Muscle differentiation and clinicopathologic features of gastrointestinal stromal tumors

We analyzed 46 gastrointestinal stromal tumors (GISTs) using a panel of antibodies to determine the frequency of smooth muscle differentiation and the relationship of immunophenotype to histopathologic features and clinical behavior. Thirty-six GISTs were classified as benign or malignant based exclusively on clinical behavior; a 2-year minimum follow-up was required for benign lesions. GISTs were immunopositive in the following categories: vimentin 45 of 46, desmin nine of 45, muscle-specific actin (MSA) 36 of 46, alpha-smooth muscle actin (SMA) 34 of 46, chicken gizzard actin-7 zero of 38, cytokeratin two of 46, S100 protein six of 46, glial fibrillary acidic protein (GFAP) zero of 46, synaptophysin zero of 46, and chromogranin one of 46. At least one muscle marker was positive in 39 of 46 tumors. Five GISTs were MSA positive/SMA negative, and three were MSA negative/SMA positive. All desmin-positive cases reacted with MSA or SMA. Eight GISTs were positive for vimentin, MSA, SMA, and desmin, whereas seven were vimentin positive only. Compared with the latter, the former tended to be smaller, less often necrotic, and clinically benign (p less than 0.05 for each). All vimentin-positive only GISTs were malignant. Immunohistochemical features did not correlate with tumor site, cellularity, nuclear pleomorphism, or mitotic rate. Benign GISTs were less cellular than were malignant GISTs (p less than 0.05), but they did not differ statistically in degree of nuclear pleomorphism, necrosis, mitotic rate, or size. We conclude that (a) 85% of GISTs react with at least one muscle antibody; (b) immunohistochemical features are unrelated to anatomic site; (c) SMA is, in effect, as sensitive as MSA, whereas desmin is less sensitive; and (d) simultaneous vimentin, MSA, SMA, and desmin positivity correlates with a benign outcome.     

A comparative study on morphology and immunohistochemistry of rhabdomyosarcoma and embryonal skeletal muscles

OBJECTIVE: To investigate the histologic and histogenetic relationship between various types of rhabdomyosarcomas (RMS) and embryonal skeletal muscle (ESM) for further understanding of the histogenesis, classification and pattern of differentiation of RMS. METHODS: Fifty cases of variant types of RMS and 20 cases of ESM at different gestational ages were available. All specimens were stained with HE, PAS, Van Gieson, Masson, phosphotungstic acid hematoxilin and with antibodies for the demonstration of vimentin, desmin, HHF-35 and myoglobin by ABC method. RESULTS: The results showed that the order of positive expression and the intensity of positive reaction of the different immunohistochemical staining were consistent with the degree of differentiation of the tumor and the development of the ESM. It is obvious that each type of RMS is composed of tumor cells in different degree of differentiation and is derived from primitive mesodermal cells which are capable of potential differentiation towards mature skeletal muscles. CONCLUSIONS: Based on the results of this study, an ideal histologic classification of RMS should reflect not only the cell morphology and histologic structures but also the degree of differentiation of the tumor cells.     

Adenosarcoma of the uterine cervix presenting as a cervical polyp

A case of adenosarcoma arising from the uterine cervix of a 55-year-old female who complained of vaginal discharge is reported. A polyp, 6 x 2 x 1.5 cm in size, identified in the cervical canal was clinically diagnosed as benign cervical polyp and resected. Histologically, the polyp was composed of benign epithelial components and sarcomatous stroma wherein periglandular hypercellularity and some mitoses including atypical ones were noted. Immunohistochemically, stromal cells were positive for muscle-type actins, desmin and estrogen receptor. Adenosarcoma is a rare, biphasic tumor of the uterus and usually presents as a polypoid mass in the endometrial cavity. When they arise from the cervix, adenosarcomas may be confused with benign cervical polyps clinically and pathologically. As the former often recurs, microscopic differentiation is crucial for further treatment.     

