Discordance in Diagnosis of Melanocytic Lesions and Its Impact on Clinical Management.

CONTEXT.­: Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management. OBJECTIVE.­: To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management. DESIGN.­: We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not. RESULTS.­: A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients. CONCLUSIONS.­: Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified, thus, resulting in critical changes in recommendations for clinical management.

Necrotizing Granulomatous Dermatitis and Panniculitis Masquerading as T Cell Lymphoma.

A 51-year-old white woman with a past medical history significant for steroid-dependent ulcerative colitis, rheumatoid arthritis, and diabetes mellitus presented to the hospital with fever and painful, erythematous subcutaneous nodules on the medical aspects of both thighs. Histopathologic examination showed features suggestive of an abscess, but her condition failed to improve with intravenous broad-spectrum antibiotics. Molecular studies detected T cell receptor-ß gene rearrangements. The lesions later exhibited signs of necrosis, requiring multiple debridements as well as therapy with hyperbaric oxygen. She was later referred to the MD Anderson Cancer Center for evaluation for possible subcutaneous panniculitis-like T cell lymphoma.

Clinical impact of ulceration width, lymphovascular invasion, microscopic satellitosis, perineural invasion, and mitotic rate in patients undergoing sentinel lymph node biopsy for cutaneous melanoma: a retrospective observational study at a comprehensive cancer center.

The prognostic significance of the width of the ulceration in primary melanomas remains unclear, and there is a relative paucity of data for lymphovascular invasion (LVI), microscopic satellitosis (MS), perineural invasion (PNI), and mitotic rate when compared with other pathological elements currently required for reporting. To evaluate the prognostic importance of the ulceration width and other important pathologic measurements, a single-institutional retrospective study was conducted using records of cutaneous melanoma patients who underwent sentinel lymph node (SLN) biopsy at The University of Texas, MD Anderson Cancer Center between 2003 and 2008. We identified 1898 eligible patients with median tumor thickness of 1.25 mm and median follow-up of 6.7 years. By multivariable analyses, the strongest risk factor for SLN positivity was high tumor thickness followed by the presence of LVI. The pathologic measures with the strongest influence on recurrence-free survival (RFS) were tumor thickness and positive SLN status. Ulceration width and presence of MS were also significantly associated with RFS while PNI was not. Factors with the strongest influence on melanoma-specific survival (MSS) were positive SLN status and mitotic rate. In conclusion, SLN biopsy should probably be offered if the primary tumor has LVI. MS is an adverse prognostic factor for RFS, but its influence on outcome is modest. Ulceration width predicts RFS but loses its independent prognostic significance for MSS when adjusting for currently used clinicopathological factors. In view of its impact on MSS, mitotic rate should be recorded for cutaneous invasive melanomas across all T categories.

Síndrome poliglandular autoinmune tipo II: presentación de un caso / Polyglandular autoimmune syndrome type II: a case report

La afección poliglandular autoinmune constituye una rareza clínica; de todas las variantes, el síndrome poliglandular autoinmune tipo II (SPGA-II) es el más común, el cual está caracterizado fundamentalmente por la presencia de la enfermedad de Addison autoinmune combinada con tiroiditis autoinmune y diabetes mellitus tipo 1. Este síndrome ocurre fundamentalmente alrededor de la tercera y cuarta décadas de la vida, donde se reporta comúnmente en mujeres con relación a los hombres, con una proporción de 3-4:1.Objetivo: presentar un caso clínico de un síndrome de Schmidt-Carpenter.Caso clínico: paciente femenina de 35 años de edad que presenta a los 20 años diabetes mellitus tipo 1, seguida nueve años después de una tiroiditis de Hashimoto, y en los últimos cincos años amenorrea alternando con metrorragias y tres abortos espontáneos; en el ingreso hospitalario se constata alopecia y un complejo sintomático compatible con insuficiencia suprarrenal. Los estudios clínicos y analíticos comprobaron la presencia de un síndrome de Schmidt-Carpenter asociado a hipogonadismo y alopecia.Conclusiones: este síndrome es una rara enfermedad severa de múltiples glándulas endocrinas causada por trastornos inmunes con destrucción de los tejidos. El diagnóstico es clínico, comprobado por la determinación de los niveles hormonales y las pruebas de inmunidad. Se debe diferenciar de otros procesos inmunes, cromosómicos, hematológicos y digestivos que afectan diferentes glándulas y órganos. La terapéutica empleada fue eficaz. Esta enfermedad es importante para las especialidades clínicas, especialmente la medicina interna, la endocrinología, la inmunología y la genética (AU)

