Ovarian Metastases of Breast Cancers With Signet Ring Cells: A Report of 17 Cases Including 14 Krukenberg Tumors.

Krukenberg tumor, defined as metastatic adenocarcinoma to the ovary containing at least 10% signet ring cells, usually arises from the stomach but can also originate from other sites. We reviewed 17 metastatic breast carcinomas to the ovary with signet ring cells to potentially identify features indicative of mammary origin as opposed to other possible primary sites. The patients ranged from 41 to 76 (mean, 53.6) yr. Fourteen had a prior history of invasive breast carcinoma (invasive ductal carcinoma, 4; invasive lobular carcinoma, 3; adenocarcinoma not otherwise specified, 3; carcinoma with ductal and lobular features, 2; and unspecified carcinoma, 2) and metastases were identified 2 to 284 (mean, 79) mo after the original diagnosis. Three patients had no known history of invasive breast carcinoma: 1 was subsequently diagnosed with invasive lobular carcinoma, 1 had suspicious bilateral breast masses identified on imaging, and 1 was lost to follow-up. Bilateral ovarian metastases were present in 87%, and the tumors ranged from 3.8 to 19 (mean, 8) cm. Microscopically the ovarian architecture was effaced in 71% by discrete tumor lobules separated by striking edema. The tumors exhibited a variety of histologic patterns: nests were most common (88%), followed by cords (82%), diffuse sheets (82%), single cells (71%), small clusters (41%), glands (29%), and follicle-like cysts (12%). Signet ring cells comprised 2% to 70% (mean, 33%) of the tumors, with 14 cases meeting the criteria for Krukenberg tumor. Signet ring cells were most frequently observed within diffuse sheets (71%) and cords (65%). Tumor cells arranged in nests, cords, and diffuse sheets are typical of Krukenberg tumor of breast origin, and the patterns recapitulate those seen in primary breast carcinomas. Features characteristic of gastrointestinal origin, such as extracellular mucin, intestinal-type glands, dirty necrosis, microcysts, and goblet cell carcinoid-like foci, were absent. The overall morphologic picture in cases of ovarian spread of breast cancer with signet ring cells is usually strongly suggestive of mammary origin. The diagnosis can be further supported by the clinical history and immunohistochemical evaluation.

Lobular Carcinoma of the Breast Metastatic to the Ovary: A Clinicopathologic Study of 38 Cases.

We evaluated the clinicopathologic features of 38 cases of metastatic lobular (n=33) or predominantly lobular (n=5) carcinoma involving the ovary. The patients were from 39 to 91 years of age (mean: 53 y). In 2 cases, the breast primary and ovarian metastasis were diagnosed synchronously, and in 5, the breast primary was only discovered after the metastatic carcinoma in the ovary was found. In the majority of cases (79%), both ovaries were involved; the mean ovarian tumor size was 5.9 cm. The ovarian tumors demonstrated a range of architectural patterns including macronodular (71%), diffuse/solid growth (87%), single-cell infiltration (87%), cords (74%), and small nests/clusters (50%). Nine cases demonstrated focal signet ring cell morphology. The associated stromal reaction ranged from none to marked, with almost half of cases demonstrating a marked stromal response, largely prominent sclerosis. A variety of neoplasms, most typically sex cord-stromal tumors, lymphoma/leukemia, and desmoplastic small round cell tumor, may enter the differential. In addition to the obvious help afforded in most cases by the clinical history, a combination of judicious sampling, particularly to unearth the delicate cords or single-cell growth of lobular carcinoma, appropriate consideration of the cytologic features of the neoplastic cells, and immunohistochemistry can resolve the diverse issues in differential diagnosis that may arise.

CT-guided needle biopsy: value of on-site cytopathologic evaluation of core specimen touch preparations.