Long-term survivors with pN2 non-small cell lung cancer after a complete resection with a systematic mediastinal node dissection

OBJECTIVE: To determine the distribution and significance of microcalcifications in histologic sections of the prostate. DESIGN: Retrospective review of all histologic slides of completely embedded prostates from surgical specimens. MATERIALS: Randomly selected material included 266 radical prostatectomy and 10 cystoprostatectomy prostates without prostate cancer. Nonrandomly selected specimens included 26 radical prostatectomy specimens with a Gleason pattern 5 component, 24 cases with collagenous micronodules, and 8 cases previously noted to have microcalcifications within foci of prostate cancer. RESULTS: Four patterns of microcalcifications were noted in association with prostate cancer: (1) dystrophic calcification in the comedo-type necrosis of Gleason pattern 5, (2) intraluminal calcification in cribriform-type Gleason pattern 3 prostate cancer, (3) intraluminal calcification in small acinar adenocarcinoma, and (4) stromal calcification within collagenous micronodules associated with prostate cancer. Microcalcifications were noted in 32% of prostates without cancer; 1.9% of randomly selected prostates demonstrated microcalcifications associated with prostate cancer. CONCLUSIONS: Microcalcifications are less common in association with prostate cancer than with benign prostatic ducts and acini. However, intraluminal microcalcifications associated with an atypical small glandular proliferation should not be taken as unequivocal evidence of a benign process.     

Bronchoalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically treated patients

BACKGROUND: Liposarcoma arising within a phyllodes tumor is extremely rare. To the best of our knowledge, a malignant phyllodes tumor with liposarcomatous stroma diagnosed by fine needle aspiration (FNA) has not been reported before. CASE: A 39-year-old female had a malignant phyllodes tumor with liposarcomatous stroma diagnosed by FNA cytology. Two subtypes of liposarcomatous stroma, including lipomalike differentiated and myxoid, were found in the aspirates. The cytologic findings were very representative of the histologic features. CONCLUSION: It is very important to recognize the cytologic features of such rare tumors. An accurate diagnosis preoperatively by FNA permits better therapy planning.     

Adenomas of the rete ovarii

This article reports the clinicopathological and immunohistochemical findings of two cases of adenoma of the the rete ovarii (RO), one unilateral and the other bilateral, presenting with atypical histological features in the right ovary. Both tumors were incidental findings in 62- and 64-year-old patients presenting with metrorrhagia. The predominantly cystic lesions measured 2 cm and 3 cm in diameter and microscopically, they were tubulopapillary proliferations of regular columnar cells with clear cytoplasm. The stroma showed extensive differentiation of polygonal, Leydig-like cells which was associated in both cases with simple endometrial hyperplasia. In both cases rete and hilar mesonephric remnants were found in the vicinity of the lesion. The atypical lesion in one case had a complex papillary proliferation different in pattern and cellularity from a retiform Sertoli-Leydig cell tumor. It showed extensive areas of eosinophilic change, pleomorphism, and a few mitoses but did not invade the adjacent ovarian stroma. Its stroma also had steroidally active cells. The patient was alive and well after a follow-up interval of 3 years. Immunohistochemically, the lesions were diffusely positive for CAM 5.2, vimentin, epithelial membrane antigen, OC 125, OC 125, and progesterone receptors.     

