/2011; 186(1):97-102. · 4.02 Impact Factor
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ABSTRACT: To report the occurrence and management of perineural invasion in patients with sebaceous carcinoma of the eyelid.
An ophthalmology database was searched for all patients treated for sebaceous carcinoma of the eyelid by the principal investigator between May 1999 and May 2010. The clinical records and pathology specimens of the patients with microscopic perineural invasion as an incidental finding in their eyelid surgical specimen were reviewed.
Forty-two patients with sebaceous carcinoma of the eyelid were treated by the principal investigator during the study period. Three of them had evidence of microscopic perineural invasion in the surgical specimen. Each patient was treated with surgery with or without radiotherapy. The first patient underwent orbital exenteration and negative sentinel lymph node biopsy, subsequently developed distant metastasis, and died 20 months after exenteration. The second patient underwent resection of the tumor and positive sentinel lymph node biopsy, postoperative irradiation of the eyelid, completion neck dissection and parotidectomy for the positive sentinel lymph node, and irradiation of nodal basins; she was free of disease at last follow up (12 months after tumor resection). The third patient underwent resection of the tumor, developed regional lymph node metastasis 3 months later, underwent lymph node dissection and postoperative nodal irradiation, and was free of disease at last follow up (9 months after tumor resection).
Perineural invasion was encountered in 7% of patients with eyelid sebaceous carcinoma. The authors' preference is to treat patients with an incidental finding of microscopic perineural invasion with postoperative adjuvant radiotherapy, ideally within 4 to 6 weeks after surgical resection of the primary eyelid tumor.
Ophthalmic plastic and reconstructive surgery 05/2011; 27(5):356-9. · 0.69 Impact Factor
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ABSTRACT: Sebaceous carcinoma is a rare cutaneous malignancy that is most frequently found in the eyelids with an estimated risk of regional lymph node metastasis in the 8% to 14% range. The authors have previously reported the use of sentinel lymph node biopsy and microscopically positive sentinel lymph nodes in various eyelid and conjunctival cancers, including conjunctival and eyelid melanoma and Merkel cell carcinoma. The authors herein describe the first successful identification of a microscopically positive sentinel lymph node in a patient with sebaceous carcinoma of the eyelid, suggesting that sentinel lymph node biopsy for sebaceous carcinoma of the eyelid deserves further investigation.
Ophthalmic plastic and reconstructive surgery 10/2010; 27(1):e4-6. · 0.69 Impact Factor
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ABSTRACT: The accurate diagnosis of melanocytic lesions is essential for the adequate clinical management of the patients. Besides the histopathologic examination, immunohistochemical studies are often used as an adjunct in distinguishing melanocytic lesions from tumors with different origin or between benign and malignant melanocytic lesions. In the first part of this article, we analyze data on currently used immunohistochemical markers, with special emphasis on their applicability to clinical practice, and underline their potential pitfalls. The pathogenesis of malignant transformation of melanocytes is not completely understood. Recent studies report that various melanoma progression markers are preferentially expressed in benign or malignant melanocytic lesions or show different expression in subsequent stages of tumor development. Furthermore, in recent years, emerging genetic studies suggest that there are distinctive patterns of chromosomal aberrations in different subtypes of melanoma that can be altered by newly developed targeted therapies. In the second part of our article, we will discuss the most significant progression markers in melanoma that can be detected by immunohistochemistry and their potential usefulness for diagnosis, prognosis, staging or as therapeutic targets.
