Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using mutiple tumour tissue microarray technique.

AIMS: To determine prostate-specific membrane antigen (PSMA) expression in normal tissues and in 3161 benign and malignant tumours and subsequently to define its sensitivity and specificity in prostatic adenocarcinoma (PaC). METHODS AND RESULTS: Multiple tissue microarray sections were stained with a monoclonal antibody to PSMA. PaC was positive in 93/141 cases (66.0%) with various staining patterns including cytoplasmic, apical, apical/cytoplasmic and cytoplasmic with membranous accentuation. Of 2174 various tumour types, 154 expressed PSMA, including 59/346 (17.0%) urothelial carcinomas of the bladder (UBC). In those tumours, the staining pattern was always cytoplasmic. All 846 benign tumours were negative for PSMA. The sensitivity and specificity of PSMA in distinguishing PaC from any other type of malignancy is 65.9% and 94.5%, respectively. Furthermore, its sensitivity and specificity in differentiating PaC from urothelial cancer is 65.9% and 82.9%, respectively. CONCLUSIONS: Despite its expression by subsets of various types of malignancies, PSMA is still considered to be fairly sensitive and highly specific for PaC.

Diagnostic utility of FLI-1 monoclonal antibody and dual-colour, break-apart probe fluorescence in situ (FISH) analysis in Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET). A comparative study with CD99 and FLI-1 polyclonal antibodies.

AIMS: To compare the sensitivity and specificity of the recently commercially available FLI-1 monoclonal (FLI-1m) antibody with the currently used antibodies [CD99 and FLI-1 polyclonal (FLI-1p)] in the diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and to determine the diagnostic value of the EWSR1 (22q12) dual-colour, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique. MATERIALS AND METHODS: Forty-three cases of well-documented EWS/PNET and 15 non-EWS/PNET cases were retrieved from the archival files. Immunohistochemistry (IHC) for FLI-1p, FLI-1m and FISH analysis was performed. RESULTS: The most sensitive and specific test panel for the diagnosis of EWS/PNET is the combination of CD99 and FLI-1p. FISH had a very high specificity (100%) but only a moderate sensitivity (50%). CONCLUSION: The combination of CD99 and FLI-1p is the method of choice for the diagnosis of EWS/PNET. EWRS1 (22q12) dual-colour, break-apart rearrangement probe FISH should be used as a confirmatory test in addition to CD99 and FLI1-p due to its high specificity.

Demonstration of urokinase expression in cancer cells of colon adenocarcinomas by immunohistochemistry and in situ hybridization.

The question whether urokinase is expressed in human colon cancer by the cancer cells themselves or by surrounding stromal elements such as fibroblasts, macrophages, and leukocytes, which transfer the activator to the receptors of the cancer cells, has been a controversial one. In the present study 12 cases of colorectal cancer were investigated by immunohistochemical methods using three monoclonal antibodies of different specificity against urokinase. Cytoplasmic staining of strongly varying intensity was observed in all cases, with the antigen expressed most strongly in the apical and the basal regions of the cancer cells. In some cases, staining was also found in stromal elements surrounding the cancer glands. That the activator was indeed the product of the cancer cells was demonstrated by in situ hybridization using a uPA-cDNA probe, which detected the presence of uPA-mRNA in both the basal and the apical regions of the cancer cells. A monoclonal antibody against the receptor for uPA showed similar localization. These findings indicate that the activator is expressed by the cancer cells and is not recruited by them from stromal elements.

Clinicopathologic effects of cryotherapy on hepatic vessels and bile ducts in a porcine model.

