Rafael Fantelli Stelini

Seminal vesicle invasion in radical prostatectomies: Which is the most common route of invasion?

Introduction Very few studies have been published on seminal vesicle invasion (SVI), and these have obtained conflicting results. The aim of the present investigation was to determine the most frequent of three possible routes of seminal vesicle invasion: (1) extraprostatic extension (EPE) into soft tissue adjacent to the seminal vesicle and then into the wall of the seminal vesicle, (2) invasion via the sheath of the ejaculatory duct, penetrating the muscular wall of the ejaculatory duct or extending up the ejaculatory duct into the seminal vesicle muscle wall, or (3) discontinuous metastases.Materials and methodsThe surgical specimens of 230 consecutive patients submitted to radical prostatectomy were histologically evaluated by complete embedding and whole-mount processing.ResultsOf the surgical specimens obtained from 230 patients, 28 (12.17%) showed the presence of either unilateral or bilateral SVI. The routes of SVI in these 28 specimens were: (1) only via the sheath of the ejaculatory duct (0/28; 0%); (2) discontinuous metastases (3/28; 11%), (3) both EPE and via the sheath of the ejaculatory duct (6/28; 21%), and (4) only EPE (19/28; 68%). One-half (14/28; 50%) of the 28 seminal vesicles involved had unilateral invasion and, in most of these cases (42.85%), EPE was unilateral and ipsilateral.ConclusionOur results suggest that the most important and most frequent route of SVI is extraprostatic extension of prostate carcinoma into the soft tissue adjacent to the ipsilateral seminal vesicle and then into the wall of the seminal vesicle.

Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas

Cyclooxygenase 2 (COX-2) and phosphorylated Akt1 (p-Akt1) are associated with tumor spreading, cell proliferation, high metabolism, and angiogenesis in solid tumors. This study aimed to investigate COX-2 and p-Akt1 expression in primary and metastatic melanomas by correlating with the cellular proliferation index (as revealed by minichromosome maintenance 2 expression) and the outcome of patients with malignant melanomas. Seventy-seven biopsies of malignant melanomas, including 42 primary nonmetastatic melanomas (PNMMs), 12 primary metastatic melanomas (PMMs), and 23 metastatic melanomas (MMs), were retrospectively selected. Tissue microarrays were developed and submitted for immunohistochemical staining for COX-2, p-Akt1, and minichromosome maintenance 2. Increased COX-2 cytoplasmic staining patterns were observed in PMM and MM when compared with PNMM (P=0.0011). Higher nuclear and cytoplasmic expression of p-Akt1 was more closely associated with PMM than with MM and PNMM (P<0.00001). Coexpression of these biomarkers was closely correlated with lower overall survival rates in melanomas. Furthermore, we observed a statistically significant positive correlation between the mitosis index and increased COX-2 expression (P=0.0135) and between p-Akt1 (P=0.0038) and the cellular proliferation index (P=0.0060). Taken together, our findings demonstrate that COX-2 and p-Akt1 play an important combined role during melanoma progression and are associated with highly metastatic tumors and survival rates in patients with MM. In addition, these biomarkers can be used to predict melanoma prognosis independently of metastatic status. However, further studies are required to elucidate the biological role of these biomarkers during the progression of MM events.

Granuloma Faciale and Eosinophilic Angiocentric Fibrosis: Similar Entities in Different Anatomic Sites.

Background: Eosinophilic angiocentric fibrosis (EAF) and granuloma faciale (GF) share several histopathologic features, including eosinophil-rich inflammation, microangiitis, and progressive fibrosis. Concurrent presentation of EAF and GF suggests a pathogenetic link between them. Objectives: To identify histologic findings that tell them apart and construe the pathogenetic mechanisms behind each morphologic variable, 14 immunohistochemical markers were used to study the cells subpopulations in 14 cases of GF and 3 cases of EAF. Materials and Methods: The lesions were classified according to their stage of development. The antibodies studied were: CD4, Foxp3, CD8, granzymes A and B, perforin, granulysin, CD20, CD56, CD68, ICAM-1, CD34, CD105, and 1A4. Results: The intensity of the sclerotic response and the density of 1A4-immunostained cells were significantly higher in EAF. In both diseases, CD68+ cells were the most numerous, followed by CD20+, CD8+, and CD4+ cells. About 30% of cells expressed ICAM-1. Among cells with cytotoxic granules, granulysin-positive cells were the most frequent. Conclusions: Differences between GF and EAF were found to be mostly like due to anatomic site (usually skin of the face vs. sinonasal cavity) and stage of the disease development (usually earlier in cutaneous lesions because of their visibility). Innate and adaptive immunity, including B cells, T cells, and cytotoxic granules have a role in their pathogenesis.

Lower energy and pulse stacking. A safer alternative for skin tightening using fractional CO2 laser.

