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Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

At least 37 records · Page 2Linked to original sources
PubMed2006

Specialized stromal tumors of the prostate: a clinicopathologic study of 50 cases.

Specialized stromal tumors of the prostate encompass stromal sarcoma and stromal tumors of uncertain malignant potential (STUMP). As a result of their relative rarity and lack of long-term follow-up, the prognosis of STUMP is unclear. We studied 50 cases of STUMP and stromal sarcoma with regard to their clinical presentation and follow-up. Patients ranged in age from 27 to 83 years (mean 58 years). The major presenting signs and symptoms were urinary obstructive symptoms (n=25), abnormal digital rectal exam (n=15), hematuria (n=7), hematospermia (n=1), and rectal dysfunction/fullness (n=3). An elevated prostate-specific antigen was either the sole or a compounding rationale for initial urologic examination and prostate biopsy in a subgroup of patients (n=11). The histology in the 36 cases of STUMP not associated with sarcoma were as follows: 25 composed of stroma with scattered cytologically atypical cells associated with benign glands; 8 resembling glandular-stromal hyperplasia but with hypercellular stroma; 6 with extensive myxoid stroma; and 1 with phyllodes pattern. Four of these cases had mixed patterns. Seven cases of STUMP were associated with sarcoma, either concurrently or subsequently. In another 7 cases, pure sarcomas were encountered: 3 low grade (LG) and 4 high grade (HG). In 19 STUMPs, the location of the lesion was determinable: 10 cases arose in the peripheral zone, 7 cases were located in the transition zone, and 2 cases seemed to involve both zones. In 3 of these cases, tumors were adherent to the rectum at the time of resection. There was no evidence of progression of disease for 14 STUMPs after biopsy, TUR, or enucleation where follow-up ranged from 0.3 to 14 years (mean 4.9 years). Five cases of STUMP showed local tumor growth: 1 case increased in size from 6 to 7.5 cm in 3 years and 4 cases recurred frequently necessitating multiple TURs of the prostate (n=2, n=3, n=3, n=3) over 1.1, 2, 7, and 8 years, respectively. Fourteen patients with STUMP underwent radical prostatectomy (RP) soon after diagnosis; of these, 12 were organ confined where the tumor size ranged from 0.7 to 7.5 cm (mean 2.7 cm); 2 cases with a history of a 28 g TUR and a 275 g enucleation showed no residual tumor in the RP specimen. Three cases were lost to follow-up. The histologic subtypes of STUMP did not correlate with the clinical behavior or likelihood of being associated with sarcoma. Two of the LG sarcomas locally invaded around the seminal vesicle, yet all of the LG sarcomas with follow-up were free of disease at 3, 13, 24, 25, 30, and 36 months. Of the 6 HG sarcomas with follow-up, 3 were free of disease at 3, 17, and 72 months. One man was alive with metastasis to the lung 10 months after RP, 1 man was alive at 280 months with multiple metastases, and another died of disease at 115 months. STUMPs can recur frequently, occur at a young age, often involve the peripheral zone where they can be adherent to the rectum requiring its removal, and can be associated with stromal sarcoma. Although STUMPs can be histologically misdiagnosed as nodular hyperplasia, it is important to recognize that these are neoplasms with unique local morbidity and malignant potential. Whereas LG stromal sarcomas can locally invade, HG sarcomas can metastasize and lead to death.

Adolescent↗
PubMed2006

Inverted papillomas of the prostatic urethra.

