Cost analysis of sentinel lymph node biopsy in melanoma.

INTRODUCTION AND OBJECTIVE: Sentinel lymph node biopsy (SLNB) is the most useful tool for node staging in melanoma. SLNB facilitates selective dissection of lymph nodes, that is, the performance of lymphadenectomy only in patients with sentinel nodes positive for metastasis. Our aim was to assess the cost of SLNB, given that this procedure has become the standard of care for patients with melanoma and must be performed whenever patients are to be enrolled in clinical trials. Furthermore, the literature on the economic impact of SLNB in Spain is scarce. METHOD: From 2007 to 2010, we prospectively collected data for 100 patients undergoing SLNB followed by transhilar bivalving and multiple-level sectioning of the node for histology. Our estimation of the cost of the technique was based on official pricing and fee schedules for the Spanish region of Murcia. RESULTS: The rate of node-positive cases in our series was 20%, and the mean number of nodes biopsied was 1.96; 44% of the patients in the series had thin melanomas. The total cost was estimated at between €9486.57 and €10471.29. Histopathology accounted for a considerable portion of the cost (€5769.36). DISCUSSION: The cost of SLNB is high, consistent with amounts described for a US setting. Optimal use of SLNB will come with the increasingly appropriate selection of patients who should undergo the procedure and the standardization of a protocol for histopathologic evaluation that is both sensitive and easy to perform.

[The value of laminin-322 staining in distinguishing between keratoacanthoma, keratoacanthoma with areas of squamous cell carcinoma, and crateriform squamous cell carcinoma]. / Utilidad de la tinción con laminina-332 para diferenciar queratoacantoma, queratoacantoma con áreas de carcinoma epidermoide y carcinoma epidermoide crateriforme.

INTRODUCTION: Keratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs. MATERIAL AND METHODS: Seventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322. RESULTS: Laminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC. CONCLUSIONS: Laminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC.

[Immunohistochemical staining of p16 in squamous cell carcinomas of the genital and extragenital area]. / Tinción inmunohistoquímica p16 en carcinomas epidermoides del área genital y extragenital.

BACKGROUND AND OBJECTIVES: Positive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or αsubtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC. MATERIAL AND METHODS: Paraffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR). RESULTS: In the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages. CONCLUSIONS: According to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.

[Solar elastosis in cutaneous squamous cell carcinoma]. / Elastosis solar en carcinomas espinocelulares cutáneos.

INTRODUCTION: Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. MATERIAL AND METHODS: We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. RESULTS: Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. CONCLUSIONS: Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both.

Hepatic angiosarcoma. Presentation of two cases.

Hepatic angiosarcoma is a rare primary tumor of the liver with a mesenchymal origin. Diagnosis is difficult because clinical manifestations and imaging studies are inconclusive. In many cases a diagnosis is obtained during necropsy, not being apparent during the course of disease. It is associated with several risk factors, but these contribute to explaining only a few of all reported cases. When clinical manifestations begin progression is often fast, and possibilities for curative treatment are limited.We report two cases of hepatic angiosarcoma. In the first one, our patient had an insidious initial course, and then suddenly presented with hepatic failure followed by acute respiratory distress. A diagnosis was reached during necropsy. In the second case, we initiated the study of a chronic liver disease using fine-needle aspiration biopsy, which showed findings suggestive of hepatic angiosarcoma. In the following weeks the patient started on a torpid clinic course, and died from multiple organ failure.

Mitotic rate as an important prognostic factor in cutaneous malignant melanoma.

BACKGROUND: Recently, the quantification of mitoses in cutaneous melanoma has been discharged from the main prognostic variables of the TNM classification. OBJECTIVE: To investigate the prognostic value of the presence of mitoses in primary cutaneous melanoma and to establish the number of mitoses per mm2 that may have prognostic significance. METHODS: A retrospective observational study was performed on 141 patients treated for cutaneous melanoma, who were assessed by the same pathologist, and who had a minimum follow-up of 2 years. Clinical, epidemiological, histopathological and follow-up variables were gathered and compared with the number of mitoses to distinguish the significance of differences by means of univariate, multivariate, and survival analyses. RESULTS: The cut-off level related to a better sensitivity and specificity was 1.50 mitoses per mm2. The presence of two or more mitoses/mm2 showed a better relationship with prognostic variables and both the overall and disease-free survival than the presence of 1 or more mitoses/mm2. This happens especially in melanomas thicker than 0.8 mm and it could affect the staging in cases with Breslow between 1 and 2 mm. CONCLUSIONS: A mitotic rate of two or more mitoses per mm2 in cutaneous melanoma should be considered as a more accurate prognostic factor than one or more mitoses per mm2, particularly in tumors equal or greater than 0.8 mm in thickness.

Tumor suppressor SET9 guides the epigenetic plasticity of breast cancer cells and serves as an early-stage biomarker for predicting metastasis.

During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.

Extramammary Paget's disease of the breast: an unusual location with prognostic implications.

Extramammary Paget's disease is a neoplastic process of intraepidermal origin; its management and prognosis are very different from those of mammary Paget's disease. We present a case of extramammary Paget's disease located in the breast. This is an exceptional location, whose differential diagnosis is important because of its therapeutic and prognostic implications.

Palpable breast lesions: utility of Doppler sonography for diagnosis of malignancy.