Polyglandular autoimmune syndrome type II is a clinical rarity; among all variants this syndrome is the most common. It is mainly characterized by the presence of autoimmune Addison´s disease combined with autoimmune thyroiditis and type I diabetes mellitus. This syndrome appears around the third and fourth decades of life. It is more frequent in women than in men, in a ratio of 3-4:1.Objective: to present a clinical case of Schmidt-Carpenter syndrome.Clinical Case: a thirty-five-year-old female patient who presented type I diabetes mellitus at the age of 20 and nine years later a Hashimoto´s thyroiditis. In the last five years the patient presented amenorrhea alternated with metrorrhagia and had three miscarriages. After her hospital admission, it was established alopecia and a symptomatic complex compatible with adrenal insufficiency. Clinical and analytical studies confirmed the presence of Shmidt-Carpenter syndrome associated with hypogonadism and alopecia.Conclusions: this syndrome is a rare and severe disease that affects multiple endocrine glands caused by immune disorders with destruction of tissues. The diagnosis is clinical, confirmed by the establishment of hormonal levels and immunity tests. This syndrome should be differentiated from other immune, chromosomal, hematological, and digestive processes that affect other glands and organs. The therapeutics employed was effective. This disease is relevant to clinical specialties, particularly for internal medicine, endocrinology, immunology, and genetics (AU)

Physical attributes and chemical composition of organic strawberry fruit (Fragaria x ananassa Duch, Cv. Albion) at six stages of ripening.

Organic strawberry fruits (Cv. 'Albion') were harvested at six different ripening stages and evaluated for physical and chemical parameters. Biometrical characteristics and moisture content did not change significantly during ripening. Total soluble solids, pH and colour development increased while titratable acidity and fruit firmness decreased 14.7% and 91%, respectively. Fructose, glucose, and sucrose followed similar tendencies. Final contents of these sugars were 2323.4, 1988.5, and 1578.4 mg/100 g. Citric, malic, and ascorbic acids followed a descending, irregular, and increasing tendency during ripening, respectively. Final contents of these acids were 822.8, 245.8, and 78.1 mg/100 g. Total anthocyanins content (TAC) increased during ripening, while the opposite was observed for total phenolic content (TPC). TAC and TPC in ripe fruit were 56.4 mg/100g and 196 mg gallic acid equivalents (GAE)/100 g. Twenty eight phenolic compounds, mainly glycosides, were identified and quantified by HPLC-DAD-MS analysis. The concentration of these compounds was ripening dependent.

Annular plaques: An unusual manifestation of graft-versus-host disease.

Chronic cutaneous graft-versus-host disease (GVHD) classically presents with lichenoid papules or sclerotic plaques. This case highlights an unusual clinical manifestation of chronic GVHD and demonstrates that the skin morphology of chronic GVHD and cutaneous lymphoma may be similar. We report for the first time a case of annular scleroderma-like graft-versus-host disease in a patient following allogeneic stem cell transplant for CD30+ anaplastic large cell lymphoma. Treatment of these skin lesions with ultraviolet A1 (UVA1) phototherapy resulted in significant improvement.

Unusual cases: melanomatosis and nephroblastomatosis treated with hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-established therapy for carcinomas, mesotheliomas, and some sarcomas. However, HIPEC has not been reported in melanomatosis or nephroblastomatosis. Here we present 2 unique cases of cytoreductive surgery and HIPEC. Cytoreductive surgery followed by HIPEC was performed in a 4-year old with melanomatosis and a 12-year old with nephroblastomatosis. A 4-year-old girl presented with leptomeningeal melanoma that metastasized from a congenital nevus. She had a ventricular peritoneal shunt placed as an infant. Melanomatosis involving the meninges and peritoneal surfaces was identified by positron emission tomographic scan imaging. Extensive plaques of melanoma were removed at the time of surgery, followed by HIPEC. She had no significant postoperative complications. Her abdomen remained free of disease 7 months after treatment. A 13-year-old girl presented with a Wilms' tumor at age 10 years. She then presented to us at the second local recurrence with multiple intraabdominal tumor implants (ie, nephroblastomatosis). We performed cytoreductive surgery followed by HIPEC. She had no postoperative complications and, at 1 year post-HIPEC, had no abdominal recurrence. We conclude that HIPEC can be performed safely for rare diseases such as melanomatosis and nephroblastomatosis. Although abdominal disease control can be realized, further systemic treatment options are necessary. A review of indications for HIPEC is included.

Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma.

PURPOSE: This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma. PATIENTS AND METHODS: Patients with stage IV or unresectable or recurrent stage III melanoma and Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. Sorafenib was given orally once or twice daily and temsirolimus was given i.v. weekly, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per Response Evaluation Criteria in Solid Tumors criteria. Consenting patients with accessible tumors underwent optional tumor biopsies before treatment and after the second infusion of temsirolimus. Tumor biopsies were analyzed for activating mutations in BRAF and NRAS, and for expression of P-extracellular signal-regulated kinase (P-ERK) and P-S6 proteins. RESULTS: A total of 25 patients were accrued to the study. The maximum tolerated doses were sorafenib 400 mg every morning and 200 mg every evening and temsirolimus 25 mg i.v. weekly. Dose-limiting toxicities included thrombocytopenia, hand-foot syndrome, serum transaminase elevation, and hypertriglyceridemia. There were no complete or partial responses with the combination; 10 patients achieved stabilization of disease as their best response. The median progression-free survival was 2.1 months. Matching pretreatment and day 15 tumor biopsies showed marked inhibition of P-S6 with treatment in 3 of 4 evaluable patients, but minimal inhibition of P-ERK. CONCLUSIONS: Combination therapy with sorafenib and temsirolimus resulted in significant toxicity at higher dose levels, failed to achieve any clinical responses in genetically unselected patient population, and did not inhibit P-ERK.

Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib.

BACKGROUND: Keratoacanthomas, as well as an actinic keratosis progressing to squamous cell cancer, have been reported in patients who were treated with sorafenib, a multikinase inhibitor known to suppress the actions of Raf kinase and vascular endothelial growth factor receptor. OBSERVATIONS: We describe a 70-year-old white woman with metastatic renal cell carcinoma who was treated with a combination of sorafenib and tipifarnib (a farnesyltransferase inhibitor). She had no history of skin cancer. However, within 3 months after starting this therapy, she developed 3 erythematous nodules on her legs. Pathologic examination showed deeply invasive, well-differentiated squamous cell carcinomas. The tumors were excised, and sorafenib-tipifarnib treatment was discontinued. No new lesions have developed to date. CONCLUSIONS: Targeted agents, such as sorafenib and tipifarnib, are increasingly being used in the management of visceral malignant neoplasms. A temporal relationship was observed between the initiation of the targeted treatments and the emergence of these cutaneous cancers. Further study of the mechanisms responsible for the rapid appearance of squamous cell cancers in this setting may provide insights into the pathogenesis of skin tumors.

Sentinel lymph node biopsy for sebaceous cell carcinoma and melanoma of the ocular adnexa.