Inverted papillomas of the genitourinary tract are uncommon benign neoplasms usually occurring in the urinary bladder and less frequently in the upper urinary tract. To date, there are scant data and no comprehensive studies of inverted papilloma originating in the prostatic urethra. We identified 21 cases and evaluated their demographic, clinical, and histopathologic features. Patients had a mean age of 65.1 years (range: 30 to 89 y), with 10/21 (47.6%) presenting with gross hematuria (n = 8) or irritative symptoms (n = 2) related to the inverted papilloma and 11/21 (52.4%) detected incidentally during work-up/treatment of prostate cancer (n = 6) or benign prostatic hypertrophy (BPH) (n = 5). Fourteen cystoscopically evaluated lesions measured 0.1 to 2.0 cm, and were described as polypoid (n = 9), papillary (n = 4), or an enlarged median lobe (n = 1). Lesions were diagnosed on transurethral resection (n = 8), biopsy/polypectomy targeted to the lesion (n = 6), radical prostatectomy for prostate cancer (n = 4), or biopsy unrelated to the lesion (n = 3). Histologically, 14/21 cases (67%) displayed classic inverted papilloma architecture. The remaining cases showed foci of squamous metaplasia with moderate atypia (n = 4), rare true papillary fronds in a classic inverted papilloma background (n = 2), or both (n = 1). Eleven cases with prostatic tissue revealed adenocarcinoma of the prostate [n = 6; Gleason score 6 (n = 3) or 7 (n = 3)], high-grade prostatic intraepithelial neoplasia (n = 1), benign prostatic hypertrophy (n = 3), or adenosis (n = 1). No patients had a prior history of either inverted papilloma or urothelial carcinoma, whereas 2 patients were diagnosed with high-grade urothelial carcinoma of the bladder synchronous with their inverted papilloma diagnosis. Only 1 of the 18 patients with available follow-up had a recurrence of inverted papilloma in the prostatic urethra. None of the other patients had local recurrences or recurrences at other locations in the urinary tract (mean follow-up 39.9 mo; range: 3 to 120 mo). Inverted papillomas of the prostatic urethra are benign lesions that are commonly detected incidentally and are not associated with a history of urothelial malignancy. Although urothelial carcinoma elsewhere in the genitourinary tract may occur simultaneously, malignant transformation or recurrence as a malignant lesion has not been identified in inverted papilloma of the prostatic urethra.

Adenocarcinoma↗
PubMed2006

Prognostic significance of paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate.

The prognostic significance of Paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate has not yet been established. We studied 36 cases of adenocarcinoma of the prostate showing Paneth cell-like neuroendocrine differentiation, including needle biopsy specimens (n = 27), radical prostatectomies (n = 8), and transurethral resection specimens (n = 1). Paneth cell-like neuroendocrine cells (NECs) were observed as either patchy isolated cells or diffusely involving glands or nests. With Gleason pattern 3, a patchy pattern of NECs was seen in 18/19 cases with only 1/19 (5.3%) case showing diffuse NECs. All the 4 Gleason pattern 4 cases had patchy NECs. Of the 21 cases with Gleason pattern 5, 18 (85.7%) had diffuse NECs with the remaining 3 exhibiting patchy NECs. Radical prostatectomy was performed in 16/36 (44.4%). Tumor was organ confined in 10/16 cases (62.5%). Extraprostatic extension (EPE) with positive surgical margins was seen in 6/16 cases (37.5%). In 4 cases, seminal vesicles were positive for cancer. Pelvic lymph nodes were free of tumor in all cases. The actuarial prostate specific antigen progression-free risk at 5 years and 7 years was 92% and 80%, respectively. Only 2 patients progressed after radical prostatectomy and they both had Gleason score 7 cancer with extraprostatic extension and seminal vesicle invasion. Of the 16 radical prostatectomy cases, 8 (50%) had a Gleason pattern 5 component either on needle biopsy or at radical prostatectomy, with nests, cords, or single cells containing Paneth cell-like neuroendocrine differentiation. Five of these 6 cases with Gleason pattern 5 and available follow-up information had no evidence of progression with mean and median follow-ups of 46 months. Radiation therapy either as monotherapy or combined with hormonal therapy was used to treat patients in 13/36 cases. Overall only 2 patients progressed, one with clinical T2 and the other T3 disease. Of the 5 cases with Gleason pattern 5 composed in part or totally by NECs treated by radiation therapy, all are without evidence of recurrence with a mean and median follow-up of 47 and 45 months, respectively. Of the remaining 5 cases with available follow-up treated with watchful waiting, hormone therapy, or cryotherapy, 4 had Gleason pattern 5 tumor with NECs. Of these 4 cases, 3 had no progression with a mean and median follow-up of 42.5 and 60.5 months, respectively. Despite the cells' bland histologic appearance, strictly applying the Gleason grading system one would have to assign a Gleason pattern 5 to these foci with no glandular differentiation. The current study demonstrates that applying the Gleason score to these foci does not accurately reflect their clinical behavior. In cases with Paneth cell-like NECs, only the conventional adenocarcinoma component should be assigned a Gleason score. In cases in which the entire tumor is composed of Paneth cell-like cells and areas of the tumor lack glandular differentiation, the tumors should not be assigned a Gleason score and a comment should be provided as to the generally favorable prognosis of this morphologic pattern of neuroendocrine differentiation.

