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The histopathologic evolution of recurrent herpes simplex labialis.

In a study of the natural history of recurrent herpes simplex labialis, we examined hematoxylin and eosin-stained sections of biopsies taken from lesions at various clinical stages. The earliest specific findings which could be recognized were changes within the epidermal cell nuclei, including peripheral clumping of chromatin, development of homogeneous "ground glass" appearance, and ballooning of nuclei. Eosinophilic intranuclear inclusion bodies were unusual and occurred in late lesions. Vacuolization was the earliest cytoplasmic alteration within keratinocytes. The herpes-induced changes began focally along the basal cell layer, but the entire epidermis was rapidly altered. Pilosebaceous units were commonly affected. Within the dermis, no cells with typical herpesvirus-induced changes were seen. In early lesions, mononuclear and polymorphonuclear inflammatory cells were equally prominent; in later lesions neutrophils were most numerous. Histopathologic changes of recurrent herpes simplex begin multicentrically within the epidermis and are present prior to the onset of physical findings.

Biopsy↗

Inverted papilloma: an analysis of 87 cases.

A group of 87 patients with inverted papilloma, a locally aggressive benign sinonasal tumor, were treated over the past 15 years. Selection of therapy depends on an accurate radiographic assessment of the extent of tumor. The tumor's local aggressiveness, high rate of recurrence, associated malignancy, and multicentric tendency have led most workers to advocate radical surgical removal of the tumor by lateral rhinotomy and en bloc resection of the ethmoid labyrinth. Radiographic evaluation by computed tomography scanning and magnetic resonance imaging permits identification of a small group of patients who have limited lesions and may be candidates for conservative tumor resection by intranasal or transantral sphenoethmoidectomy. Among our ten patients treated with conservative surgery, there was recurrence in one case (10%). Seventy-five patients underwent rhinotomy and medial maxillectomy, with seven cases recurring (9%). The overall recurrence rate was 9% (8 of 87). Among the 87 cases, 5 patients had carcinoma (6%). The literature is reviewed and the principles of case selection and management are discussed.

Adolescent↗

Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves.

HYPOTHESIS: The clinical significance of hepatectomy for hepatocellular carcinoma (HCC) is still controversial because of frequent intrahepatic recurrence, which results from either recurrence due to residual intrahepatic metastasis (Rim) or recurrence due to metachronous, multicentric liver carcinogenesis (Rmc). DESIGN: Retrospective review. Disease-free survival curves were obtained by the Kaplan-Meier method and the rates of Rim and Rmc were analyzed using 2 regression lines, based on the evidence that Rmc occurs at a constant rate throughout follow-up, whereas Rim occurs only in the early postoperative period. SETTING: University hospital. PATIENTS: From 1980 to 1996, 241 patients with HCC who underwent curative hepatic resection. MAIN OUTCOME MEASURE: Intrahepatic recurrence. RESULTS: Disease-free survival curves for all patients in the early (within 2 years) and late (4 years after surgery) follow-up were approximated by 2 regression lines, which represent both Rim and Rmc (Y(1) = -3.4X + 48) and only Rmc (Y(2) = -23.1X + 98). Using this approximation, the annual incidence of Rim within 2 years (a(1)-a(2)) was calculated as 19.7% and that of Rmc (a(2)) was 3.4%. The ratio of Rim in tumor recurrence (b(1)-b(2)) was 50%, and that of Rmc (b(1)) was 48%. The ratios of Rmc in patients with stages I and II HCC were 60% and 64%, respectively. In contrast, the values could not be calculated in patients with stages III and IVA because all but 2 patients showed recurrence within 4 years after surgery. CONCLUSION: Tumor recurrence is estimated to result from metachronous liver carcinogenesis in 48% of hepatectomized patients with HCC.

Carcinoma, Hepatocellular↗

[Causes of recurrence of patients with chromaffin tumors].