BACKGROUND: The proximity of a hepatic tumor to major vessels and bile ducts limits the use of cryotherapy because of the potential damage to these structures. However, the effects of cryotherapy on major hepatic vessels and bile ducts are not well understood. METHODS: Nine pigs underwent laparotomy and intraoperative ultrasound to identify hepatic vessels larger than 5.0 mm. Cryotherapy consisting of two freeze-thaw cycles was performed, incorporating the identified vessel. In four pigs the Pringle maneuver was performed to determine the effects of partial vascular occlusion on the hepatic parenchyma and structures undergoing cryotherapy. The animals were sacrificed 30 days postoperatively, and the livers were processed for histologic examination. RESULTS: Eight of the nine livers had vessels larger than 5.0 mm incorporated into the iceball, with all vessels having evidence of infarction but remaining patent. All the livers had major bile ducts incorporated in the iceball, with eight having evidence of infarction. The Pringle maneuver had no real effect on the degree of vessel and bile duct infarction. There was no incidence of hepatic bleeding, liver fracture, bile leak, or hemobilia. CONCLUSIONS: Cryotherapy results in the infarction of major hepatic vessels and bile ducts but can be safely performed in the porcine model. Proximity of tumors to major vascular and biliary structures may not be a contraindication to the use of cryotherapy. Further studies are necessary to determine whether cryotherapy can be used in humans.

Papillary carcinoma of the thyroid metastatic to the parapharyngeal space.

The parapharyngeal space is a complex anatomic area which can give rise to a variety of both primary and metastatic neoplasms. Squamous cell carcinoma can also present as a parapharyngeal space mass, either by direct extension or by metastases. Occult thyroid carcinoma presenting as a parapharyngeal space mass is a rare clinical occurrence which has been only sporadically reported in the medical literature. We present a case of occult papillary thyroid cancer with parapharyngeal space metastasis in the form of an isolated tumor, as well as a review of the literature on similar presentations. This rare situation has been previously described only once in the medical literature. Metastatic thyroid cancer should be considered in the differential diagnosis of a parapharyngeal space mass.

Utility of mapping lymph nodes cleared from rectal adenocarcinoma specimens.

The lymph node clearing technique improves the detection of lymph nodes in colorectal cancer specimens. The purpose of this study was to determine the utility of mapping the lymph nodes cleared from rectal adenocarcinoma specimens by evaluating the possible relationship between the pattern of lymph node metastases to the site of the recurrent disease. A retrospective medical record review was performed in 40 patients with primary rectal adenocarcinoma. The specimens were analysed by lymph node clearing technique and mapped after surgery. The lymph nodes were mapped according to their location in the cleared specimens. Statistical analysis was performed using the chi 2-test. A total of 1290 lymph nodes were cleared in 40 specimens. Of these, 1126 (87%) lymph nodes were < or = 5 mm. One-hundred and ten (9%) lymph nodes were metastatic. Sixty-seven (61%) of these 110 lymph nodes were 5 mm or less in size. The majority of lymph nodes with or without metastases were in the pelvis, as opposed to an extrapelvic location (P = 0.0001). Eleven patients recurred. In nine of these patients the recurrence showed a direct relationship between the level of metastatic lymph node location (pelvic vs. extrapelvic) and the site of the recurrent disease (loco-regional or systemic, P = 0.05). The majority of lymph nodes, both normal and metastatic, cleared from specimens from rectal adenocarcinoma were < or = 5 mm in diameter. The lymph node mapping technique may help in predicting the site of recurrence.

Clinical significance of colorectal cancer: metastases in lymph nodes < 5 mm in size.

BACKGROUND: The clinical significance of metastases in small lymph nodes is not known. Our objective was to evaluate possible relationships between the number and size of lymph node metastases and survival after potentially curative colorectal resection. METHODS: A retrospective chart review was performed in patients with Dukes'C (any T, N(1-3') M0) colorectal cancers from July 31, 1971 to December 31, 1987. All specimens underwent the lymph node clearing technique. Statistical analysis was performed with the log rank test and the Cox proportional hazards model. RESULTS: In 77 patients there were 253 (8%) of 3,087 cleared lymph nodes with metastases. One hundred seventy-five (69%) of these metastatic nodes were 5 mm or less in diameter. The distal margin of resection (p = 0.011) and number of positive lymph nodes (p = 0.036) were statistically significant factors influencing overall survival. There was no significant difference in overall survival (p = 0.73) or disease-free survival (p = 0.56) whether the involved lymph nodes were < or > 5 mm in size. CONCLUSION: Most metastatic lymph nodes were < 5 mm in diameter. Based on our results, the size of lymph node metastases do not affect disease-free or overall survival in colorectal carcinoma.