Adenocarcinoma↗
PubMed2006

What's new in prostate cancer disease assessment in 2006?

PURPOSE OF REVIEW: Issues relating to the disease are critical in the diagnosis, management, and prognostication of prostate cancer. RECENT FINDINGS: New data have emerged regarding the disease of prostate cancer and its precursors. The diagnosis of prostate cancer on needle biopsy has been refined because of the recent discovery of alpha-methylacyl-CoA racemase, which preferentially labels adenocarcinoma of the prostate. Modifications and additions to the Gleason grading system were published based on a consensus conference of urological pathologists. Various models have been proposed using Gleason score, clinical findings, as well as measurements of tumor volume on needle biopsy to enhance the prediction in men undergoing radical prostatectomy and to predict "insignificance". Several studies have confirmed that certain findings in radical prostatectomy are adverse, yet conflicting studies were published as to the independent prognosis of tumor volume. The risk of cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy has decreased to the point at which this author does not recommend a routine repeat needle biopsy within the first year following the diagnosis of high-grade prostatic intraepithelial neoplasia. SUMMARY: This review summarizes developments over the last year in the disease of prostate cancer and its precursors.

Biopsy, Needle↗
PubMed2006

Update on the Gleason grading system for prostate cancer: results of an international consensus conference of urologic pathologists.

The Gleason system for prostate cancer was based on a study of 270 patients from the Minneapolis Veterans Administration Hospital in 1966-1967. In 1974, Gleason and the Veterans Administrative Cooperative Urological Research Group expanded this study to 1032 men. These studies formed the basis of the Gleason grading system, which is now endorsed as the primary grading system for prostate cancer by the World Health Organization, the Armed Forces Institute of Pathology Fascicle on prostate cancer, the Association of Directors of Anatomic and Surgical Pathology, and the College of American Pathologists. In the nearly 40 years since its inception, several aspects about prostate cancer and its management have changed, most notably serum prostate-specific antigen, transrectal ultrasonography, 18-gauge needle biopsy sampling, immunohistochemistry for the diagnosis of cancer, and radical prostatectomy and radiation therapy as primary treatment modalities. Several aspects of the disease, and consequently the reporting needs, have changed such as reporting cancer on multiple cases in needle biopsies, multiple nodules in prostatectomy, tertiary patterns, variants and variations in prostate cancer. The application of the Gleason system, therefore, has varied considerably in contemporary surgical pathology practice. An International Consensus Conference attended by 80 urologic pathologists from 20 countries was convened to discuss clarifications and modifications to the Gleason system. This article serves as a brief overview and summary of the proceedings that have been published in detail in recent literature.

Adenocarcinoma↗
PubMed2006

Polyoma virus-associated cellular changes in the urine and bladder biopsy samples: a cytohistologic correlation.

Polyoma (BK) virus-type cellular changes are occasionally reported in urine specimens, yet rarely detected in histologic sections of bladder biopsies. A total of 762 predominantly voided urine specimens with a cytologic diagnosis of polyoma virus-type change were retrieved from the cytopathology files of the Johns Hopkins Hospital over a 15-year period (1988-2003). Biopsies were available for 33 cases (29 patients) following or preceding the urinary cytology (mean interval, 210 days). The biopsies originated primarily from bladder (n=31) with one biopsy each from renal pelvis and urethra. Representative paraffin blocks were chosen from each case for immunoperoxidase staining with SV40 large T antigen. There were 22 males and 7 females with an age range of 34 to 79 years (mean, 64.7 years). The histologic diagnoses of the 33 tissue biopsies were: benign urothelium (n=9), urothelial carcinoma (n=21) and 1 case each of dysplasia, small cell carcinoma, and chronic lymphocytic leukemia involving lamina propria of the bladder. Only 3 of 33 biopsies on hematoxylin-stained sections showed morphologic changes of polyoma virus, which lacked sufficient tissue to perform immunohistochemistry for SV40 large T antigen (LTag). Immunohistochemical staining for LTag was positive in 7 cases. Only 2 cases showed strong/diffuse and moderate/focal staining for LTag with both representing invasive high-grade urothelial carcinoma (where no inclusions were seen on hematoxylin and eosin-stained sections) and both demonstrating positive immunostaining for p53. One of these 2 cases was from an organ transplant recipient and the other from a patient with no known immunosuppression. Our data lead to the following conclusions: 1) cytology appears to be more sensitive than histology in detecting cells with polyoma virus; 2) cytohistologic discordance might be due to: a) polyoma (BK) virus infected cells are shed from the tissue and collected in the urine; b) polyoma virus changes may be focal and not sampled in directed tissue biopsies; c) polyoma virus changes may originate from sites in the genitourinary tract other than the bladder; d) the lack of a "gold standard" to confirm the cytologic diagnoses of polyoma virus; and e) the discordance in time between the biopsy and cytology specimens in the current retrospective study. 3) Because some cytologically benign cases of polyoma virus were associated with malignant biopsies, careful morphologic evaluation is required to avoid false-negative urinary cytology samples. This investigation further examined the immunohistochemical staining pattern for SV40 LTag and p53 in noninvasive low-grade papillary urothelial carcinoma using a tissue microarray constructed from bladder biopsies of 79 randomly selected patients. Weak LTag staining was present in occasional neoplastic urothelial cells of 2 patients. The staining was present in only one of four samples from each tumor (0.63%; 2 of 316 tumor spots), which further illustrates the patchy and focal presence of virion containing cells. p53 staining in these two spots was also patchy and confined to rare nuclei.