PURPOSE: To examine the diagnostic effect of immediate on-site cytopathologic evaluation of tissue core touch preparations in computed tomographic (CT)-guided coaxial needle biopsy. MATERIALS AND METHODS: The authors reviewed the records of 430 patients and included 413 patients with 432 biopsies (210 in the lungs, 222 in other locations). Each time the guiding needle was moved to a new location in the lesion for tissue core procurement with the cutting needle, it represented a new session. Core specimen touch preparations were obtained and immediately evaluated on-site for specimen adequacy and preliminary diagnosis. New sessions were considered and/or executed in the case of inconclusive cytopathologic readings. Each final diagnosis was reached according to the pathology report showing "positive for malignancy," "negative but with a specific diagnosis," or "unclear" for further surgical resection specimen or radiologic follow-up. RESULTS: The accuracy of on-site cytopathologic examination of touch preparations was 80.6% for the first session and increased to 85.9% and 86.3%, respectively, for the second and third sessions. The corresponding accuracies for biopsy were 88.2%, 93.8%, and 94.9%. The overall accuracy was 97.1% for lesions in the lungs and 92.8% for lesions at other sites. More biopsy sessions were deemed necessary in lesions measuring 2 cm or smaller (P = .0045). During CT-guided lung biopsy, 10 patients (4.8%) had major complications that necessitated chest tube insertion. CONCLUSIONS: The diagnostic accuracy of CT-guided needle biopsy can be increased through repeated sessions with immediate on-site cytologic evaluation, especially for lesions of 2 cm or smaller and those from nonpulmonary sites.

Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis.

The intermediate filament protein Nestin identifies stem/progenitor cells in adult tissues, but the function of Nestin is poorly understood. We investigated Nestin expression and function in common lethal cancers. Nestin mRNA was detected in cell lines from small cell lung, and breast cancers, and particularly elevated in cell lines derived from prostate cancer metastases. Whereas the androgen-independent lines PC3, 22RV1, and DU145 all expressed Nestin transcripts under standard culture conditions, the androgen-dependent line LnCaP expressed Nestin only on androgen withdrawal. We confirmed associations of Nestin expression, androgen withdrawal, and metastatic potential by immunohistochemical analysis of samples from 254 prostate cancer patients. Cytoplasmic Nestin protein was readily identifiable in prostate cancer cells from 75% of patients with lethal androgen-independent disease, even in cancer sampled from the prostate itself. However, Nestin expression was undetectable in localized androgen-deprived tumors and in metastases without prior androgen deprivation. To address its function, we reduced Nestin levels with short hairpin RNAs, markedly inhibiting in vitro migration and invasion in prostate cancer cells but leaving cell growth intact. Nestin knockdown also diminished metastases 5-fold compared with controls despite uncompromised tumorigenicity at the site of inoculation. These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread.

Xanthoma of the prostate: a mimicker of high-grade prostate adenocarcinoma.

Prostatic xanthoma may mimic high-grade prostatic adenocarcinoma or prostate cancer treated with hormone therapy. From 1995 to 2006, 40 cases of prostatic xanthoma were diagnosed at The Johns Hopkins Hospital. Thirty-four cases were received in consultation from outside institutions. Hematoxylin and eosin-stained or unstained slides were available in 27 cases (24 consultation cases; 3 in-house cases). Xanthoma was found on needle biopsy in 25 cases, with 2 cases noted on transurethral resection of prostate. Twenty-six cases contained only 1 focus of prostatic xanthoma with 1 case having 3 foci on the same core biopsy specimen. In 21 xanthomas, the lesions were small measuring 1 mm with the largest one measuring 2.5 mm. Xanthoma cells had small uniform, benign-appearing nuclei, small inconspicuous nucleoli, and abundant vacuolated foamy cytoplasm. No mitoses were identified. Focal necrosis was identified in 1 case. Most xanthomas were arranged in circumscribed solid nodular pattern (17 cases). Ten xanthomas consisted of cords and individual cells infiltrating the prostatic stroma, further mimicking high-grade prostate carcinoma. Two xanthomas contained a mixed circumscribed nodular pattern and infiltrating pattern. Of cases with the lesion still present on slides for immunohistochemistry, CD68 was diffusely strongly positive in 18/19 (94.7%) and CAM5.2 was positive in none of the cases 0/14 (0%). One of 15 (6.7%), 2/17 (11.8%), and 1/12 (8.3%) cases were positive for prostate-specific antigen, prostate-specific acid phosphatase, and alpha-methylacyl-CoA racemase, respectively. Careful attention to morphology with adjunctive use of CD68 and CAM5.2 immunohistochemical stains are helpful in the diagnosis of prostatic xanthoma, especially in difficult cases with an infiltrative pattern.

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (

Nasopharyngeal biopsy imprint cytology: a retrospective analysis of 191 cases.