PURPOSE To evaluate the effect of different energies and stacking in skin shrinkage. METHODS Three decreasing settings of a fractional CO2 laser were applied to the abdomen of Twenty five Wistar rats divided into three groups. Group I (n=5) was histologically evaluated for microthermal zones dimensions. Groups II and III (n=10 each) were macroscopic evaluated with freeware ImageJ for area contraction immediately and after 30 and 60 days. RESULTS No statistical significance was found within microthermal zone histological dimensions (Group I) in all settings studied. (Ablation depth: 76.90 to 97.18µm; Coagulation depth: 186.01 to 219.84 µm). In Group II, macroscopic evaluation showed that all settings cause significant immediate skin contraction. The highest setting cause significant more intense tightening effect initially, contracting skin area from 258.65 to 179.09 mm2. The same pattern was observed in Group III. At 30 and 60 days, the lowest setting significantly sustained contraction. CONCLUSION Lower fractional CO2 laser energies associated to pulse stacking could cause consistent and long lasting tissue contraction in rats.

p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation.

Multistep carcinogenesis involves loss of function of tumor suppressor proteins such as p53 and induction of angiogenesis. Such mechanisms contribute to cutaneous squamous cell carcinoma progression and may be interconnected. We aimed to explore p53 immunoexpression in spectral stages of cutaneous squamous cell carcinoma and correlate expression to both neovascularization and cellular proliferation. We estimated the percentages of immunostained cells for p53 and Ki67 (proliferation marker) in three groups: 23 solar keratoses, 28 superficially invasive squamous cell carcinomas and 28 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by neoangiogenesis (CD105) immunomarker in each group. There was no significant difference for rate of p53- and Ki67-positive cells between groups. Significant positive correlation was found between the CD105 microvascular area and the rate of p53 positive cells in superficially invasive squamous cell carcinoma as well as between the rate of p53- and Ki67-positive cells in invasive squamous cell carcinoma. p53 and Ki67 immunoexpression did not increase with cutaneous squamous cell carcinoma progression. Neovascularization in the initial stage of invasion and proliferative activity in the frankly invasive stage were both associated with p53 immunoexpression. Loss of p53 tumor suppressor function through progressive steps may be directly involved in skin carcinogenesis.

Cutaneous metastasis as the first manifestation of occult malignant breast neoplasia

Cutaneous metastases from primary internal malignancies represent 0.7-9% of patients with cancer. We report a 65-year-old female patient referred for evaluation of normochromic papules on the trunk and upper limbs that had been present for three months. A skin biopsy revealed diffuse cutaneous infiltration by small round cell tumors. Immunohistochemistry was positive for AE1/AE3, CK7, estrogen receptor and mammaglobin. The final diagnosis was cutaneous metastasis of occult breast cancer, since the solid primary tumor was not identified. The location of the primary tumor can not be determined in 5-10% of cases. In these cases, 27% are identified before the patient’s death, 57% at autopsy, and the remaining 16% can not be located.

Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma: Similar Morphology but Different Pathogenesis.

Abstract Differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is difficult due to their similarities. The mechanisms that drive their distinct biological behavior are poorly understood. To investigate whether the assessment of microvessel density (MVD) could be helpful in KA and SCC differential diagnosis and to gain insight into the pathogenesis of KA-like neoplasms, we compared the density of CD105- and CD34-stained vessels in KAs and SCCs and their relation to the expression of the p53 oncoprotein and proliferation marker Ki67. This is an observational retrospective cohort study. Forty lesions with clinical appearance of KAs (29 KAs and 11 SCCs) entered the study. A biopsy was taken from each lesion at presentation and the natural clinical course was monitored for at least 1 month. Growing or minimally regressing lesions were submitted to complete surgical excision. The diagnoses were established on combined clinical, histological, and follow-up evaluations. The MVD and p53 or Ki67 expression in neoplastic cells were assessed through morphometry. The MVD did not show discriminating power between KAs and SCCs. The Ki67 proliferation rate was significantly higher in SCCs. Although neoangiogenesis (CD105-MVD) in KAs was associated with cell proliferation, in SCCs it was not. There was significant correlation between p53 expression and neoplasia size in SCCs but not in KAs. From our results, we may conclude that KA and SCC have similarities, as CD105- and CD34-MVD. However, the low Ki67 proliferation index and the positive correlation between Ki-67 index and neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to involvement of distinct pathogenesis.

Additional thoughts about juvenile hyaline fibromatosis and infantile systemic hyalinosis.