Adult↗
PubMed2006

Angiomyolipoma with epithelial cysts (AMLEC): a distinct cystic variant of angiomyolipoma.

Renal angiomyolipoma (AML) is typically a solid lesion, composed of varying amounts of adipose, vascular, and muscular tissue, lacking an epithelial component. Although it is known that entrapped renal tubules may be observed in AML, presentation as a cystic mass has not been previously reported. We report the clinicopathologic and immunohistochemical features of four cystic renal AML. The lesions were found in 2 male and 2 female patients, ranging in age from 37 to 76 years, none with a history of hormonal therapy. One of the four patients had known tuberous sclerosis, and this patient and 1 other presented with bilateral cystic renal lesions. Grossly, the lesions measured between 1.3 and 4.5 cm in greatest dimension. Histologically, the lesions were each composed of three components: 1) epithelial cysts lined by cuboidal to hobnail cells; 2) a compact subepithelial "cambium-like" layer of cellular, müllerian-like AML stroma with prominent admixed chronic inflammation; and 3) muscle-predominant AML with associated dysmorphic blood vessels exterior to the cellular subepithelial stroma. Immunohistochemically, the stromal components of all four lesions labeled with HMB-45 and Melan-A, most intensely in the cellular subepithelial stroma, whereas smooth muscle actin and desmin demonstrated the opposite pattern, with greatest intensity in the muscle-predominant AML areas. Immunoreactivity for estrogen and progesterone receptors (ER, PR) and CD10 was present in all cases, with strongest and most diffuse staining in the subepithelial AML cells. The cyst lining cells were positive for pancytokeratin and soy bean agglutinin (the latter characteristic of distal nephron epithelium) but did not label for ER, PR, or melanocytic markers. Although these distinctive lesions may be confused with mixed epithelial-stromal tumor, their lack of female predominance or association with hormone therapy, their distinctive dysplastic blood vessels and disorganized exterior muscular layer, along with their immunohistochemical profile, support their classification as AML with epithelial cysts. Whereas the cysts appear to arise primarily from entrapped collecting ducts, the peculiar subepithelial condensation of AML stromal cells, with morphologic and immunohistochemical features suggesting differentiation toward endometrial stroma, may represent epithelial-induced müllerian differentiation not previously reported in AML.

Adult↗
PubMed2006

Sarcomatoid carcinoma of the prostate: a study of 42 cases.