From 1957 to 2001, 520 patients with pheochromocytomas were operated. Two hundred and sixty patients were followed up from 4 to 21 years (8.4 +/- 1.9 years on the average). Complaints of 83 (31.9%) patients were similar to those before removal of the primary tumor. There was no evidence of tumors in 34 patients. Chromaffin tumors were revealed in 49 (18.9%) patients with clinical symptoms of hypercatecholaminemia. In 27 (55.1%) cases contralateral tumors were detected, in 11 of 27--the disease was familial. Extraadrenal chromaffin tumors occurred in 6 (12.2%) patients. In 8 of 49 (16.3%) patients recurrent clinical symptoms resulted from metastasis, malignant tumor after the first operation was diagnosed morphologically only in 6 of them. True recurrence of tumor at the in site of primary operation was recorded in 8 (16.3%) patients, including in 2 patients with MEN-2 in multicentric but benign tumor. Thus, true recurrence was diagnosed in 6.15% of 260 patients. True recurrence is most probable in multicentric tumor, when the tumor involves adjacent organs and tissues, and in vascular emboli in great vessels.

Adrenal Gland Neoplasms↗

Human papillomavirus type 16 in vulvar carcinoma, vulvar intraepithelial neoplasia, and associated cervical neoplasia.

Vulvar intraepithelial neoplasia (VIN) is becoming more widespread and the patients are becoming still younger. Although progression to invasive vulvar carcinoma is uncommon, local recurrences are frequent and about one-quarter of the patients have multicentric genital disease. The aim of the present study was to search for a possible significant association of human papillomavirus (HPV) infection with vulvar carcinoma, recurrences, and multicentric disease. We used the polymerase chain reaction to examine vulvar and cervical biopsies from 43 patients with vulvar neoplasia for HPV type 16, which is the subtype most often detected in genital malignant or premalignant lesions. HPV 16 DNA sequences were found in 14 of 24 (58%) vulvar squamous carcinomas and in 15 of 19 (79%) VIN lesions. Nine patients (21%) had associated cervical neoplasia and six of these harbored HPV 16 in both lesions. Patients with recurrent intraepithelial neoplasia had a significantly higher incidence of HPV 16-positive lesions. No association was found with regard to the occurrence of multicentric disease or risk of malignant progression.

Adult↗

Partial nephrectomy: technique, complications and pathological findings.

PURPOSE: We evaluate whether partial nephrectomy can be performed safely and efficaciously for renal tumors. MATERIALS AND METHODS: The results of 67 partial nephrectomies performed between 1977 and 1994 for renal cell carcinoma (51), oncocytoma (9), angiomyolipoma (3), transitional cell carcinoma (3) and other nonneoplastic lesions (2) were analyzed retrospectively in detail. RESULTS: Diminished complication rates were noted after 1988, and were attributed to improvements in surgical technique and an increased incidence of smaller, serendipitously discovered tumors. Although 35.5% of the patients had preoperative renal impairment (mean serum creatinine 2.1 mg./dl.), there were minimal changes in renal function and no patient required acute hemodialysis following partial nephrectomy. Among 42 patients with clinical stage T1 to T2 renal cell carcinoma undergoing partial nephrectomy local recurrence was identified in 8.3% of those with primary neoplasms. All 6 patients with local recurrence had negative surgical margins, recurrence often, distant from the operative site and multifocal disease, implicating multicentricity as the etiology of local recurrence. Five patients (83.3%) with local recurrence were alive and asymptomatic at a mean of 138 months after partial nephrectomy. Since capsular penetration was identified in 5 of 27 renal cell carcinomas (18.5%) with a diameter of 3.5 cm. or less, aggressive surgical resection with adequate tumor-free parenchymal and perinephric margins is necessary even for small lesions. CONCLUSIONS: With improved surgical techniques, including regional hypothermia, intraoperative sonography, meticulous dissection and injection of the collecting system with methylene blue, partial nephrectomy is safe and effective in properly selected patients.

Adolescent↗

Correlation of clinicopathologic features of resected hepatocellular carcinoma with hepatitis C virus genotype.

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.

Aged↗

[Recurrent carcinoma in situ of the uterine cervix (author's transl)].