Stromal tumors of the jejunum and ileum: a clinicopathologic study of 39 cases

Recently, cell size, cell density, and growth pattern were found to be reliable histologic parameters in separating benign from malignant duodenal stromal tumors. However, there are few data on the histologic features and important prognostic parameters of stromal tumors from other parts of the small bowel. Thus, we studied the clinical and pathologic features of 39 stromal tumors of the jejunum and ileum to determine which parameters would be most useful in distinguishing a benign from a malignant tumor. In all cases, the following histologic parameters were recorded: (a) predominant growth pattern (organoid, fascicular, solid, or mixed), (b) cellularity (low or high), (c) predominant cell type (spindled, epithelioid, or mixed), (d) nuclear pleomorphism (minimal, moderate, or severe), (e) the presence or absence of tumor cell necrosis, (f) the presence or absence of mucosal infiltration, (g) the presence or absence of skeinoid fibers, and (h) the number of mitotic figures per 50 high-power microscopic fields (HPF). Clinical follow-up was obtained in all cases, and the patients were considered to have suffered an adverse outcome if they developed metastatic disease or died as a complication of their tumor. In the absence of these features, patients were not considered to have suffered an adverse outcome. Twenty-five patients suffered an adverse outcome. Twenty-one patients died of disease from 1 month to 9 years (median: 2 years). One patient died at 4 days because of postoperative complications. Three patients were alive with metastatic disease at 6 months, 6 years, and 7 years. Twenty-four of these 25 patients developed metastatic disease, most commonly to the liver. Fourteen patients did not suffer an adverse outcome. Eleven patients were alive without disease from 2 to 11 years (median: 3 years), and three patients died of unrelated causes at 1, 1, and 3 years. Although there was some overlap in features between clinically benign and malignant tumors, features that were significantly associated with an adverse outcome included tumor size > 5 cm, mitotic counts > 5 mitotic figures per 50 HPF, high cellularity, the absence of a predominant organoid growth pattern, the absence of skeinoid fibers, the presence of severe nuclear pleomorphism, and the presence of mucosal infiltration and tumor cell necrosis (p < 0.05 using the chi-square and Fisher's exact tests). Features that were significantly associated with decreased survival included tumor size > 5 cm, mitotic counts > 5 mitotic figures per 50 HPF, high cellularity, the absence of skeinoid fibers, and the presence of tumor cell necrosis (p < 0.05 using the Mantel-Haenszel log-rank test). Given the fact that there is some overlap in these features between clinically benign and malignant tumors, a multiparametric analysis using the above features is the most effective way of predicting clinical behavior.     

Immunohistochemical detection of sialosyl-Tn antigen in carcinoma of the prostate

OBJECTIVE: To investigate the expression of sialosyl-Tn antigen (STn) in human benign and malignant prostate. MATERIALS AND METHODS: The expression of STn was investigated immunohistochemically in formalin-fixed and paraffin-embedded tissue specimens from 56 patients with primary prostatic adenocarcinoma (median age 74.3 years, range 47-89) and 20 patients with benign prostatic hyperplasia (median age 73.4 years, range 60-87). RESULTS: STn was expressed in only three (4%) of the 20 hyperplastic glands and the benign areas adjacent to the 54 carcinomas; by contrast, STn was expressed in 34 (61%) of the 56 carcinomas. The frequency of STn positivity was much higher in well-differentiated carcinomas than in those poorly differentiated. CONCLUSION: STn is expressed with malignant transformation of the prostatic epithelial cells and immunohistochemical methods using commercially available STn monoclonal antibody may be useful as an adjunct for distinguishing carcinoma from benign tissue.     

Solitary fibrous tumor of soft tissue: a report of 15 cases, including 5 malignant examples with light microscopic, immunohistochemical, and ultrastructural data

We describe 15 soft tissue solitary fibrous tumors (SFTs) occurring in patients 24 to 78 years old (average, 50.6 yr). Ten tumors were benign and arose in the head and neck area (three tumors), thigh (two), vulva (two), upper arm (one), lower leg (one), and retroperitoneum (one). Five tumors were histologically malignant and arose in the thigh (two), abdominal wall (one), buttock (one), and retroperitoneum (one). All of the tumors were grossly well circumscribed. The benign tumors measured from 2 to 10 cm (average, 4.8 cm) and the malignant ones from 3 to 5.5 cm (average, 4.3 cm) in greatest diameter. Microscopically, the benign tumors showed areas of hypercellularity with variable amounts of collagenous and myxoid stroma; one had amianthoid fibers. The malignant tumors were composed of cytologically atypical cells enmeshed in a collagenous or myxoid extracellular matrix. Ultrastructural study of three benign and three malignant tumors showed fibroblastic differentiation; one benign tumor showed myofibroblastic differentiation. Immunohistochemically, all of the tumors examined were immunoreactive for vimentin, and seven of nine were positive for CD34, including all of the malignant ones. There was focal staining for muscle actin in two benign tumors and for Leu-7 in one benign tumor; there was no staining for cytokeratin, desmin, S-100 protein, epithelial membrane antigen, or smooth muscle actin in any of the examined tissues. Follow-up was available for eight patients for 6 to 21 months (average, 12 mo). No tumor recurred locally or metastasized. The SFTs reported herein support the experiences of others who recently described these tumors in the somatic soft tissues. In addition, our series highlights the occurrence of malignant SFTs in the soft tissues. SFTs should be separated from other spindle cell sarcomas, with which they can be confused.     