Cellular proliferative activity of mammographic normal dense and fatty tissue determined by DNA S phase percentage.

A prospective study was undertaken to evaluate associations among mammographic normal dense and fatty tissue, benign histologic findings, and cellular proliferative activity determined by DNA S phase percentages. Mammographic and histologic findings of benign, normal dense and fatty tissue contained in 100 excised specimens were cross-tabulated with flow cytometric DNA S phase percentages of needle aspirates obtained under radiographic guidance. Histologic evidence of atypia or hyperplasia was present in 21 (32%) of 66 fatty tissue samples and 11 (32%) of 34 dense tissue samples (p = NS). The median S phase percentages were identical for mammographic fatty and dense tissue (median % S phase = 5.35). The frequency of high S phase percentages (above the median) was not significantly different for tissue containing atypia or hyperplasia, 47% (15 of 32), as compared to tissue containing other benign histology, 52% (35 of 68) (p = NS). These frequencies were similar in women 49 and younger or 50 and older. These data show that mammographic normal dense and fatty tissues contain similar frequencies of histologic atypia or hyperplasia and low and high cellular proliferative activity determined by DNA S phase percentages in women aged 49 and younger and 50 and older.

Curative resection for stage I rectal cancer: natural history, prognostic factors, and recurrence patterns.

Our goal was to evaluate the recurrence patterns and outcomes of a large group of patients with stage I rectal adenocarcinoma treated at a single institution with uniform surgical and pathological techniques. Medical records of 71 patients who had undergone potentially curative surgery were reviewed to determine clinical and histologically significant prognostic factors that could affect survival and recurrence patterns. The median follow-up for all patients was 81 months. Twenty patients had T1N0M0 cancers and 51 patients had T2N0M0 cancers. The median number of lymph nodes examined per surgical specimen was 32. There were no recurrences in the 20 patients with T1 lesions. All 7 recurrences (10%) occurred in patients with T2 lesions. Only 2 of these recurrences were local. In the T2 group, the 5- and 10-year disease-free survivals were 88% and 83%, respectively. The 5- and 10-year disease-free survival for all state I lesions was 91% and 88%, respectively. The overall recurrence rate of 10% does not justify adjuvant therapy for stage I rectal adenocarcinoma. Although the subset of patients with T2N0M0 distal one-third rectal cancers may be at risk for recurrence, additional prognostic factors are needed to evaluate these patients before adjuvant therapy can be recommended.

Malignant melanoma of the gallbladder: report of a case and review of the literature.

A case of primary melanoma of the gallbladder is presented and review of the literature. Eighteen cases have been previously reported. The diagnosis is usually not made preoperatively. Metastatic melanoma to the gallbladder as an isolated site is also rare.

Intraoperative small bowel enteroscopy in familial adenomatous and familial juvenile polyposis.

BACKGROUND: In familial adenomatous polyposis and juvenile polyposis, polyps can occur throughout the gastrointestinal tract. METHODS: We report seven patients with familial adenomatous polyposis and two patients with juvenile polyposis who underwent small bowel enteroscopy at the time of exploratory celiotomy either for colectomy or other pathology. RESULTS: Polyps in the jejunum and/or ileum were noted in five of nine (56%) patients at enteroscopy. In three of nine (33%) patients these polys were adenomatous. Two of these patients had polyps in the jejunum and in the ileum, whereas one patient had jejunal adenomas alone. These polyps were from 3 mm to 30 mm in size. The remaining two patients with polyps had lymphoid hyperplasia in the ileum. All three patients who had adenomas at intraoperative small bowel enteroscopy had duodenal adenomas at esophagogastroduodenoscopy. At the age of 14 years, one patient had an intramucosal carcinoma in a small bowel juvenile polyp. CONCLUSION: Baseline small bowel enteroscopy should be considered at the time of surgical exploration in patients with asymptomatic familial adenomatous polyposis and juvenile polyposis. In patients with duodenal polyps, enteroscopy should be performed at the time of surgery. Biopsy and/or excision of larger polyps should be performed because these polyps may harbor a carcinoma.