OBJECTIVE: To provide clinical details and long-term outcome data for a series of patients with eyelid or conjunctival melanoma or eyelid sebaceous cell carcinoma who underwent sentinel lymph node (SLN) biopsy. DESIGN: Retrospective interventional case series with review of clinical records and pathologic specimens. SETTING: Tertiary comprehensive cancer center. PATIENTS: Twenty-five consecutive patients treated at 1 institution for eyelid or conjunctival melanoma or eyelid sebaceous cell carcinoma from December 2000 to October 2004. INTERVENTIONS: Surgical removal of the eyelid or conjunctival tumor and SLN biopsy. MAIN OUTCOME MEASURES: Local treatment modalities; lymphatic basins in which SLNs were identified; status of SLNs; false-negative rate; and long-term patterns of local recurrence, regional and distant metastasis, and survival. RESULTS: Seven patients had conjunctival melanoma, 8 had eyelid-margin melanoma with a considerable palpebral conjunctival component, and 10 had eyelid sebaceous cell carcinoma. The SLNs were identified in all but 1 patient by using technetium Tc 99m sulfur colloid as a tracer. Intraoperatively, in 16 patients in whom blue dye was used in addition to technetium Tc 99m sulfur colloid during mapping, no SLN was blue. One patient with conjunctival melanoma and 1 patient with eyelid melanoma had a histologically positive SLN. Two patients with eyelid melanoma and 2 patients with eyelid sebaceous cell carcinoma had negative findings from SLN biopsy but developed recurrence in their regional lymph nodes during the follow-up period. Overall, during follow-up, 2 of 10 patients with sebaceous cell carcinoma (20%) and 5 of 15 patients with eyelid or conjunctival melanoma (33%) had regional lymph node metastasis. Four patients with melanoma who had regional metastasis also developed distant organ metastasis. Two patients with sebaceous cell carcinoma--1 with regional metastasis and 1 without--developed distant organ metastasis. CONCLUSIONS: The detection of histologically positive SLNs in this series of patients may justify further study of SLN biopsy for high-risk patients with ocular adnexal melanoma or eyelid sebaceous cell carcinoma. The false-negative rate is higher than that reported for SLN biopsy at most other anatomic sites. Patients with negative findings from SLN biopsy still require careful long-term follow-up because they may develop regional or distant metastasis.

Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck.

OBJECTIVE/HYPOTHESIS: Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence. STUDY DESIGN: Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center. METHODS: Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality. RESULTS: Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls. CONCLUSIONS: Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.

Effects of intense pulsed light and the 1,064 nm Nd:YAG laser on sun-damaged human skin: histologic and immunohistochemical analysis.

BACKGROUND: Nonablative methods may produce collagen synthesis in sun-damaged skin. OBJECTIVE: To study the effects of intense pulsed light (IPL) and 1,064 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser: a histologic and immunohistochemical analysis of sun-damaged skin. MATERIALS AND METHODS: Nine subjects participated. Five subjects received five-monthly treatments with IPL (560 nm cutoff filter, 8 x 35 mm spot size, pulse duration 2.4/4.2 milliseconds, pulse delay 15 milliseconds, fluence 28-35 J/cm2). Four subjects received treatment with a 1,064 nm Nd:YAG laser (130 J/cm2, triple pulse, 7.0/7.0/7.0-millisecond pulse duration, 75-millisecond delay). Routine histology and immunohistochemistry on 2 mm punch biopsies were taken before treatment and then at 3 and 6 months. We quantified collagen in the upper dermis and expression of heat shock protein 70 and procollagen 1. RESULTS: Pretreatment specimens contained solar damage. After treatment with the 1,064 nm Nd:YAG laser, the amount of collagen in the papillary dermis was slightly thicker than in those subjects treated with the IPL device (nonsignificant differences). Scattered dendritic cells in the papillary and upper reticular dermis expressed heat shock protein 70 and procollagen 1 after treatment with either light device. CONCLUSION: Both the IPL and 1,064 nm Nd:YAG laser-induced heat activation of superficial dermal dendritic cells resulted in deposition of collagen in the papillary dermis without evident morphologic damage to the epidermis or dermis.

Effects of intense pulsed light on sun-damaged human skin, routine, and ultrastructural analysis.

BACKGROUND AND OBJECTIVE: New, non-ablative methods can be used in skin rejuvenation. Histologic analysis of non-ablative IPL effects on facial, sun-damaged skin. STUDY DESIGN/MATERIALS AND METHODS: Five female subjects, wrinkle class I or II and Fitzpatrick skin types I, II, and III. IPL treatment: once monthly, 560-nm cut-off filters, spot size 8x35 mm, 28-36 J/cm. Routine histology or electron microscopy on 2-mm punches, before treatment and then 1 week, 3 months, and 12 months. RESULTS: Pre-treatment specimens contained solar elastosis and perifollicular lymphoid infiltrates. Collagen and elastic fibers appeared unaffected by treatment. At 1-week, Demodex organisms appeared coagulated. CONCLUSIONS: Under these conditions, IPL induces minimal morphologic changes in mildly sun-damaged skin. Some esthetic improvement may be secondary to clearing of Demodex organisms and reduction of associated lymphocytic infiltrate.