Patients with nasopharyngeal carcinoma (NPC) are common in Taiwan. To provide efficient management to patients, the surgeons often perform cytological imprints immediately after biopsies of lesions suspicious for NPC. The results of cytological assessment of imprints usually are reported within 30 min after biopsies. The patients with positive cytological results can then be arranged for further examinations during the same visit. We reviewed 191 imprints and corresponding biopsies from 187 patients during 1997-2004 at Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The cytological diagnoses were categorized into four groups: negative (62 cases), suspicious (8 cases), positive (116 cases), and inadequate specimen (5 cases). There were 18 false-negative and 1 false-positive diagnoses. All suspicious cases were positive histologically. Our results showed a sensitivity of 87.2% and a specificity of 97.8%. The accuracy was 89.8%. Therefore, nasopharyngeal imprint cytology is a sensitive and specific method for rapid diagnosis of nasopharyngeal cancer at an outpatient setting.

Extrapelvic endometriosis complicated with colonic obstruction.

Endometriosis is often seen in gynecology practice and is treated medically. However, intestinal involvement of endometriosis causing obstruction is relatively uncommon and is hard to differentiate from malignancy before surgery. Herein, we present a case of acute colonic obstruction caused by rectal endometriosis. Repeat colonoscopic biopsy and imaging studies could not differentiate the lesion from malignancy. Segmental resection with anastomosis was performed to relieve the symptom and confirm the diagnosis. We present this unusual disease in general surgical practice and also review the literature. The incidence, symptoms, diagnosis, treatment, and risk of malignancy of intestinal endometriosis are discussed.

Mycobacterium abscessus granulomatous prostatitis.

Infectious granulomatous prostatitis is uncommon, and most cases of granulomatous prostatitis are classified as nonspecific granulomatous prostatitis. From 2007 to 2009, 5 patients experienced poor wound healing after radical prostatectomy for prostate cancer at a specialist cancer center. Mycobacterium abscessus was cultured from the debridement specimens, and acid-fast-positive bacilli were identified histologically within the prostates. All 180 radical prostatectomy specimens from May 2007 to June 2009 were reviewed, and 7 additional cases with morphologies suspicious of M. abscessus granulomatous prostatitis (MAGP) were identified. The characteristic morphologic feature of MAGP was suppurative necrotizing granulomatous inflammation extensively (10% to 80% of the gland; mean, 39%) involving the prostate. The centers of MAGP were large areas of neutrophilic abscess and necrotic debris, which were surrounded by histiocytes, lymphocytes, plasma cells, scattered multinucleated giant cells, and eosinophils. In the adjacent areas, there was a lobular extension of mixed inflammatory infiltrates into dilated and ruptured ducts. Involvement of extraprostatic soft tissue and seminal vesicles/vas deferens was found in 9 and 4 cases, respectively. Acid-fast-positive bacilli were identified in 5 radical prostatectomies. Eleven patients had fresh tissue specimens stored at -150°C, and M. abscessus was cultured from 8 prostates. Random amplified polymorphic DNA-polymerase chain reaction showed the same clone for all isolates. After prostatectomy, 8 patients experienced prolonged wound healing, with urethrorectal fistula formation in 1 patient and a pelvic abscess in another. It is critical for pathologists to recognize MAGP and to distinguish it from the more common nonspecific granulomatous prostatitis and other granulomatous lesions within the prostate.

Positive surgical margins in areas of capsular incision in otherwise organ-confined disease at radical prostatectomy: histologic features and pitfalls.

Capsular incision (CI) refers to the urologist transecting either benign or malignant prostatic tissue, where the edge of the prostate in this region is left within the patient. Histologic assessment of CI is difficult and its diagnosis varies among pathologists. Between 1993 and 2004, we reviewed 186 radical prostatectomies that were signed out as either: (1) CI into tumor in otherwise organ-confined disease [elsewhere no extra-prostatic extension (EPE), seminal vesicle invasion, or lymph node spread] (n=143); (2) positive surgical margin in an area difficult to distinguish EPE from CI into tumor in otherwise organ-confined disease (n=36); or (3) equivocal positive surgical margin in an area difficult to distinguish organ-confined disease with tumor close to resection margins (OC M-) from CI into tumor in otherwise organ-confined disease (n=7). On review, CI with a positive margin was confirmed in 83.2% of cases. Of cases signed out with margins positive where it was difficult to distinguish CI from EPE, CI was confirmed in 52.8% of cases. Cases with equivocal positive margins with either CI or OC M- were considered CI with positive margins in 57.1% of cases on review. Cases in all 3 groups not considered positive margins with CI were on review equally divided between diagnoses of organ-confined margin negative and EPE with positive margins. The locations of the 39 cases originally misdiagnosed as definitive or questionable CI with positive margins were posterolateral (N=19, 48.7%), distal (N=12, 30.8%), posterior (N=6, 15.4%), and anterolateral (N=2, 5.1%). Familiarity with different patterns of EPE in different anatomic locations and applying strict criteria for diagnosing CI into tumor can minimize overcalling CI and can provide accurate feedback to urologists to prevent iatrogenic positive margins.