Incidence, consequences, and risk factors of early reocclusion after primary and/or rescue percutaneous transluminal coronary angioplasty for acute myocardial infarction

We recently experienced a 43-year-old man with a large, multiloculated, cystic tumor that appeared on the pelvis. The tumor was composed of glands and cysts lined by prostatic-type epithelium and attached microscopically to the prostate by a pedicle. The prostatic nature of the lesions was confirmed by immunohistochemical staining of epithelium for prostate specific antigen (PSA). Our review of literature disclosed nine similar cases in men of various ages, originated from the prostate and grew to massive proportions. The lesions in these reported cases did not invade contiguous structures but they can adhere to viscera in their proximity. The multilocular prostatic cystadenoma is a pathologically benign entity, and they can be definitively treated by a carefully planned complete surgical excision. This lesion should be included in the differential diagnosis of retroperitoneal cystic tumors in man. We report a rare case of multilocular prostatic cystadenoma that did not invade adjacent organs and showed no evidence of recurrence after complete surgical excision.     

Modulation of the enzymatic properties of protein phosphatase 2A catalytic subunit by the recombinant 65-kDa regulatory subunit PR65alpha

In situ estrogen synthesis by hormone-dependent breast cancers could potentially regulate cellular proliferation through autocrine or paracrine mechanisms. Several biochemical studies have demonstrated activity of the enzyme aromatase, the rate-limiting step for estrogen synthesis, in breast tumor homogenates. Prior immunohistochemical studies in breast neoplasms demonstrated aromatase antibody binding to both stroma and parenchyma, but biochemically measured enzyme activity significantly correlated only with the level of staining in the stromal component. The present study sought to provide more direct evidence of the predominant role for stromal cell aromatase in breast tumor tissue. Accordingly, breast tumor stromal and epithelial cells were examined for aromatase enzyme activity and messenger ribonucleic acid (mRNA) expression. Stromal and epithelial cells from benign tissue served as a means of comparing activity and regulation in benign and tumor tissue. Enzyme activity in stromal cells from breast tumor tissue was low basally, but increased by 30- to 1200-fold when induced by dexamethasone. Combining dexamethasone with phorbol esters and cAMP produced an additional 1.2- to 4.1-fold stimulation. Analyses of exons III/V and exons IX/X demonstrated that aromatase mRNA expression was also substantially increased by these treatments. Increases in enzyme activity and mRNA expression in cells from benign breast stroma paralleled those observed in tumor stroma, although the increases in enzyme activity were generally lower. In contrast to the responses observed in stromal cells, epithelial cells from breast tumor or nonmalignant breast tissue were unresponsive to dexamethasone, either added alone or in combination with phorbol esters and cAMP. This study provides direct biochemical evidence that aromatase is present in stroma within breast tumors, as in surrounding tissues, and suggests that estrogen synthesis within the tumor may modulate tumor growth via a paracrine mechanism.     