UNLABELLED: Sarcomatoid carcinoma of the prostate is a rare type of prostatic cancer. With the exception of 1 study, the morphologic features and patient outcomes have been reported only in relatively small case series and individual reports. We examined transurethral resection, needle biopsy, and radical prostatectomy specimens from 42 patients with sarcomatoid carcinoma of the prostate, all of which were received in consultation. Clinical information on 32 patients was obtainable. Five patients were lost to follow-up and information on the 5 remaining patients could not be obtained. Prior prostatic adenocarcinoma: The majority of patients (n=21; 66%) had a prior history of acinar adenocarcinoma of the prostate. Of the 14 men with available data, reported Gleason scores were 6 (n=7), 8 (n=4), and 10 (n=3). Of the remaining patients for whom this information was known, 11 patients presented with de novo sarcomatoid carcinoma. The time between the original diagnosis of acinar adenocarcinoma and diagnosis of sarcomatoid carcinoma ranged from 6 months to 16 years (mean 6.8 y). Concurrent adenocarcinoma: The majority of patients demonstrated a concurrent high grade acinar carcinoma of Gleason score 7 (n=3), 8 (n=9), 9 (n=10), and 10 (n=10). A subset of patients contained an admixed ductal adenocarcinoma (n=4), small cell carcinoma (n=3), squamous cell carcinoma (n=3), or other unusual pattern of prostate carcinoma (n=3). In 1 case, the diagnosis was based on immunohistochemical evidence of epithelial differentiation along with the history of prior adenocarcinoma. Morphology of the sarcomatoid component: The percentage of sarcomatoid growth ranged from 5% to 99% (mean 65%). Bizarre atypia with giant cells was present in 55% of cases. Admixed heterologous elements were identified in 10 cases (29%), including osteosarcomatous (n=7), chondrosarcomatous (n=5), and rhabdomyosarcomatous (n=2) elements. Of the 12 cases with received immunostains of the sarcomatoid component, 5/7 cases were at least focally positive for cytokeratin, 1/1 case was focally positive for Cam5.2, and 3/6 cases were focally positive for prostate acid phosphatase. The sarcomatoid component did not demonstrate immunoreactivity for prostate-specific antigen in 8 cases. PROGNOSIS: approximately half of all patients developed metastatic disease either at time of presentation or subsequently. Of patients with meaningful follow-up, 6/7 died within 1 year of the diagnosis of sarcomatoid carcinoma; 20 were alive yet with very short follow-up (median 1 y; mean 2.3 y). Kaplan-Meier analysis revealed that the actuarial risk of death at 1 year after diagnosis of sarcomatoid carcinoma was 20%. No correlation was identified between patient survival and morphologic features, before radiation or hormone therapy, or concurrent high-grade prostate cancer. Sarcomatoid carcinoma demonstrates diverse spindle and epithelial cell morphologies. The sarcomatoid component often has heterologous elements and, in 1 case, no epithelial component was seen on hematoxylin and eosin-stained sections. The epithelial component is typically high-grade acinar adenocarcinoma, yet other aggressive tumor subtypes such as ductal adenocarcinoma and small cell carcinoma may also be seen. Sarcomatoid carcinoma is an aggressive form of prostate cancer, the prognosis of which is dismal regardless of other histologic or clinical findings.

Aged↗
PubMed2006

Pleomorphic giant cell adenocarcinoma of the prostate: report of 6 cases.

Pleomorphic tumors with giant cells have been described in a variety of primary sites. However, only a few cases have been described among prostatic carcinomas with only 1 on diagnostic biopsy material. Five cases were retrieved from the consultation files of one of the authors. One of the cases was retrieved from the surgical pathology files at our institute. Patient ranged in age from 59 to 76 years (mean=65.8 y). The diagnosis was made on needle biopsy (n=3), urethral biopsy (n=1), transurethral resection (n=1), or radical prostatectomy (n=1). In all cases, giant, bizarre, anaplastic cells were present. In 4 of the cases, marked pleomorphism occupied 5% of the specimen, with 20% and 70% bizarre giant cells in the other 2 cases. In one case, the bizarre cells had atypical mitotic figures, with other cases showing no mitoses in the markedly pleomorphic cells. In addition to the pleomorphic giant cell component, multiple coexistent histologic components were seen including Gleason score 9 conventional prostate cancer (n=6), small cell carcinoma (n=1), squamous carcinoma (n=1), and prominent ductal adenocarcinoma differentiation with intraductal spread (n=1). Immunohistochemically, 4 cases were for negative for prostate-specific antigen in the giant cells, 1 had 5% staining, and the other had 50% positivity in the giant cells. Staining for prostate-specific antigen in the conventional prostate carcinoma component was 1%, 5%, 20%, 50%, 100%, and 100%. The bizarre giant cells were strongly positive for cytokeratins AE1/AE3 and/or Cam 5.2 (n=3). Two cases had a history of conventional prostate cancer 4 years before the giant cell component, 1 treated with Lupron and the other with radiation. Follow-up after diagnosis of the giant cell component: Case 1: dead in 1 year of disease; Case 2: progressive metastases in 2 years; Case 3: alive at 1 year with disease; Case 4: large perineal recurrence after brachytherapy at 3 years; Case 5: radical prostatectomy with extraprostatic extension and seminal vesicle invasion; and Case 6: alive at 3 months, free of disease. Conventional prostate cancer, even when very high grade, typically consists of cells with relatively uniform nuclei. Our study expands the histology described in prostate cancer to include in very rare cases with prominent pleomorphism and bizarre giant cells. This giant cell component heralds a particularly aggressive clinical outcome.

