Foci Of Vascular Invasion Research Articles

Remodeling of Mineralized Tissues, Part II: Control and Pathophysiology

Based on a review of literature, the bone remodeling concepts, as defined by Harold Frost, are extended to the molecular level to help explain common bone physiopathology. Remodeling of mineralized tissue is an inflammatory response to accumulated tissue damage. Inflammation activates (A) the localized cell population, which attracts circulating osteoclast precursors, and initiates foci of vascular invasion. Coordination of these cybernetic events results in formation of a cutting/filling cone (cortical bone) or a hemicutting/filling cone (trabecular bone). Damaged bone is resorbed (R) creating a self-limited resorption cavity that is then filled by bone formation (F). A genetic mechanism (RANK/RANKL/OPG) is proposed for coupling bone formation to resorption during the remodeling process. Following surgery and/or initiation of orthodontic tooth movement, a regional acceleratory response (RAP) occurs throughout the affected alveolar process. Undermining resorption during the initial stage of tooth movement is analogous to initiation of a bone remodeling cycle (A→R→F). Understanding the cell dynamics of the ARF sequence is fundamental for appreciating common remodeling disorders such as osteoporosis, Paget's disease, hypo- and hyperparathyroidism, metastases, and external apical root resorption. Depending on the physiopathologic context, remodeling may enhance or limit the orthodontic options for management of a malocclusion.

Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland

Follicular carcinomas of the thyroid gland, including its oncocytic variant (so-called Hurthle cell carcinoma), are subdivided into the indolent encapsulated ("minimally invasive") and the clinically aggressive widely invasive tumors. There are, however, cases of encapsulated follicular carcinoma that recur and metastasize. Identifying these cases at the time of diagnosis is crucial for prognostic and therapeutic considerations. Because to the authors' knowledge most studies do not focus exclusively on the encapsulated Hurthle cell carcinoma (EHC), the current study attempted to identify predictors of recurrence in EHC. A tumor was defined as EHC if it was encapsulated, macroscopically well defined with microscopic but no macroscopic evidence of vascular or capsular invasion, and composed of > 75% follicular oncocytic cells. Retrospective chart review and microscopic examination identified 50 primary tumors meeting the above criteria at the Memorial Sloan-Kettering Cancer Center between 1967 and 2005. The cases were analyzed for various histologic and clinical parameters. Each parameter was correlated with recurrence-free survival (RFS). Seven of 50 (14%) patients developed disease recurrence. All patients who developed recurrence were found to have a high number of foci of vascular invasion (> or = 4). In univariate analysis, > or = 4 foci of vascular invasion (P <.0001), tumor size > 4 cm (P = .049), the presence of mitosis (P = .018), and a solid/trabecular growth pattern (P = .009) were found to be correlated with a decreased RFS. Extensive capsular invasion, gender, and age did not confer a statistically higher recurrence rate. The finding of a solid/trabecular growth and mitosis correlated with the presence of numerous foci (> or = 4) of vascular invasion (P = .01 and P = .005, respectively). A diligent search for vascular invasion is recommended in EHC that display mitosis or a solid/trabecular growth pattern. The presence of > or = 4 foci of vascular invasion should alert the pathologist and the clinician to a significantly higher risk of recurrence in EHC.

Proximal-Type Epithelioid Sarcoma: Report of Two Cases in the Perineum

The authors report two cases of perineal proximal-type epithelioid sarcoma in middle-aged men, age 51 and 43 years old. Both tumors were located in the right side. In the first patient a 7.5-cm, well-encapsulated tumor was completely excised. The second patient was a referral case with incomplete excision, but the computed tomography scan and magnetic resonance imaging showed a 14-cm nonencapsulated tumor involving the soft tissues of the inner thigh and perineum, as well as metastasis in right inguinal and retroperitoneal lymph nodes. Both neoplasms had a predominant solid pattern alternating with occasional discohesive areas. Both were composed of large oval to polygonal cells with vesicular nuclei, conspicuous nucleoli, and amphophilic to eosinophilic cytoplasm. Rhabdoid phenotype was identified in the second case only. The first neoplasm displayed 15% necrosis, 7 mitoses per 10 high-power field, focal vascular invasion, and no extracapsular invasion. The other exhibited 60% necrosis, 12 mitoses per 10 high-power fields, extensive vascular invasion, no distinct capsule, and invasion of the surrounding fatty tissue. Both were positive for vimentin, cytokeratin, epithelial membrane antigen, and CD34. Muscle-specific actin was negative in the first case and focally positive in the second. CD56 was positive in the second case and negative in the first case. Desmin, CD45, CD30, factor VIII, CD31, S100, HMB45, calretinin, and synaptophysin were negative in both. Since proximal-type epithelioid sarcoma can be confused with a number of other soft tissue tumors with epithelioid and/or rhabdoid features, the authors emphasize the immunohistochemical differential diagnosis.