Stromal development in the ventral prostate, anterior prostate and seminal vesicle of the rat

The prostate and seminal vesicle (SV) are androgen-dependent secretory glands of the male genital tract. They produce the bulk of the seminal secretions. The object of the present study was to examine and document the ontogeny of stromal maturation in the rat anterior and ventral prostate and SV. These organs have a loosely organized cellular mesenchyme during fetal development. During prostatic development the mesenchyme condensed to form smooth muscle sheaths immediately surrounding the epithelium, with looser connective tissue between individual ducts. In the SV, a loose connective tissue layer called the lamina propria lies between the epithelium and developing muscle. Smooth muscle alpha-actin, myosin, desmin, laminin, vinculin, vimentin and androgen receptor (AR) expression were examined by immunocytochemical methods during the pre- and postnatal developmental periods. The first marker to be detected was vimentin, which was initially found throughout the mesenchyme. During development vimentin became mostly restricted to the interductal tissue of the prostate and the lamina propria of the SV. Smooth muscle markers were expressed in an orderly sequence in a proximal to distal manner along prostatic ducts, from the urethra towards the tips. Expression of alpha-actin was followed by vinculin, myosin, desmin, and laminin. These markers became localized to the developing smooth muscle sheaths and were not expressed in the interductal tissue of the prostate or the lamina propria of the SV. Organ culture experiments demonstrated that androgens were required for the differentiation of smooth muscle sheaths. Castration of adult rats demonstrated that androgens were required to maintain smooth muscle differentiation. In castrates, the stroma was relatively thicker but less dense than in intact animals. Following castration, expression of the smooth muscle markers was lost sequentially in the reverse order of their expression during development. In long-term castrates alpha-actin, vimentin and a small amount of vinculin were detected. AR were first detected in the urogenital sinus mesenchyme immediately surrounding the epithelium at 16 days of gestation. As development progressed expression of AR became more widespread, and postnatally was found throughout the mesenchyme. As maturation of smooth muscle occurred, stromal expression of AR became localized to the muscular sheath immediately surrounding the epithelium. In the prostate the interductal connective tissue displayed very low levels of AR expression. In the SV, AR were also observed in the lamina propria. In summary, stromal differentiation and dedifferentiation in the rat prostate and SV were found to be androgen-dependent processes with ordered sequential ontogenic expression of specific markers.     

Restoration of localized severely atrophic maxillary ridge: case report

Phyllodes tumors are mixed tumors of the mammary gland. They account for 0.3 to 0.5 per cent of all breast tumors. This is a report on nineteen cases presenting phyllodes tumors. Depending on the number of mitoses, growth pattern and atypism degree, the neoplasms are classified as benign (12 cases), borderline (2) and malignant (5). Fourteen of them (9 with benign and 5 with malignant phyllodes tumors) undergo clinical follow-up study. A case with bilateral location of the neoplasm exhibiting strongly expressed susceptibility to relapse is described. The basic methods of preoperative diagnosis and the operative treatment procedures used are outlined.     

Distribution of lipochrome pigment in the prostate gland: biological and diagnostic implications

Lipochrome pigment is characteristically found in Wolffian duct-derived structures including seminal vesicles and ejaculatory ducts. The presence of lipochrome pigment is helpful in identifying atypical histological patterns of seminal vesicle or ejaculatory duct that mimic prostatic adenocarcinoma. The authors studied the distribution of lipochrome pigment in 28 radical prostatectomy specimens using a modified Ziehl-Neelson stain and fluorescence microscopy. In all cases secretory epithelium of the central zone contained lipochrome pigment often in significant amounts (2 to 3+). Secretory epithelium from peripheral and transition zones in each of four specimens (14.3%) contained lipochrome pigment. In addition, occasional examples of nodular hyperplasia, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma contained lipochrome pigment. The preferential distribution of lipochrome pigment in central zone epithelium adds further support to the hypothesis that central zone glands are derived embryologically from Wolffian duct (mesoderm) rather than urogenital sinus (endoderm), which gives rise to transition and peripheral zone glands. Furthermore, lipochrome pigment should not be used as the sole diagnostic criterion for separating atypical histological patterns of seminal vesicle and ejaculatory duct from those of prostatic origin.     