Adenocarcinoma↗
PubMed2006

Gastrointestinal stromal tumors (GISTs) on prostate needle biopsy: A clinicopathologic study of 8 cases.

Gastrointestinal stromal tumors (GISTs) are typically not included in the differential diagnosis of spindle cell tumors seen on prostate needle biopsy. However, their recognition is critical due to their unique clinical management. We report the rare phenomenon of 8 cases of GISTs diagnosed on prostate needle biopsy. The mean patient age at diagnosis was 53.6 years (range: 42 to 65 years). Tumors variably presented with rectal fullness, urinary obstructive symptoms, and abnormal digital rectal examination. Four tumors were resected. One of these cases was shown to be primary in the rectum without prostatic involvement. The second case extensively involved the prostate but its epicenter was in the rectal muscularis propria. The third case was an encapsulated mass separated by a thin fibrous capsule from the prostate. The fourth case was a perirectal mass that underwent local excision. Four lesions have not been resected. On the basis of imaging studies, one seemed to be a prostatic mass, however, additional imaging investigations showed the mass to be separate from the prostate. Three cases have not yet been studied radiographically. Tumors measured 1.0, 1.7, 5.4, 7.0, 7.4, and 8.5 cm. The sizes of 2 recently diagnosed tumors remain undetermined. Histologically, all 8 GISTs showed spindled cells with a fascicular growth pattern. Additional histologic findings included focal epithelioid features (n = 3), necrosis (n = 3), mitotic rates of >5 per 50 high-power field (n = 2), and cytologically malignant features (n = 3). CD117/c-kit was diffusely positive in all 8 cases and CD34 in 7/8 cases. In all cases studied, stains for S100, desmin, and smooth muscle actin were negative. Two patients were treated with imatinib mesylate. One underwent radical prostatectomy after reduction in tumor size after imatinib administration. Another patient was treated with imatinib for several months with complete tumor response and no residual tumor seen in a subsequent local excision. Rectal or extraintestinal GIST can result in a clinical impression of a prostatic lesion. One should consider CD117/c-kit in the immunohistochemical panel to exclude GIST before diagnosing a solitary fibrous tumor, leiomyosarcoma, or specialized prostatic stromal tumor on prostate needle biopsy.

Adult↗
PubMed2006

Expanding the histologic spectrum of mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinomas (MTSCs) are polymorphic neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied. We identified 17 previously unreported MTSCs from Surgical Pathology and consultative files of the authors and their respective institutions and studied their morphologic features. A total of 10/17 cases were considered "classic," as described above, with 5/10 showing at least focal (20% to 50%) tubular predominance without apparent mucinous matrix. Alcian blue staining revealed abundant (>50%) mucin in all classic cases. Seven of 17 MTSCs were classified as "mucin-poor," with little to no extracellular mucin appreciable by hematoxylin and eosin. Four of these cases showed equal tubular and spindled morphology, 2 cases showed spindle cell predominance (70%; 95%), and 1 case showed tubular predominance (90%). In 5/7 mucin-poor cases, staining for Alcian blue revealed scant (<10%) mucin in cellular areas with the other 2 cases having 30% mucin. Unusual histologic features identified in the 17 cases were: foamy macrophages (n=8), papillations/well formed papillae (n=6/n=1), focal clear cells in tubules (n=3), necrosis (n=3), oncocytic tubules (n=2; 40%, 5%), numerous small vacuoles (n=2), heterotopic bone (n=1), psammomatous calcification (n=1), and nodular growth with lymphocytic cuffing (n=1). An exceptional case contained a well-circumscribed, HMB45-positive angiomyolipoma within the MTSC. MTSCs may be "mucin-poor" and show a marked predominance of either of its principal morphologic components, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, and necrosis, may mimic other forms of renal cell carcinoma. Pathologists must be aware of the spectrum of histologic findings within MTSCs to ensure their accurate diagnosis.

Adenocarcinoma↗
PubMed2006

Distorted rectal tissue on prostate needle biopsy: a mimicker of prostate cancer.