Future Oncology 07/2010; 6(7):1163-75. · 3.16 Impact Factor
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ABSTRACT: Adipophilin is a monoclonal antibody against a protein on the surface of intracellular lipid droplets, and it was recently shown to be expressed in sebocytes and sebaceous lesions. This study examines adipophilin expression in various sebaceous lesions and other cutaneous tumors with a clear cell histology that may mimic sebaceous differentiation. A total of 117 cutaneous clear cell lesions including 16 sebaceous adenomas, 25 sebaceous carcinomas, 8 basal cell carcinomas, 12 squamous cell carcinomas, 6 xanthomas, 10 xanthelasmas, 10 xanthogranulomas, 4 balloon cell nevi, 5 trichilemmomas, 8 clear cell hidradenomas, and 13 metastatic renal cell carcinomas were examined using immunohistochemistry for the expression of adipophilin. Of these 117 lesions, 42 (36%) were from the periocular region. Adipophilin was expressed in 16 of 16 (100%) sebaceous adenomas, 23 of 25 (92%) sebaceous carcinomas, 10 of 10 (100%) xanthelasmas, 9 of 10 (90%) xanthogranulomas, 6 of 6 (100%) xanthomas, and 9 of 13 (62.5%) metastatic renal cell carcinomas. The characteristic staining pattern differed between sebaceous and non-sebaceous tumors with the former showing a membranous vesicular pattern and the latter being more granular. Adipophilin expression was not seen in any of the other lesions with clear cell histology, basal cell carcinomas, or squamous cell carcinomas, including cases that had focal clear cell differentiation. Adipophilin can be valuable in an immunohistochemical panel when evaluating cutaneous lesions with clear cell histology as it identifies intracytoplasmic lipid vesicles in sebaceous and xanthomatous lesions. In periocular lesions, it is effective in helping to exclude basal cell carcinoma and squamous cell carcinoma when sebaceous carcinoma is under consideration. Adipophilin expression is not as useful for the differential diagnosis that includes metastatic renal cell carcinoma, a rare but important, diagnostic differential. The pattern of adipophilin reactivity is important to observe as membranous vesicular staining is suggestive of intracellular lipids whereas granular cytoplasmic reactivity is not.
Modern Pathology 04/2010; 23(4):567-73. · 4.79 Impact Factor
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ABSTRACT: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin.
Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin.
Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out.
Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patient's quality of life.
Ophthalmic plastic and reconstructive surgery 02/2010; 26(2):88-94. · 0.69 Impact Factor
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ABSTRACT: Melanoma is an uncommon tumour in childhood. Only isolated cases in pregnant patients younger than 18 years old have been previously described, therefore the biological behaviour of cutaneous melanoma in this group of age remains largely unknown. We report a single-institution experience with three patients who developed cutaneous melanoma before the age of 18 years and became pregnant concomitantly or during the course of the disease. High tumour thickness was attributed to later diagnosis and could be responsible for the aggressive biological behaviour in these patients. This delay was in part due to patients considering changes in nevi to be normal during pregnancy. The effect of pregnancy on the prognosis of patients with melanoma, particularly the role of hormonal and immunological factors on clinical outcome, survival and risk of developing metastases, as well as the differences between adolescent and adult populations are still controversial. Since there are no specific treatment strategies for this group of patients, treatment recommendations should be established according to adult experience.
European journal of dermatology: EJD 02/2010; 20(2):186-8. · 2.53 Impact Factor
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Journal of Cutaneous Pathology 12/2009; · 1.56 Impact Factor
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ABSTRACT: Indeterminate fibrohistiocytic lesions of the skin share histological and immunohistochemical features of both benign fibrous histiocytoma/dermatofibroma and dermatofibrosarcoma protuberans (DFSP). Unlike dermatofibroma, DFSP harbors recurrent genetic aberrations resulting in the fusion of COL1A1 on chromosome 17 and PDGFB on chromosome 22. Because indeterminate fibrohistiocytic lesions share some features with DFSP, they were evaluated for the possible presence of COL1A1-PDGFB chimeric transcripts. Twelve formalin-fixed paraffin-embedded cases were examined for COL1A1-PDGFB chimeric transcripts using a previously validated sensitive multiplex reverse transcriptase-polymerase chain reaction assay. The median patient age was 52.5 years (33-70 years) with 9 females and 3 males. The most common site was the extremities (n = 8) followed by the trunk (n = 2) and the head and neck region (n = 2). All demonstrated the expected reactivity for both CD34 and factor XIIIa, and the majority focally infiltrated into subcutaneous fat. Of the 6 patients with follow-up, 2 had residual tumor excised, but no patient developed a recurrence. None of the tumors harbored COL1A1-PDGFB fusion transcripts identified by reverse transcriptase-polymerase chain reaction. Although indeterminate fibrohistiocytic lesions share some features with DFSP, the lack of COL1A1-PDGFB chimeric transcripts suggests that they are distinct entities.