Among 228 patients who had previous treatment for carcinoma in situ of the cervix, most by hysterectomy, 3 recurrences in vaginal stumps were detected in women age 36, 46, and 56. In another case a carcinoma in situ of the cervix was found in a 25 year old patient who had a diagnostic and therapeutic conization because of desire for childbearing. The histology of the cone showed no residual carcinoma. Concommitent to the recurrent carcinoma in situ of the cervix a carcinoma of the vulva was detected. Recurrences of carcinoma in situ could occur because of incomplete resection of primary lesion. Wrong classification in the laboratory is possible if the invasion is missed on the microscopic examination and the case therefore receives the wrong treatment. Recurrences which are not true recurrences could arise from multicentric atypical foci of the squamous epitheleum of the -ower female genital tract. These considerations lead to the following recommendations: 1. When the suspected diagnosis carcinoma in situ of the uterine cervix is made a large enough cone biopsy which is appropriately marked is obtained and a complete microscopic examination of the cone must be obtained. 2. A hysterectomy with a large vaginal cuff is the treatment of choice. 3. A careful workup of the operative specimen in the microscopic laboratory is expecially essential. 4. A patient with such previous treatment for carcinoma in situ of the uterine cervix must be urged to continue with regular preventive examinations for cancer. The vaginal stump must be regularly re-examined both by colposcopy and by cytology.

Adult↗

Transitional cell carcinoma of the clitoris: direct implantation or metastasis.

Transitional cell carcinoma (TCC) of the bladder is the seventh most frequent cancer of women. The possible mechanisms of local tumor recurrence are seeding and multicentricity. Distant metastases are most frequently as a result of vascular or lymphatic spread and to a lesser extent by seeding of the tumor cells with urine or transurethral instrumentation. We report a clitoral metastasis of a TCC of the bladder, which is a very unexpected and extremely rare site for metatstasis and discuss whether the possible mechanism is vascular spreading or direct seeding. To our knowledge this is the third case in the literature.

Aged↗

Inflammatory myofibroblastic tumor in children: clinical review with anaplastic lymphoma kinase, Epstein-Barr virus, and human herpesvirus 8 detection analysis.

BACKGROUND/PURPOSE: Inflammatory myofibroblastic tumor (IMT) is considered as an intermediate neoplasm that may present malignant features. Differential diagnosis with other tumor processes is sometimes difficult. Similar anaplastic lymphoma kinase (ALK) gene abnormalities as in anaplastic large cell lymphoma have been reported. Human herpesvirus 8 (HHV-8) DNA sequences have been described in adult pulmonary IMTs and Epstein-Barr virus (EBV) has been reported in splenic and hepatic IMTs, suggesting the importance of both viruses in IMT development. This article aims to evaluate ALK, EBV, and HHV-8 expression in children with IMT and to correlate our findings with clinical features. METHODS: Sixteen children (range, 1-15 years) who had surgery for IMT between 1978 and 2003 were evaluated retrospectively. Formalin-fixed, paraffin-embedded archival tissues were stained for HHV-8 and ALK with immunohistochemistry. Epstein-Barr virus was detected by in situ hybridization (EBER probes). RESULTS: Tumors were located in the pulmonary lobe (n = 4), urinary tract (n = 4), mesentery or bowel (n = 4), hepatic lobe (n = 1), vena cava (n = 1), spinal cord (n = 1), and soft tissue (n = 1). Five children were treated with steroids and/or antibiotics before surgery, with no substantial result. IMT was excised totally in all but 2 cases. Four patients presented aggressive IMT with recurrence or metastasis requiring new surgery. ALK was positive in 3 (18.8%) cases and EBV in 1 pulmonary and 1 bladder tumor, all of them without recurrence or metastasis. None of the cases were positive for HHV-8. All patients are now disease-free with a mean follow-up of 4.2 years. CONCLUSIONS: Considering the present lack of efficient medical treatment, surgery should still be considered as the mainstay therapy in IMT, even in cases of recurrence or metastases. Larger multicentric studies would be necessary to understand the prognostic significance of ALK, EBV, and HHV-8 and their relationships with the origins of the tumor.

Adolescent↗

Clinicopathologic risk factors for recurrence after a curative hepatic resection for hepatocellular carcinoma.