Vascular invasion predicts recurrence after radical prostatectomy: Stratification of risk based on pathologic variables

Objectives To determine whether vascular invasion (VI) is an independent predictor of prostate cancer recurrence and/or survival and to stratify risk of recurrence in patients with VI. Methods Vascular invasion status was documented in 620 radical prostatectomy specimens with an average of 7.5 years of follow-up. The relationship between VI and other clinical and pathologic features was tested. Vascular invasion as an independent predictor of recurrence was investigated by logistic regression analysis. Survival analyses and stratification of VI patients was developed with Kaplan-Meier survival curves. Results Vascular invasion was identified in 110 patients (18%) and correlated significantly ( P <0.0001) with high Gleason grade, extracapsular extension (EPE), seminal vesicle invasion, increasing cancer volumes, positive margins, and elevated preoperative prostate-specific antigen (PSA) levels. Logistic regression analysis demonstrated that VI was a strong and independent predictor for disease recurrence, when considered with grade, EPE, seminal vesicle invasion, lymph node involvement, cancer volume, preoperative PSA levels, and positive margins. At 12 years after radical prostatectomy, patients with VI demonstrated significantly lower disease-specific survival ( P = 0.0005). Among patients with VI, stratification of grade, EPE, and the number of VI foci identified three significantly different prognostic groups. Conclusions In long-term follow-up, VI was a significant predictor of prostate cancer recurrence and death after radical prostatectomy. In patients with VI, high Gleason grade, EPE, and more than five foci of VI are associated with poor prognosis.

PROSTATE CANCER IS HIGHLY PREDICTABLE: A PROGNOSTIC EQUATION BASED ON ALL MORPHOLOGICAL VARIABLES IN RADICAL PROSTATECTOMY SPECIMENS

We determine whether biochemical prostate specific antigen (PSA) failure can be accurately predicted from preoperative serum PSA combined with 6 morphological variables from radical retropubic prostatectomy specimens in men with peripheral zone cancers. The unexpected limitation imposed by preoperative serum PSA on biochemical failure led us to compare peripheral zone to transition zone cancers. A total of 326 peripheral zone and 46 transition zone cancers treated only with radical retropubic prostatectomy were followed for a minimum of 3 years (mean and median greater than 5). All prostates were sectioned at 3 mm. intervals and morphological variables were quantitated using the Stanford technique. Biochemical failure was defined as serum PSA 0.07 ng./ml. or greater and increasing. Multivariate logistic regression was used to identify variables with the most independent influence on biochemical failure and derive a clinical equation to predict failure in peripheral zone cancers. The validity of the predictive equation was assessed by out of sample validation and cross validation techniques. The 46 transition zone cancers were compared to the 326 peripheral zone cancers by Student's t and Wilcoxon tests. Of the peripheral zone failures 60% occurred in the first year after radical retropubic prostatectomy and 95% had occurred by the end of year 4. The highest preoperative serum PSA was 23 ng./ml. among the 181 men biochemically free of disease. Only 15.8% of 57 men with PSA greater than 15 ng./ml. were biochemically disease-free. For the 48 transition zone cancers cure rates were independent of serum PSA with 6 men having PSA greater than 50 ng./ml. Biochemical disease-free status was noted in 80% of transition zone compared to 56% of peripheral zone cancers (p = 0.0009). The most important variables predicting biochemical disease-free status for peripheral zone cancers were percent Gleason grade 4/5, cancer volume, serum PSA and prostate weight. Foci of vascular invasion, intraductal cancer and lymph nodes were less significant variables, and capsular penetration, positive surgical margins and seminal vesical invasion were insignificant. The multivariate logistic equation for predicting failure in peripheral zone cancers was highly accurate and requires only 2 to 3 minutes with a simple calculator. Failure of radical retropubic prostatectomy to cure peripheral zone prostate cancer is highly predictable based on 6 morphological variables from the prostatectomy specimen and serum PSA. The level of serum PSA profoundly limits biochemical cure rates in peripheral zone cancers. Transition zone cancers have a high cure rate, despite high serum PSA and adverse morphological variables. Men with serum PSA greater than 15 and perhaps even greater than 10 ng./ml. have such a low cure rate for peripheral zone cancer that re-biopsy attempts appear indicated to prove a transition zone location or else therapy other than radical retropubic prostatectomy should be sought. Pathologists should indicate whether the primary (largest) cancer is in the peripheral or transition zone to prevent overoptimistic reports of cure with radical prostatectomy procedures, as 85% of all tumors are in the peripheral zone.