The American Journal of dermatopathology 11/2009; 32(2):149-53. · 1.30 Impact Factor
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ABSTRACT: To report the findings on sentinel lymph node biopsy (SLNB) in 30 patients with ocular adnexal (conjunctival or eyelid) melanomas.
Prospective nonrandomized clinical trial.
Thirty patients with diagnosis of eyelid or conjunctival melanoma.
All patients with ocular adnexal melanoma who underwent SLNB at The University of Texas MD Anderson Cancer Center between December 2000 and July 2008 are the subject of this report. Sentinel lymph node biopsy was performed as previously described by our group, and patients were prospectively followed up.
Findings on preoperative lymphoscintigraphy, SLNB, histopathologic examination of the primary tumor and sentinel lymph nodes (SNL), and nodal recurrence after SLNB.
Tumor sites were as follows: bulbar conjunctiva only, 14 patients; palpebral conjunctiva only, 8 patients; both bulbar and palpebral conjunctiva, 4 patients; and eyelid skin only, 4 patients. At least 1 SLN was identified in all patients. The median number of SLNs removed was 2 (range, 1-5). The most common basin sampled was the intraparotid (16 patients), followed by submandibular (level I) (11 patients), preauricular (9 patients), and superior cervical (level II) (6 patients). Five patients had SLN metastasis. Among the 25 patients with negative SLNB findings, there were 2 false-negative events. There were no false-negative events among patients treated during the last 4.5 years of the study. The mean Breslow thickness was 2.57 mm (range, 0.62-12 mm) among patients with negative SLNB and 4.86 mm (range, 2.0-7.2 mm) among patients with positive SLNB findings (P = 0.055). Ulceration was present in 11 patients (39%): 4 (80%) of 5 patients with positive SLNB and 7 (28%) of 25 with negative SLNB, including both patients with false-negative results. The median time from SLNB to last contact was 2 years (range, 10 months to 6 years).
Sentinel lymph node biopsy is effective for identifying nodal micrometastasis in patients with ocular adnexal melanoma and provides important prognostic information. The false-negative event rate in our series improved in the last 4 years, most likely because of a better technique and better patient selection for SLNB. We recommend consideration of SLNB for patients with intermediate-thickness ocular adnexal melanoma and those with ulceration.
Ophthalmology 09/2009; 116(11):2217-23. · 5.45 Impact Factor
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Scott E Woodman,
Jonathan C Trent,
Katherine Stemke-Hale,
Alexander J Lazar,
Sabrina Pricl,
Giovanni M Pavan,
Maurizio Fermeglia,
Y N Vashisht Gopal,
Dan Yang,
Donald A Podoloff, Doina Ivan,
Kevin B Kim,
Nicholas Papadopoulos,
Patrick Hwu,
Gordon B Mills,
Michael A Davies
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ABSTRACT: Point mutations in the KIT receptor tyrosine kinase gene have recently been identified in mucosal, acral lentiginous, and chronically sun-damaged melanomas. We have identified the first human melanoma cell line with an endogenous L576P mutation, the most common KIT mutation in melanoma ( approximately 30-40%). In vitro testing showed that the cell viability of the L576P mutant cell line was not reduced by imatinib, nilotinib, or sorafenib small molecule KIT inhibitors effective in nonmelanoma cells with other KIT mutations. However, the viability of the mutant cells was reduced by dasatinib at concentrations as low as 10 nM (P = 0.004). Molecular modeling studies found that the L576P mutation induces structural changes in KIT that reduce the affinity for imatinib (DeltaDeltaGbind = -2.52 kcal/mol) but not for dasatinib (DeltaDeltaGbind = +0.32 kcal/mol). Two metastatic melanoma patients with the L576P KIT mutation were treated with dasatinib, including one patient previously treated with imatinib. Both patients had marked reduction (>50%) and elimination of tumor F18-fluorodeoxyglucose (FDG)-avidity by positron emission tomography (PET) imaging after dasatinib treatment. These data support the selective inhibitory effect of dasatinib against cells harboring the most common KIT mutation in melanoma, and thus has therapeutic implications for acrallentiginous, chronic sun-damaged, and mucosal melanomas.
Molecular Cancer Therapeutics 09/2009; 8(8):2079-85. · 5.23 Impact Factor