Rectal tissue is often seen in needle biopsies of the prostate gland. On rare occasion distorted rectal glands can mimic prostatic adenocarcinoma, an issue not previously addressed in the peer-reviewed literature. We evaluated 16 prostate needle biopsies received in consultation where the submitting pathologist questioned whether a focus of rectal tissue was prostate cancer. In addition to the distorted architecture, features mimicking prostate cancer included: (1) blue-tinged intraluminal mucinous secretions in 10 cases (63%), (2) prominent nucleoli in 6 cases (37%), (3) mitotic activity in 6 cases (37%), (4) extracellular mucin in 5 cases (31%), and (5) adenomatous changes of the rectal tissue in 1 case (6%). Immunohistochemical results further mimicked prostate cancer with negative stains for the basal cell markers high-molecular weight cytokeratin (n=6) and p63 (n=4), and positive stains for racemase in 4 of 5 biopsies. Diagnostic clues to recognizing that these foci were distorted rectal fragments were the presence of (1) lamina propria in 12 cases (75%), (2) rectal tissue located on a detached fragment of tissue in 10 biopsies (63%), (3) associated inflammation in 10 cases (63%), (4) goblet cells in 7 cases (44%), and (5) muscularis propria in 6 cases (37%). In 2 cases, there was negative staining for prostate specific antigen (PSA) and in 1 case negative staining for cytokeratin 7 and positivity for cytokeratin 20. Rectal glands are associated with many of the classical features of prostate cancer, and immunohistochemistry may be misleading. Recognition of these features mimicking prostate cancer and awareness of other findings that are diagnostic of rectal tissue on biopsy can prevent a misdiagnosis of atypical prostate glands or prostate cancer.

Adenocarcinoma↗
PubMed2006

Inflammatory myofibroblastic tumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma.

Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities. We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC. Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences). Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months. In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but none of our typical cases metastasized, although they can rarely arise contemporaneously with sarcomatoid urothelial carcinomas. For these reasons, close follow-up is warranted.

Adolescent↗
PubMed2006

Noninvasive squamous lesions in the urinary bladder: a clinicopathologic analysis of 29 cases.

Noninvasive squamous lesions are distinctively uncommon in biopsies of the urinary bladder with the exception of nonkeratinizing squamous metaplasia. The clinical significance of these squamous lesions in the bladder remains to be explored. A total of 29 cases of transurethral biopsies and resections of the bladder containing noninvasive squamous lesions (excluding nonkeratinizing metaplasia) were studied from the consult files of one of the authors. These cases included keratinizing squamous metaplasia (5), verrucous squamous hyperplasia (5), squamous papilloma (5), condyloma acuminatum (3), and squamous cell carcinoma in situ (CIS) (11). Immunohistochemistry for epithelial growth factor receptor (EGFR) and in situ hybridization for wide-range human papillomavirus was performed on 23 cases. The follow-up period ranged from 2 months to 3 years with an average of 1.5 years. After the initial diagnoses in biopsies of the bladder, 10 patients received cystectomies, and 7 patients received repeat tissue sampling of the bladder. Of the 5 patients with keratinizing squamous metaplasia, 2 patients had invasive urothelial carcinoma with squamous features in their cystectomy specimens at intervals of 3 and 14 months, respectively, 1 had persistent keratinizing squamous metaplasia on rebiopsy. Of the 5 patients with verrucous squamous hyperplasia, 1 patient had invasive squamous cell carcinoma at cystectomy at an interval of 14 months, 1 had squamous cell CIS on rebiopsy, 1 had persistent verrucous squamous hyperplasia on rebiopsy, and 2 had no evidence of disease at 6 and 24 months. Of the 5 patients with squamous papilloma, 1 patient had low-grade urothelial carcinoma at cystectomy at an interval of 21 months (h/o low-grade urothelial carcinoma preceding papilloma diagnosis), 2 were free of lesions at rebiopsy. Of the 3 patients with condyloma acuminatum, 1 had squamous CIS at cystectomy at an interval of 3 months, 1 had invasive squamous cell carcinoma at 20 months. Of the 11 patients with squamous cell carcinoma in situ (CIS), 3 patients had invasive squamous cell carcinoma at intervals of 2, 3, and 4 months, respectively, 1 had invasive urothelial carcinoma with squamous features in cystectomies at an interval of 12 months, 1 had squamous cell CIS at 10 months, 1 had high-grade urothelial carcinoma (not otherwise specified) at rebiopsy at an interval of 6 months, and 1 had no evidence of disease at 8 months. Among the 9 patients with invasive carcinoma, 4 patients died in the period of 0.5 to 3 years after the diagnoses. Immunohistochemical study with EGFR demonstrated strong signals in 20 cases and no signals in 2 cases. Wide-range human papillomavirus DNA signal was detected in 1 case of condyloma acuminatum and 1 case of squamous cell CIS. Keratinizing squamous metaplasia, verrucous squamous hyperplasia, and condyloma acuminatum in the urinary bladder can be associated with subsequent or concurrent in situ, or invasive squamous carcinoma and should be closely followed. Squamous cell CIS in the urinary bladder is often associated with subsequent or concurrent invasive carcinoma with squamous differentiation. Enhanced expression of EGFR in these bladder squamous lesions suggests that EGFR may represent a logic therapeutic target in those squamous lesions that are difficult to manage clinically.