Intramuscular myxoma: a clinicopathologic study of 51 cases with emphasis on hypercellular and hypervascular variants

Intramuscular myxoma (IM) is a benign soft-tissue tumor that presents as a deeply seated mass confined to skeletal muscle. Surgical excision is virtually always curative. Recurrence, even after incomplete resection, is exceptional. Intramuscular myxoma is classically described as hypocellular and hypovascular, and is composed of cytologically bland stellate and bipolar fibroblasts separated by abundant extracellular myxoid matrix. What is underemphasized, however, is that IMs often show areas of increased cellularity and vascularity that can lead to a mistaken diagnosis of sarcoma, especially myxofibrosarcoma, low-grade fibromyxoid sarcoma, and myxoid liposarcoma. In this report, we describe the clinicopathologic features of 51 IMs with special emphasis on those that exhibit these "hypercellular regions." The patients included 35 women and 16 men who ranged in age from 27 to 89 (mean 52) years. The tumors measured from 2 to 15 (average 5.6) cm and all had a gelatinous, lobulated cut surface. Histologically, they all demonstrated classic hypocellular, hypovascular regions. Thirty-eight tumors contained areas of relative increased cellularity that occupied from 10 to 80% of the tumor. These foci had increased numbers of cells, more prominent vascularity, and often increased collagen content. The hypercellular regions were not associated with cytologic atypia of the constituent cells, mitotic activity, or necrosis. Follow-up information was available for 32 patients and ranged from 3 to 108 (average 30) months. No tumor recurred or metastasized. Areas of hypercellularity are common in IMs. Their recognition is important to avoid an erroneous diagnosis of sarcoma.     

Benign fibromatous tumors of the testis and paratesticular region: a report of 9 cases with a proposed classification of fibromatous tumors and tumor-like lesions

Benign intrascrotal fibrous proliferations are uncommon, with most arising from the paratesticular region and falling into the category of so-called fibrous pseudotumor. We describe two neoplastic forms of benign fibrous tumor of the testis and its adnexa: fibroma of gonadal stromal origin and fibroma of the testicular tunics. Three patients with gonadal stromal fibroma were 28, 33, and 35 years of age and presented with painless masses. The tumors were circumscribed, intratesticular, yellow-white or white lesions 0.9 to 4.0 cm in diameter and had microscopic features identical to those of the ovarian fibroma. Immunohistochemically, the tumor cells were strongly positive for vimentin (3/3 cases), focally positive for actin and desmin (2/3 cases) and negative for S-100, keratin, and CD34 (3/3 cases). Six fibromas of the testicular tunics arose in patients 22, 34, 60, 68, 70, and 74 years old and were also asymptomatic masses. Four of them were circumscribed, whorled, white masses arising from the tunica albuginea with variable areas of myxoid change; one was pedunculated and grew exclusively into the cavity of the tunica vaginalis, whereas the other three at least partially extended into the testis as well. The other two tumors were unattached to the tunica albuginea and presented as circumscribed, white-tan paratesticular masses, partially covered by tunica vaginalis. Microscopically, the tumors were slightly to moderately cellular, with bland spindle or stellate cells lying in a myxoid or collagenous stroma with prominent vessels. The two paratesticular tumors had features typical of solitary fibrous tumor. Immunohistochemically, the fibromas of the testicular tunics were negative for S-100, keratin, and desmin. Focal, weak reactivity for actin was present in one case. CD34 was positive in three cases; in the two tumors resembling solitary fibrous tumors it was strong, and in the other it was focal and was limited to the region just below the tunica vaginalis. Eight tumors were treated by radical orchiectomy and one by excision of the mass alone. The outcome was benign in the seven cases in which followup information is available.     

Cytopathology of retrograde renal pelvis brush specimens: an analysis of 40 cases with emphasis on collecting duct carcinoma and low-intermediate grade transitional cell carcinoma