BACKGROUND: The long-term prognosis after resection for patients with hepatocellular carcinoma is still unsatisfactory because of the high recurrence rate. The survival of patients with multiple intrahepatic or extrahepatic recurrence is especially poor. METHODS: Among the patients who underwent hepatic resection for hepatocellular carcinoma between 1981 and 2000, 216 patients with 3 or less than 3 intrahepatic recurrences (group B); 156 patients with more than 3 intrahepatic recurrences, extrahepatic recurrences, or both (group C); and 51 patients who survived more than 5 years without recurrence (group A) were clinicopathologically studied. RESULTS: The period to recurrence of group C was significantly earlier than that of group B and also showed a significantly poor prognosis after recurrence. Tumor factors, including size, portal venous invasion, intrahepatic metastasis, histologic grade, or the number of tumors at resection in group C was significantly worse than in groups A and B. Although no differences are recognized in the tumor factors between groups A and B, except for the alpha-fetoprotein level, liver function in group B was significantly worse than that in group A. In addition, the frequency of hepatitis B surface antigen in group B and that of hepatitis C virus in group B was significantly less and higher than that in group A, respectively. CONCLUSION: Similar to extrahepatic metastasis, multinodular recurrences are also mainly caused by metastatic recurrence from the main tumor by means of the portal system, and recurrences with up to 3 intrahepatic nodules are mainly caused by metachronous multicentric hepatocarcinogenesis. Because the mechanisms of recurrence differed, determining the patterns of recurrence on the basis of the clinicopathologic findings is important for selecting the optimal postoperative therapy for each individual patient.

Alanine Transaminase↗

Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation.

The clinicopathologic features of 24 tumors showing perivascular myoid differentiation are described. These included tumors with histologic features of "infantile-type" myofibromatosis occurring in adult patients (8 cases), tumors with composite features of "hemangiopericytoma" and glomus tumor (9 cases), and tumors with a distinctive concentric perivascular proliferation of spindle cells (7 cases). Evidence of morphologic overlap among these groups suggests they are closely related neoplasms that form a single spectrum. Age of patients with lesions resembling infantile-type myofibromatosis ranged from 23 to 67 years (median, 37 years). Clinicopathologic manifestations of this disease included multicentricity (4 cases), local recurrence (3 cases), persistence of congenital lesions into adulthood (4 cases), and tumors that were multifocal within the confines of one anatomic region (7 cases). Histologically, all cases showed a biphasic pattern that consisted of fascicles of spindle cells with abundant eosinophilic cytoplasm that resembled smooth muscle, in addition to a population of more primitive spindled cells associated with a hemangiopericytomalike vascular pattern. Six cases showed reversal of the typical zonation seen in pediatric cases in that the primitive component surrounded the more mature fascicular areas. Also described are nine tumors with features that are intermediate between glomus tumor and hemangiopericytoma, which we have designated glomangiopericytoma. These tumors are characterized by prominent branching vessels lined by a single row of endothelial cells surrounded by epithelioid cells with a glomoid appearance. In other areas, the tumors showed typical hemangiopericytomatous foci similar to those in the myofibromatosis cases. The principal points of distinction were a lack of myoid nodules and an absence of small primitive cells with basophilic cytoplasm. Ages of these patients ranged from 17 to 78 years (median, 35 years). All tumors were located in the subcutaneous tissue and the superficial soft tissue of the extremities. Recurrence developed in one of six patients with follow-up information. The recurrent tumor had features of angiomatoid malignant fibrous histiocytoma. Finally, we describe a subset of tumors characterized by concentric periluminal proliferation of bland, round to ovoid cells, which we have designated as myopericytoma. Patient age ranged from 10 to 66 years (median, 40 years). All were located in subcutaneous and superficial soft tissue of distal extremities. One patient had two recurrences in 3 years after initial excision. Our study suggests that these three lesional groups comprise a histologic continuum of tumors that share clinical similarities and that, perhaps, are designated more appropriately as perivascular myomas. The relationship of this family of tumors to so-called hemangiopericytoma is discussed.

Actins↗

The nipple-sparing mastectomy: early results of a feasibility study of a new application of perioperative radiotherapy (ELIOT) in the treatment of breast cancer when mastectomy is indicated.

BACKGROUND: Breast cancer surgery has become less and less mutilating, however a mastectomy is required in the case of multicentric, large tumors or recurrences after conservative treatment. The removal of the nipple areola complex during the mastectomy dramatically increases the feeling of mutilation. To reduce this negative psychological impact, in cancers located outside of the central area of the breast, we propose a new type of nipple-sparing mastectomy associated with intraoperative electron beam radiotherapy (ELIOT) delivered on the region of the areola. The nipple-sparing mastectomy is performed leaving 5 mm of glandular tissue behind the nipple areola complex to preserve its blood supply. The reconstruction is immediately performed with a prosthesis or an autologous flap. PATIENTS AND METHODS: Twenty-five patients were included in the study; two of them had a bilateral nipple-sparing mastectomy. RESULTS: Pathological examinations demonstrated the presence of 19 infiltrating carcinomas and 8 ductal carcinoma in situ. Two patients had a superficial skin areolar slough followed by spontaneous healing. One necrosis of the areola occurred due to extensive retroareolar dissection. In the early follow-up, the color of the areola was preserved. All patients except one expressed their satisfaction of having kept their areola. CONCLUSIONS: These preliminary results are encouraging but they require further studies to evaluate the long-term results, the local recurrence rate and the psychological impact.