The significance of positive surgical margin in areas of capsular incision in otherwise organ confined disease at radical prostatectomy.

PURPOSE: The significance of capsular incision into tumor at radical prostatectomy with otherwise organ confined tumor is not well understood. MATERIALS AND METHODS: Inclusion criteria were positive margin in an area of capsular incision, no extraprostatic extension elsewhere, negative seminal vesicles and lymph nodes, entire prostate submitted for examination, and no neoadjuvant therapy. RESULTS: The postoperative progression of 135 cases of radical prostatectomy with capsular incision (1.3% of radical prostatectomies 1993 to 2004) was compared to 10,311 radical prostatectomies without capsular incision. Mean tumor length at the capsular incision site was 2.6 mm. Capsular incision was posterolateral (61.5%), posterior (18.5%), anterior (8.9%), lateral (8.1%) and apical (3%). The 5-year actuarial freedom from biochemical recurrence for tumors with capsular incision was worse (71.3%) than organ confined margin negative tumor (96.7%) (p <0.0001) and focal extraprostatic extension margin negative disease (89.7%) (p = 0.02), yet better than extensive extraprostatic extension margin positive tumors (58.5%) (p <0.0001). The risks of progression in men with capsular incision, focal extraprostatic extension margin positive and extensive extraprostatic extension margin negative disease were not significantly different. Risk of recurrence correlated with tumor length at the capsular incision site (p = 0.002). The 5-year risks of biochemical progression were 20.0% and 55% for less than 3 mm and 3 mm or greater of tumor cut across, respectively. CONCLUSIONS: Isolated capsular incision into tumor is uncommon in cases of radical prostatectomy performed by experienced urologists, typically Gleason score 6, and most common in the neurovascular bundle region. Isolated capsular incision has a higher recurrence rate than organ confined or focal extraprostatic extension margin negative disease, yet a lower recurrence rate than extensive extraprostatic extension margin positive tumor, and a worse prognosis with greater extent of capsular incision.

Study of prostate cancer pathologic features in Chinese populations.

OBJECTIVES: To report the pathologic features of prostate cancer and its clinical outcome in the Chinese population in Taiwan. METHODS: A total of 139 radical prostatectomy specimens removed at Koo Foundation Sun Yat-Sen Cancer Center from 1993 to 2001 were reviewed. RESULTS: The median patient age was 69 years. The histologic type was acinar adenocarcinoma in 137, mucinous adenocarcinoma in 1, and ductal adenocarcinoma in 1. The median tumor number in each prostate gland was 2. The main tumor location was distributed in peripheral zone (76.3%), followed by the transitional zone (15.1%). The Gleason score of the largest tumor was 2 to 4 in 1.5%, 5 to 6 in 7.9%, 7 in 48.9%, and 8 to 10 in 41.7%. Extraprostatic tumor extension, seminal vesicle invasion, and lymph node metastasis were found in 59.0%, 28.8%, and 13.7% of the patients, respectively. Of the 139 specimens, 56 (40.3%), 64 (46.1%), and 19 (13.7%) were pathologic Stage T2, T3, and T4, respectively. The clinical stage (P = 0.0059), serum prostate-specific antigen (PSA) level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.002), extraprostatic extension (P = 0.0012), seminal vesicle invasion (P <0.0001), and surgical margin status (P <0.0001) were all significant factors for disease progression on univariate analysis. On multivariate analysis, the serum PSA level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.03), seminal vesicle invasion (P = 0.02), and surgical margin status (P = 0.02) remained significant. CONCLUSIONS: The patients with prostate cancer cared for at the Koo Foundation Sun Yat-Sen Cancer Center were older and had greater PSA levels, a more advanced stage, higher grade tumors, and high positive surgical margin rates. Increased public awareness and implementing a PSA screening program in Taiwan are of crucial importance.