To the Editor: We read with interest the review article by Thway et al,1 specifically on the topic juvenile hyaline fibromatosis (JHF)/infantile systemic hyalinosis (ISH), and we have the following comments to offer: As reported by the authors,1 in recent years, JHF and ISH have been described as different degrees of severity of the same disease, and hence some unifying terms have been proposed.2,3 As in the systemic hyalinosis nomenclature,2 the term “systemic” excludes several JHF/ISH patients with localized disease.3,4 We support4 the adoption of another unifying terminology [hyaline fibromatosis syndrome (HFS)] proposed by Nofal et al3 and subsequently adopted by others.5 HFS is a broader term that seems to make the clinicopathologic correlation to properly diagnosing patients in a clearer and simpler way.3,4 Moreover, instead of describing ISH as a more severe spectrum and JFH as the milder spectrum,1 HFS patients can be divided into mild, moderate, severe, and lethal subtypes according to the severity grading system initially proposed by Nofal et al3 and recently modified by our group.4 This grading system seems to show the complexity of this disease more accurately and it also has direct implications on the management of HFS patients.4 According to our study4 those by and others,2,5,6 lesions usually appear earlier (within the first year of life) than the age (2 to 5 y old) described in the review,1 and the domain of this knowledge is important for a correct diagnosis to be made early in the course of the disease.6 After identifying the anthrax toxin receptor-2 (ANTXR2) gene as being responsible for FHJ/ISH as described in the review,1 attempts were made for a genotype-phenotype correlation.7 In our study,4 we evaluated 28 different mutations and the respective patients but found no relationship between genotype and severity of clinical data, suggesting that other modifying genes and/or environmental factors may also play important roles. Histologically, besides the aspects discussed by the authors,1 in cutaneous and gingival lesions the proliferation of spindle cells without atypia forming strands in the midst of homogenous and hyaline eosinophilic material that is more abundant in areas of less cellularity and denser around certain blood vessels has been described.4,8,9 In certain areas, fusocellular cords can be close to clear slits, simulating vascular spaces, or otherwise can exhibit clear pericellular halos (so called “chondroid appearance”).4,9,10 In addition, electron microscopy evaluation can reveal a banding pattern with expanded Golgi complexes that are filled with a microfibrillar and fine granular layer,8 and the analysis of stratum spinosum can show big spaces between the adjoining cells and significant decrease of the interdigitating processes.11 The presence of calcospherules (calciumcontaining lamellar bodies) has also been described,9 suggesting that they may represent calcification of fibrillogranular material within the multivesicular bodies and constituting a helpful diagnostic marker for the disease.9 Currently, there is no satisfactory treatment for this stigmatizing, debilitating, and potentially lethal disease.2–5 With regard to the treatment approach adopted by the authors,1 surgical excisions have been considered the main form for managing both skin and oral lesions,4,11 but not for joint, bone, and visceral involvement. There is disagreement about the time of initiation of the surgical approach; some authors2,10 are in favor of an intervention soon after the onset of lesions, whereas others4,12 are in favor of a later treatment. At present, our group4 is following up 4 of the 5 HFS patients previously reported. Their lesions are resected only when they become ulcerated (risk of infection) or present with some aesthetic and/or functional conditions, because the lesions may recur after excision and multiple attempts at treatment can sometimes be as crippling as the disease itself. Finally, as some studies5,13 have found potential targets for pharmacological intervention to achieve more radical and effective treatments, future genetic studies should focus their efforts in the development of potential genetic therapies for this devastating disorder. Rafael Denadai, MD* Debora Romeo Bertola, MD, PhDw Rafael Fantelli Stelini, MDz Cassio Eduardo Raposo-Amaral, MD* *Institute of Plastic and Craniofacial Surgery, Hospital de Crânio e Face SOBRAPAR zDepartment of Anatomic Pathology Universidade Estadual de Campinas Campinas wGenetics Unit, Department of Pediatrics Universidade de São Paulo São Paulo, Brazil

Histomorphometric approach to differentiate skin lesions of tuberculoid leprosy from sarcoidosis.

More than 200 000 new cases of leprosy are detected worldwide annually. Physicians commonly have difficulty in differentiating tuberculoid form of leprosy (TL) from sarcoidosis’ cutaneous manifestation.

Liquid silicone used for esthetic purposes as a potentiator for occurrence of post-radiotherapy genital lymphedema: case report.

CONTEXT: Lymphedema consists of extracellular fluid retention caused by lymphatic obstruction. In chronic forms, fat and fibrous tissue accumulation is observed. Genital lymphedema is a rare condition in developed countries and may have primary or acquired etiology. It generally leads to urinary, sexual and social impairment. Clinical treatment usually has low effectiveness, and surgical resection is frequently indicated. CASE REPORT: We report a case of a male-to-female transgender patient who was referred for treatment of chronic genital lymphedema. She had a history of pelvic radiotherapy to treat anal cancer and of liquid silicone injections to the buttock and thigh regions for esthetic purposes. Radiological examinations showed signs both of tissue infiltration by liquid silicone and of granulomas, lymphadenopathy and lymphedema. Surgical treatment was performed on the area affected, in which lymphedematous tissue was excised from the scrotum while preserving the penis and testicles, with satisfactory results. Histopathological examination showed alterations compatible with tissue infiltration by exogenous material, along with chronic lymphedema. CONCLUSION: Genital lymphedema may be caused by an association of lesions due to liquid silicone injections and radiotherapy in the pelvic region. Cancer treatment decisions for patients who previously underwent liquid silicone injection should take this information into account, since it may represent a risk factor for radiotherapy complications.