Adult↗

Primary malignant melanoma of the esophagus.

Three cases of primary malignant melanoma of the oesophagus are presented and the literature is briefly reviewed. This rare disease affects predominantly males in the sixth decade of life or later and the clinical and radiologic features are indistinguishable from those of more common oesophageal carcinomas. The tumours are often polypoid, located mainly in the lower two-thirds of the esophagus, and their histologic features resemble those of lentigo maligna melanoma, but with more aggressive biologic behavior. Because of the potential for extensive intramucosal involvement, multicentricity and high local recurrence rate, surgical treatment requires radical excision with a much greater margin than for the common squamous cell carcinomas. Though the outlook is poor, surgery is the favoured treatment with palliative or curative intent, with a 5-year survival rate of 4.2%. Radiotherapy, chemotherapy and immunostimulation currently serve mainly as palliative or adjunctive measures.

Adult↗

[Role of 99mTC-Sestamibi in the diagnosis of breast cancer. Report on 100 cases].

OBJECTIVE: To evaluate the usefulness of the isotopic mammography with 99mTc-MIBI in the diagnosis of tumoral pathology of the mammary gland. METHODS: One hundred women with clinical/radiological suspicion of malignant pathology in the breast and/or lymph nodes were studied. The isotopic technique consisted of administration 740MBq 99mTc-MIBI, i.v., obtaining AP and prone lateral views. RESULTS: The overall sensitivity and specificity for the scintimammography in tumoral detection was 90% and 86% respectively. The sensitivity was 60% in nonpalpable lesions. The scintimammography had a 40% sensitivity and 98% specificity in lymph node detection. CONCLUSION: The complementary use of scintimammography can improve the sensitivity for the detection of breast carcinoma. The diagnostic accuracy of 99mTc-MIBI depends on the tumor size and histopathological characteristics. The 99mTc-MIBI can potentially determine the presence of recurrent breast cancer and multicentric disease.

Adult↗

[Gastrojejunostomy versus endoscopic stent placement as palliative treatment for a malignant constriction of the duodenum: the SUSTENT-study].

Gastric-outlet obstruction often results from inoperable distal stomach, periampullary (pancreatic or cholangio-), or duodenal carcinoma. Gastrojejunostomy and stent placement are standard palliative treatments. An advantage of gastrojejunostomy is the long-term efficacy; a disadvantage is the prolonged postoperative recovery time. The advantage of stent placement is the rapid ability to consume a soft diet; a disadvantage is that around 20% of the patients require re-intervention because of recurrent symptoms. A randomised multicentre study was started in January 2006 in the Netherlands in which gastrojejunostomy is compared with stent placement in the palliative treatment of malignant gastroduodenal obstruction: 'Surgery versus stent for malignant gastroduodenal obstruction', the SUSTENT-study. The primary-outcome measurement is survival adjusted for the time patients are not able to consume (soft) food. Other outcome measurements are medical effects (complications, re-interventions), quality of life, cost and cost-effectiveness. This study aims to provide individualised recommendations for effective palliative treatment of patients with malignant gastroduodenal obstruction.

Digestive System Neoplasms↗

Fibroadenomas with stromal cellularity. A clinicopathologic study of 21 patients.

Data on clinical and pathologic features of tumors from 21 patients who had breast tumors compatible with juvenile (cellular) fibroadenomas (JCF) were reviewed. All patients were black females ranging in age at time of presentation from 10 to 39 years, with a median age of 15 years. Follow-up (median period, six years) was obtained for 20 patients. Patients were categorized into two groups; 13 had solitary lesions and eight had multiple and successive lesions. No histologic differences were observed between JCF occurring as solitary or multiple tumors or between lesions occurring in patients younger and older than age 20 years. The JCF was shown to be a fairly distinct clinicopathologic entity that characteristically occurred in adolescents, but which was occasionally seen in young adults. It had a benign course, characterized by synchronous and metachronous multicentricity, rather than local recurrence.

Adenofibroma↗