We report our experience with 40 retrograde renal brush samples of pelvic-calyceal lesions with confirmatory tissue studies. On-site cytopathologic evaluation was performed in 38 of these specimens. The final histologic diagnoses included 24 cases of transitional cell carcinoma (TCC), 17 of which were low-intermediate grade tumors. All 24 cases were diagnosed cytologically as TCC (22), or as suspicious for TCC (2). Three cases classified as collecting duct carcinomas were resected; the cytologic specimens in 2 of these cases were interpreted as TCC, and one as reactive change. There were three renal cell carcinomas (RCC); cytologically, one was considered a papillary neoplasm, one suspicious for malignancy, and one as reactive. Two cases of atypical renal cysts were reported as suspicious for malignancy in both cytologic and histologic material. There was one case of metastatic colon carcinoma identified in the brush specimen. Finally, tissue studies in the remaining 7 cases showed reactive/inflammatory changes; however, four of the corresponding pelvic brush specimens were considered abnormal. A review of the above cases is reported with the objective of presenting the cytologic features seen in collecting duct carcinoma, low-intermediate grade TCC, and diagnostically difficult cases with cyto/histomorphologic discrepancies. The contribution of on-site assessment to diagnostic accuracy is also discussed.     

Short-term preservation of autogenous vein grafts: effectiveness of University of Wisconsin solution

BACKGROUND: Regional variations in stromal-epithelial interactions, mediated through soluble growth factors, may be responsible for differences in epithelial growth and death observed between regions of the rat prostatic ductal system. Since transforming growth factor-beta 1 (TGF-beta 1) can induce prostatic epithelial cell death in vitro and in vivo, we examined the localization and production of TGF-beta 1 with respect to the functional regions of the rat prostatic ductal system. METHODS: The distribution of TGF-beta 1 in the rat ventral prostate was examined by immunohistochemistry. Cell type-specific expression of TGF-beta 1 was determined using RT-PCR analysis of prostate epithelial and stromal cell fractions separated by Percoll gradient centrifugation. RESULTS: Immunohistochemical staining of normal prostate revealed regional variations in stromal TGF-beta 1 protein, which was most abundant in the stroma surrounding the degenerative proximal ducts. TGF-beta 1 staining was also tightly associated with the prostatic smooth muscle. Results of RT-PCR experiments confirmed the major source of TGF-beta 1 mRNA in normal rat prostate to be the stroma, with lesser expression by the epithelium. CONCLUSIONS: Stromal TGF-beta 1 was associated with cell death in the adjacent epithelial cell compartment in the prostatic ductal system, and alpha-smooth muscle actin-positive stromal cells may play a negative growth-regulatory role in the rat ventral prostate through production of TGF-beta 1.     

The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases

BACKGROUND: The study addresses the controversial prognostic and therapeutic aspects of phyllodes tumor of the breast. METHODS: Records of 170 women with phyllodes tumor of the breast were reviewed. On the basis of the criteria proposed by Azzopardi and Salvadori et al., including estimation of tumor margin, growth of the connective tissue component, mitoses, and cellular atypia, the entire series was divided into three histotypes of phyllodes tumor, i.e., benign (92 cases, 54.1%), borderline (19 cases, 11.2%), and malignant (59 cases, 34.7%). Ninety-eight patients (57.6%) were treated by wide local excision (79 benign, 15 borderline, and 4 malignant), 43 (25.3%) by simple mastectomy (13 benign, 4 borderline, and 26 malignant), and 29 (17.1%) by radical mastectomy (all malignant). RESULTS: Of the 170 treated patients, 141 (82.9%) survived 5 years without evidence of disease. In the Cox multivariate analysis the histotype of the tumor was the only independent prognostic factor: 5-year NED survival was observed in 95.7% of the patients with benign phyllodes tumor, 73.7% with borderline phyllodes tumor, and 66.1% with malignant phyllodes tumor. After a wide local excision 98.7% of the patients with benign tumor, and 80% with borderline tumor, were cured. Local recurrence was found in 14 patients (8.2%) (4 benign, 3 borderline, and 7 malignant); 10 of these underwent reoperation (7 wide local excision, 3 radical mastectomy) and survived 5 years NED. CONCLUSIONS: The histotype of phyllodes tumor (benign, borderline, and malignant), assessed on the basis of the criteria proposed by Azzopardi and Salvadori et al., was the only prognostic factor in our group of patients. Based on the data from literature and our own observations, we observed that a wide local excision, with an adequate margin of normal breast tissue, is the preferred initial therapy for phyllodes tumor of the breast.