In situ breast carcinoma after treatment during adolescence for thyroid cancer with radioiodine.

We reviewed the courses of patients treated during childhood or adolescence for thyroid cancer to estimate the frequency of, and to identify possible risk factors for, the occurrence of second malignant tumors in this population. We identified all patients treated for thyroid cancer in a cohort of 1,406 pediatric cancer patients who were diagnosed prior to 20 years of age during the period January 1, 1960 through December 31, 1988 and who were treated at Roswell Park Cancer Institute. Twelve patients were treated for thyroid cancer, of whom nine were women. In situ breast carcinoma was diagnosed 25 and 26 years after diagnosis of thyroid cancer in two of four women treated with radioiodine. No new cancers were diagnosed in the five women treated with thyroidectomy only. Two of four women treated for thyroid cancer during adolescence with radioiodine, which is concentrated in the breast as well as other organs, developed in situ breast carcinoma. Review of a large cohort of adolescent female thyroid cancer patients treated with radioiodine is necessary to provide an accurate estimate of their risk of developing breast cancer. These patients must remain under medical surveillance throughout their lifetimes to facilitate prompt diagnosis of and early intervention for new conditions, such as the occurrence of breast cancer.

Prognosis and recurrence patterns of anal adenocarcinoma.

BACKGROUND: Anal adenocarcinomas are rare cancers, constituting fewer than 10% of all anal cancers. This is a retrospective review of 10 patients with anal adenocarcinoma. PATIENTS AND METHODS: Seven men and 3 women with a median age of 59 years (range 38 to 82) participated in the study. Using the 1976 World Health Organization classification, 4 patients had the rectal type of cancer, 2 had the anal duct type, and 1 had the anorectal fistula type. The 3 remaining patients had unclassifiable tumors with solely extramucosal disease. Seven patients underwent abdominoperineal resection, 1 had a radical vulvectomy and proctectomy, and 2 had local excision. RESULTS: The median survival was 29 months (range 5 to 249). Seven patients developed a recurrence at the following sites: 2 perineal, 5 inguinal, and 5 distant metastases. Five patients died from their disease a median of 28 months after surgery, and 2 patients died of unrelated causes. Three patients are alive at a median of 54 months; 2 of these patients are free of disease and 1 has a perineal recurrence. CONCLUSION: Anal adenocarcinomas were found to be a rare, heterogeneous group of tumors with a poor prognosis despite radical surgery.

Lobular carcinoma in situ: observation without surgery as an appropriate therapy.

BACKGROUND: The finding of lobular carcinoma in situ (LCIS) in the breast has generally prompted treatment with unilateral or bilateral mastectomy. Most experts now feel that LCIS simply identifies a woman who is at high risk to develop future breast cancer and requires only close clinical and mammographic follow-up. This approach has been recommended at our institution for > 15 years. This study defines the natural history of a population of women with LCIS who were treated by observation alone. METHODS: Women with a pathologic diagnosis of LCIS were identified by tumor registry search. Records and pathology were reviewed. Radiographic-pathologic correlation was performed on women who had undergone mammographic-localized breast biopsies. One hundred forty-nine women with LCIS were identified. Eighty four were excluded from analysis because of synchronous invasive cancer or ductal carcinoma in situ (DCIS). The remaining 65 women formed the basis of this report. RESULTS: Sixty-five women with LCIS were treated from 1963 through 1990. Median follow-up was 83 months. No women were lost to follow-up. Median age at diagnosis was 48 years (range 37-81), and 32% had a family history of breast cancer. Clinical findings leading to biopsy were breast mass in 43, nipple discharge in three, and mammographic abnormality in 19. Mammographic-pathologic correlation showed that the focus of LCIS in these 19 women was not associated with the mammographic abnormality. Fourteen of 65 women underwent mastectomy after diagnosis of LCIS (nine ipsilateral, five bilateral). Fifty-one of 65 women elected observation alone. In the observation group, 13 of 51 women (25%) underwent a second breast biopsy for a clinical or mammographic abnormality during the follow-up period. The median interval to biopsy was 50 months. Pathology was benign in two, LCIS in seven, DCIS in one, and invasive cancer in three. All seven women with LCIS on subsequent biopsy continued with observation and none developed breast cancer. All four cancers were detected by mammography without an associated palpable mass. Three of four cancer masses were < 1 cm in diameter. The woman with DCIS was 47 years of age and developed DCIS 106 months after LCIS diagnosis. She was treated by total mastectomy and is disease free 108 months later. The three women with invasive cancer developed this at 41, 53, and 69 months after diagnosis of LCIS. All were < 50 years of age. All three cancers were in the same breast as the previous LCIS. Two women were treated by modified radical mastectomy, and the third had wide excision/axillary dissection followed by radiation therapy. They are alive and disease-free at 16, 82, and 116 months. CONCLUSIONS: Four of 51 women treated with observation alone after diagnosis of LCIS developed breast cancer. All were detected by screening at an early stage. LCIS appeared to be an incidental finding on biopsy of mammographic abnormalities. The policy of observation alone for the finding of LCIS spares women mastectomy. Furthermore, cancers that develop in follow-up are likely to be detected at an early stage and be amenable to curative therapy. Observation alone is appropriate treatment for women with LCIS.