Adult↗
PubMed2006

A working group classification of focal prostate atrophy lesions.

Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of "training" images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct "test" images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of "standard" diagnoses and the kappa statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median kappa) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the "training set" of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.

Atrophy↗
PubMed2006

Widespread high-grade prostatic intraepithelial neoplasia on prostatic needle biopsy: a significant likelihood of subsequently diagnosed adenocarcinoma.

In comparison with earlier studies, recent reports have demonstrated a lower incidence of prostate carcinoma after an initial diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN). The latter has led to a general tendency to reconsider the absolute need for a rebiopsy in this setting. The current retrospective study assesses the subsequent likelihood of identifying prostatic adenocarcinoma (PCa) in 41 patients with an initial diagnosis of "widespread" HGPIN defined as HGPIN present in 4 or more biopsy cores. All patients underwent at least 1 follow-up (F/U) sampling procedure in a period of 1 to 41 months. PCa was found in 16/41 patients (39%), all except 1 identified on the first F/U biopsy with the remaining patients diagnosed on a transurethral resection after a negative first F/U biopsy. All but 1 prostatic carcinoma diagnoses were obtained within 2 years from initial biopsy with 10 rendered within the first year. On average, prostate cancer was identified at 10.4 months (range: 1 to 36). One-fourth of all identified prostatic carcinomas were of Gleason score 7 or more. In 4 additional patients (9.7%), F/U biopsy revealed HGPIN with adjacent atypical small glands suspicious but not diagnostic of carcinoma (PINATYP). Of 41 patients, 10 (24.3%) continued to show HGPIN with the remaining 11/41 patients (26.8%) showing benign prostatic tissue. Patients >or=70 years of age at the time of initial biopsy had a statistically significant higher rate of PCa or HGPIN/PINATYP diagnosis on repeat biopsy compared with younger patients (P=0.02), with 55% of older men being diagnosed with cancer as compared with 33% in younger men. Patients with fewer cores sampled on initial biopsy were more likely to be diagnosed with carcinoma as opposed to HGPIN/PINATYP on F/U (P=0.015). Other factors such as the number of F/U procedures, serum prostate-specific antigen level before initial HGPIN biopsy, number of cores per F/U biopsy, and F/U interval length did not affect the likelihood of finding carcinoma. In summary, our study reveals a 39% risk of finding PCa on repeat biopsies obtained after an initial diagnosis of widespread HGPIN. Our findings support the need for a repeat biopsy in this subset of patients.

Adenocarcinoma↗
PubMed2006

Malignant solitary fibrous tumor of the kidney: report of a case and comprehensive review of the literature.

Renal solitary fibrous tumors (SFTs) have been reported infrequently. We report a 76-year-old man with a left renal mass that had previously been shown radiographically to be stable, but was now growing. Grossly, the mass measured 12 cm, was poorly circumscribed, and invaded beyond the renal capsule. Approximately 10% of the neoplasm consisted of haphazardly arranged spindle cells admixed with dense collagenous bands, which is typical of benign SFT. However, the remainder of the mass was composed of pleomorphic, spindled sarcoma cells with frequent mitoses and foci of necrosis. Immunohistochemically, we observed CD34 labeling in the benign SFT component with loss of expression in the sarcomatous component, focal labeling for Bcl-2 protein in both areas, and absence of labeling for cytokeratin, renal cell carcinoma marker, S100 protein, CD117, and muscle markers in both areas. To our knowledge, this is the first reported case of malignant renal SFT, likely representing transformation from a histologically documented benign SFT component.

Aged↗