This study was designed to find whether there are any differences between benign and malignant palpable breast lesions as they are seen on grey-scale and colour-Doppler and on power-Doppler sonography; to determine which variables for each technique are most helpful in distinguishing any such differences; and to see whether the use of an echo-enhancing agent gives better results in the differential diagnosis. Forty-five palpable breast lesions (16 benign and 29 malignant) were evaluated in a preoperative study using grey-scale sonography, colour-Doppler sonography and power-Doppler sonography before and after administration of an echo-enhancing agent (Levovist). We reached the following conclusions: (1) In the grey-scale ultrasound study of palpable breast lesions the presence of microcalcifications, acoustic shadowing and non-well-defined margins are related to malignancy. (2) Colour- and power-Doppler sonography may help in the differential diagnosis. (3) The use of an echo enhancer (Levovist) accentuates these differences and enables them to be noted in other variables, such as pulsatility index, nodule-to-vascularity ratio and number of poles.

Salivary duct carcinoma: clinicopathological and immunohistochemical studies.

Nine cases of salivary duct carcinoma were reviewed clinically, histologically and immunohistochemically, with special evaluation of biomarkers with prognostic significance (p53, Ki67, c-erbB-2 and DNA content). Eight tumours occurred in the parotid gland and one in the submandibular gland. The average age of the patients (8 males and 1 female) was 62.8 years (range = 47-74 years). Tumour size ranged from 1 to 6 cm (mean = 3.46 cm). Recurrences were found in 33.3% (3 patients), regional metastases in 44.4% (4 patients) and systemic metastases in 33.3% (3 patients). Three patients died of their disease (median survival = 12.3 months), one is alive with the disease (follow-up of 222 months) and 5 are alive without evidence of disease (mean follow-up of 75 months). p53 protein nuclear immunostaining was positive in 66.6% and c-erbB-2 overexpression was observed in 100% of the tumours. Ki 67 positivity ranged from 6.75% to 47.5% of tumour cells (mean = 21.3%). DNA aneuploidy was found in 4 tumours (44.4%) and DNA diploidy in 5 (55.5%). Our results seem to indicate that Ki67 immunostaining can be useful in the evaluation of the biological behaviour of these tumours, as well as the presence of a high proliferative index of aneuploid cells and the presence of distant metastases.

[Selective sentinel node biopsy in melanoma using preoperative lymphoscintigraphy location and intraoperative detection gamma probe]. / Biopsia selectiva del ganglio centinela en el melanoma mediante localización con linfogammagrafía preoperatoria y sonda de detección gamma intraoperatoria.

BACKGROUND: The experience in detection of sentinel lymph node in melanoma using preoperative scintigraphy and intraoperative gamma probe is referred. PATIENTS AND METHODS: We studied 60 patients with stage I-II melanoma who underwent sentinel lymph node biopsy performed using 99m-Tc-labelled sulphur colloid as radioactive tracer. A preoperative scintigraphy was performed and intraoperative gamma probe was used to localize the sentinel node in all cases. Scintigraphy results, effectiveness of intraoperative detection (technical efficacy), pathological results, and follow-up have been studied. RESULTS: Preoperative detection was 98.3% and the mean basin detected was 1.17. There were multiple basins especially when melanomas were on the trunk. Technical efficacy was 98.4% and intraoperative detection was more difficult in parotid gland region. HMB-45 immunohistochemical staining was essential in pathological studies, in whom 10% were positives. Lymphadenectomy could be avoided in 90% of the patients. Recurrences were not detected during follow-up and metastases were found only in non biopsied cases. Sentinel node biopsy morbidity was significative lesser than that of lymphadenectomy. CONCLUSIONS: Preoperative scintigraphy and intraoperative gamma probe use to localize sentinel node in melanoma have a high efficacy. They can reveal multiple basins and they allow a more selective surgical approach and a minimal dissection.

[Malignant neoplasms of the penis]. / Neoplasias malignas del pene.

OBJECTIVE: To assess the behaviour and management of these uncommon neoplasias. MATERIAL AND METHODS: Between March 1975 and July 1999, a total of 95 malignant neoplasias of the penis were diagnosed and treated by our unit. Patients mean age was 62 years (28 to 87 years). A retrospective analysis of any associated lesions, biological behaviour of the various neoplasias, as well as therapies used is carried out. RESULTS: The squamous carcinoma of the penis (SCP) is the most frequent pathohistological entity entailing 78 cases (82%), followed by verrucous carcinoma (VC) 13 cases (13.5%), basal cells carcinoma 1 case, and melanoma, lymphoma and penile metastasis 1 case each. There is a significant presence of associated lesions with marked predominance of phimosis. The most frequent reason for the call is an injury of the penis (74 cases; 78%). Treatment was mainly partial penectomy (51 patients; 53.7%), followed by conservative treatment in 28 cases (30%). Inguinal lymphadenectomy was performed in 13 patients (14%), due to either a positive nodular biopsy or a persistent adenopathy following antibiotic therapy. CONCLUSIONS: Neoplasias showing superior biological behaviour are basal cell carcinoma of the penis, and verrucous carcinoma. Prognosis in SCP is based on pathological status and node involvement. Patients with pT1 tumours showed no metastatic adenopathies after follow-up regardless of cytological grading, and are therefore candidates to watchful waiting with regular monitoring. Melanoma of the penis is a highly aggressive tumour due to its high metastatic capacity with a poor prognosis.

[Intraperitoneal bladder perforation in emphysematous cystitis]. / Perforación vesical intraperitoneal en el transcurso de una cistitis enfisematosa.

Contribution of one case report of a 69-year old diabetic male patient with neurogenic bladder. The patient developed emphysematous cystitis and peritonitis secondary to intraperitoneal perforation of the bladder. Emphysematous cystitis is an uncommon clinico-radiologic entity more frequent in diabetic and female patients and the elderly. Early diagnosis and treatment may avoid a fatal outcome. The paper includes a review of this condition.