Atypical hyperplasia: frequency and mammographic and pathologic relationships in excisional biopsies guided with mammography and clinical examination.

PURPOSE: To ascertain the frequency and pathologic relationships of atypical hyperplasia in biopsy specimens obtained after clinical and mammographic examination. MATERIALS AND METHODS: Clinical, mammographic, and histologic findings were prospectively correlated in 300 consecutive excisional biopsies. RESULTS: Atypical hyperplasia was detected in 26 (17%) of 154 biopsies with benign findings and 19 (13%) of 146 biopsies with malignant findings overall (P > .05). The frequency of atypical hyperplasia was only 4% (two of 55 specimens) in clinically prompted biopsies with benign findings but 24% (24 of 99 specimens) in mammographically prompted biopsies with benign findings (P = .002), increasing to 31% (21 of 68 specimens) in benign microcalcifications and 40% (18 of 45 specimens) in benign microcalcifications associated with adenosis. Atypical hyperplasia was found most often within (16 [62%] of 26 cases) or adjacent to (nine [35%] of 26 cases) another lesion that prompted biopsy. CONCLUSION: Most atypical hyperplasia is not a random finding in benign biopsy specimens but shows a statistically significantly greater frequency in association with microcalcifications detected with mammography only, especially those in areas of adenosis.

Endocrine organ metastases in subjects with lobular carcinoma of the breast.

OBJECTIVE: To define the frequency and pattern of endocrine organ metastases in patients dying of invasive lobular carcinoma. DESIGN: Postmortem microscopic evaluation of the ovaries and adrenal, pituitary, thyroid, and parathyroid glands for breast cancer metastases. SETTING: Roswell Park Cancer Institute, Buffalo, NY, between 1971 and 1990. SUBJECTS: One hundred eighteen subjects who died of their cancer: 86 had infiltrating ductal carcinoma; 32, invasive lobular carcinoma. MEAN OUTCOME MEASURE: Quantitative measurements to allow frequency determinations and statistical comparisons. RESULTS: Endocrine organ metastases were found in 91% of the subjects with invasive lobular carcinoma vs 58% of subjects with infiltrating ductal carcinoma. The adrenal gland was most frequently involved. Multiple endocrine metastases were most common in the group with invasive lobular carcinoma. CONCLUSIONS: A relationship exists between invasive lobular carcinoma and endocrine metastases. This indicates that antemortem endocrine evaluation may subsequently improve quality-of-life treatment.

Evaluation of porfimer sodium fluorescence for measuring tissue transformation.