Metastatic Minimally Invasive (Encapsulated) Follicular and Hurthle Cell Thyroid Carcinoma: A Study of 34 Patients

Most studies that have examined minimally invasive, encapsulated, follicular carcinoma (FC) or Hurthle cell carcinomas (HCs) have contained only a few metastatic neoplasms. We studied 34 patients with a single, minimally invasive, metastatic FC or HC and compared them with 38 patients with similar, nonmetastatic FCs or HCs. The numbers of incomplete capsular penetration (neoplasm into but not through the capsule), complete capsular penetration (neoplasm through the capsule), and vascular invasion foci were quantified. The median number (three), range, and distribution of complete capsular penetration and vascular invasion foci were similar in the nonmetastatic and metastatic carcinomas. All of the metastatic FCs and HCs had at least one vascular invasion or complete capsular penetration focus. Sixty-two percent of the metastatic carcinomas had two to four complete capsular penetration foci, and 60% had two to four vascular invasion foci. Two metastatic neoplasms had incomplete capsular penetration but had one and two vascular invasion foci, respectively. One tumor had no vascular invasion but had four complete capsular penetration foci. No metastatic neoplasms had incomplete capsular penetration only. There were no differences in the number of vascular invasion or complete capsular penetration foci between metastatic and nonmetastatic FCs and HCs and between metastatic FCs and HCs. Most metastatic neoplasms had vascular space invasion and complete capsular penetration. The number of complete capsular penetration or vascular invasion foci was not associated with the initial site of metastasis or the interval between the surgery and the metastasis.

Significance of demonstrable vascular space invasion for the progression of prostatic adenocarcinoma.

Histologically demonstrable vascular invasion by tumor has been reported as an index of poor prognosis correlating with increased probability of metastasis in many types of cancer other than prostatic. We quantitated vascular invasion foci in 357 radical prostatectomy specimens and developed improved criteria for their diagnosis and their distinction from fixation artifact. Vascular invasion foci were found in 7% of cancers less than 4 cc in volume and 24% of larger cancers. Most foci were selectively located either near the basal end of the cancer or near the transition zone border. Correlations among multiple morphologic variables showed significant correlation of vascular invasion only with the presence of intraductal carcinoma. The only statistically significant independent predictors of disease progression (serum prostate-specific antigen elevation) were vascular invasion, carcinoma grade, and cancer volume. Our findings suggest that further study of vascular invasion foci may disclose additional information about the biologic features of local and distant spread of prostatic carcinoma.

Aromatase expression in a feminizing adrenocortical tumor

A 29-yr-old man was referred for evaluation of progressive bilateral gynecomastia, diminished libido, and impotence. There was no history of exposure to exogenous estrogen, androgen antagonists, or alcohol. Physical examination revealed symmetric gynecomastia (5 X 5 cm), a feminized body contour, and diminished testicular size (9 and 8 mL, respectively). Blood pressure was 130/85 mm Hg. Liver and thyroid functions were normal. The sperm count showed azoospermia. A computerized axial tomographic scan of the abdomen revealed a left adrenal mass (9 X 9 X 10 cm). The diagnosis was made based upon high plasma estrone (E,) and estradiol (EJ levels. After detailed endocrine preoperative testing and catheterization of adrenal veins, the patient underwent left adrenalectomy. An adrenal cortical carcinoma was removed without complications. The weight of the encapsulated adrenal mass was 210 g. Severe nuclear pleomorphism was present, with frequent mitoses and multiple foci of vascular invasion. After resection of the tumor, plasma E, and E, levels fell dramatically. Three months later, gynecomastia had regressed, and the patient had normal sexual intercourse. Four years after surgery, whereas E, and E, remained in the normal range, a chest computed tomography scan detected a lung nodule. Resection and histological analysis of this nodule confirmed the existence of a distant metastasis, and mitotane therapy was started.

Occurrence and significance of vascular invasion in multinodular adenomatous goiter.

Solitary follicular neoplasms of the thyroid gland are usually classified as adenomas or carcinomas according to two main criteria: vascular invasion and capsular penetration. No information is available on the occurrence of vascular invasion in multinodular goiter lesions, except for the case of a follicular carcinoma within a goiter. One thousand consecutive cases of multinodular adenomatous goiter were reviewed. After screening all H&E-stained slides, 5 patients with histological features typical of adenomatous goiter but displaying foci of vascular invasion at the periphery of the nodes were selected. A single vessel (2 patients) and 2-4 vessels (3 patients) at the periphery of different nodules were involved, with clusters of follicular cells lined by endothelium and partly filling the lumen. Clinical information was obtained from all patients: No recurrences or progressive disease were reported 14 to 16 years after operation. These findings indicate that presence of minimal vascular invasion, although a valuable criterion of differentiation in solitary follicular lesions of the thyroid, has little diagnostic importance in the setting of multinodular adenomatous goiter. It does not appear to justify a diagnosis of malignancy and does not indicate a need for further therapy.