BACKGROUND: Neoplastic tissue can be detected by its increased fluorescence compared with surrounding normal tissue after the injection of the tumor-localizing compound porfimer sodium (Photofrin; Quadra Logic Technologies, Vancouver, BC, Canada). In vivo fluorescence photometry is a nonimaging photodetector technique that detects specific 690 nm fluorescence of the porphyrin by subtracting nonspecific 612 nm excitation from 630 nm excitation. The technique was applied in the developmental stages of the 9,10 dimethyl-1,2-benzanthracene (DMBA)-induced hamster buccal cheek pouch carcinoma model to (1) quantitate and characterize porfimer sodium fluorescence and uptake as it relates to lesion progression and biochemical changes and (2) determine whether porfimer sodium-induced fluorescence will vary with promotional and inhibitory stimuli. METHODS: Groups of Syrian Golden hamsters had their cheek pouch buccal mucosa exposed to a 0.5% DMBA in acetone three times per week for 6 weeks (premalignant lesions), 12 weeks (squamous cell carcinomas), or other specified durations. The rate of malignant transformation was either promoted (by either carbon dioxide laser incision or continued DMBA application) or inhibited (by the administration of either somatostatin analogue RC-160 [D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2] or bombesin antagonist RC-3095 [D-Tpi-Gln-Trp-Ala-Val-Gly-His-Leu psi (CH2NH)Leu-NH2]). Groups of DMBA-exposed hamsters were subsequently injected with 1.0 mg/kg of porfimer sodium during the various stages of tumor development. Twenty-four hours after injection, fluorescence levels were measured by in vivo fluorescence photometry. Samples of tumors, dysplastic mucosal tissue, and normal-appearing oral mucosa were biopsied and used for either tissue extraction assays, histopathologic examination, or tyrosine kinase activity assay as an index of rate of transformation. RESULTS: Results demonstrated that porfimer sodium is retained in DMBA-treated tissue. Fluorescence is completely accounted for by porfimer sodium uptake. The duration of exposure to carcinogen is proportional to porfimer sodium fluorescence. This relationship establishes that premalignant lesions can be distinguished from normal tissue by porfimer sodium uptake and fluorescence. The changes in increased tyrosine kinase activity paralleled the increase in porfimer sodium fluorescence. Alterations in the rate of tissue transformation produced equivalent alterations in porfimer sodium-induced fluorescence. CONCLUSIONS: These results suggest that porfimer sodium uptake and fluorescence can be used in a prognostic manner to diagnose and determine the course of transformation of individual lesions.

Results of salvage mastectomy for local recurrence after breast-conserving surgery without radiation therapy.

BACKGROUND: Between 1975 and 1987, 128 patients with infiltrating breast cancer, categorized as clinical Stage I and II disease, were treated by breast conservation surgery without radiation therapy. MATERIALS: After a median disease-free interval of 20 months (range, 8-64 months), 25 of 128 patients had local recurrence, for which salvage mastectomy was performed. The results of modified radial mastectomy as a salvage procedure were analyzed in these 25 patients. RESULTS: After a median disease-free interval of 52 months (range, 8-75 years) after the salvage procedure, 12 patients had chest wall and distant recurrences, whereas 13 patients remained free of disease. The 5-year actuarial disease-free and overall survival rates after the salvage mastectomy were 51% and 65%, respectively. CONCLUSIONS: Univariate analyses of factors affecting disease-free survival and overall survival showed that the size of the local recurrence (< or = 2 cm) (P = 0.009) and the number of pathologically positive axillary nodes at the time of the salvage procedure (fewer than four nodes) (P = 0.002) were associated with a better prognosis.

Patterns of occurrence of second primary non-mammary malignancies in breast cancer patients: results from 1382 consecutive autopsies.

An autopsy series on the patterns of occurrence of second primary non-mammary malignancies (SPNM) in breast cancer patients is presented. SPNM occurred in 11.4% of breast cancer patients at a mean interval of 83.9 months. Seventy-five per cent of them occurred by the first decade following breast cancer. The most common system of SPNM occurrence was the female genital system, followed by the gastrointestinal system. The single organs most commonly involved were the colon and rectum, ovary and uterine cervix. There was no evident association between administration of radiotherapy or chemotherapy for the breast cancer and the risk for SPNM development except in the case of post-radiation sarcomas at or near the site of post-mastectomy radiotherapy. Death was caused by the breast cancer in 28.7% of patients and by the SPNM in 53.5%. In 10.6% of the cases the SPNM was clinically interpreted as metastatic breast cancer until autopsy.