Pathology of large-caliber stereotactic biopsies in nonpalpable breast lesions.

We report the surgical pathology experience with large caliber stereotactic biopsies for non-palpable breast lesions in 217 patients. The aim is to compare the demographics to another somewhat similar center (#2), and to published results with the much smaller stereotactic needle biopsies, including our own historical controls. The large caliber tissue specimens yielded proportionally fewer nonspecific diagnoses, with remaining areas of difficulty. An evolving diagnostic strategy is outlined.

Sequence-ready contig for the 1.4-cM ductal carcinoma in situ loss of heterozygosity region on chromosome 8p22-p23.

We report the construction of an approximately 1.7-Mb sequence-ready YAC/BAC clone contig of 8p22-p23. This chromosomal region has been associated with frequent loss of heterozygosity (LOH) in breast, ovarian, prostate, head and neck, and liver cancer. We first constructed a meiotic linkage map for 8p to resolve previously reported conflicting map orders from the literature. The target region containing a putative tumor suppressor gene was defined by allelotyping 65 cases of sporadic ductal carcinoma in situ with 18 polymorphic markers from 8p. The minimal region of loss encompassed the interval between D8S520 and D8S261, and one tumor had loss of D8S550 only. We chose to begin physical mapping of this minimal LOH region by concentrating on the distal end, which includes D8S550. A fine-structure radiation hybrid map for the region that extends from D8S520 (distal) to D8S1759 (proximal) was prepared, followed by construction of a single, integrated YAC/BAC contig for the interval. The approximately 1730-kb contig consists of 13 YACs and 27 BACs. Fifty-four sequence-tagged sites (STSs) developed from BAC insert end-sequences and 11 expressed sequence tags were localized within the contig by STS content mapping. In addition, four unique cDNA clones from the region were isolated and fully sequenced. This integrated YAC/BAC resource provides the starting point for transcription mapping, genomic sequencing, and positional cloning of this region.

Endoscopic axillary lymph node dissection: an experimental study in human cadavers.

BACKGROUND: The role of axillary lymph node dissection in the staging of patients with breast carcinoma is currently under evaluation. As a result of recent advances in minimally invasive techniques, an endoscopic approach to axillary lymph node dissection may be an attractive alternative to lymphadenectomy performed via a standard "open" axillary incision. The purpose of the present study was to evaluate the technical feasibility and safety of such an approach in human cadavers. STUDY DESIGN: Twelve axillary dissections (right in seven, left in five) were performed in seven cadavers. A 2.5-cm incision was made along the lateral chest wall 12 cm inferior to the apex of the axilla. The subcutaneous axillary space was expanded with a balloon dissector, and exposure was maintained with a prototype external lift device. Endoscopic dissection was performed with three or four 5-mm ports inserted into this space. Histologic analysis was performed to document the number of lymph nodes removed. RESULTS: The mean dissection time for endoscopic axillary lymphadenectomy was 56.7+/-19 minutes (range, 30-90 minutes). Structures visualized endoscopically included the axillary vein (12 of 12 patients), the long thoracic nerve (12 of 12 patients), the thoracodorsal nerve (10 of 12 patients), and the intercostobrachial nerve (11 of 12 patients). An average of 9.9+/-7.2 lymph nodes (range, 2-22 nodes) was removed from each axilla. Open exploration of the axilla after the endoscopic dissection confirmed no injuries to any neurovascular structures. Residual lymph nodes were removed from the axilla in 7 of 12 dissections (58%; average, 4.2+/-4.0 nodes per specimen). CONCLUSIONS: These results suggest that endoscopic axillary dissection is feasible with currently available technology. Clinical trials in patients with breast carcinoma may be warranted to evaluate this technique further.

Evidence for multiple tumor suppressor genes on chromosome arm 8p in supraglottic laryngeal cancer.

Loss of heterozygosity studies of a variety of human tumors suggest that there are several tumor suppressor genes on chromosome arm 8p. To localize these genes more precisely, we utilized polymerase chain reaction amplification of microsatellite repeat polymorphisms and examined the allelic loss patterns of 17 marker loci on 8p in a population of 59 supraglottic laryngeal squamous cell carcinomas. Twenty-three of these tumors (39%) had an allelic loss at one or more of the markers examined. The allelic loss patterns of these tumors support the presence of at least three different tumor suppressor genes on 8p: one in 8p23, one in 8p22-23, and another in 8p21.

BRCA2 germline mutations in male breast cancer cases and breast cancer families.

The breast cancer susceptibility gene, BRCA2 on chromosome 13q12-13, was recently isolated. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as wall as a proportion of inherited ovarian cancer. Many BRCA2-linked families also contain cases of male breast cancer. We have analysed germline DNA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast-ovarian cancer families for mutations in BRCA2. All 17 breast-ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplified DNA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al. in this issue that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified -- all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; for thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.

Inherited breast cancer.

Five to ten percent of breast cancer is attributable to the autosomal dominant inheritance of a high-risk susceptibility gene. There are a number of known inherited cancer syndromes that confer a higher risk of breast cancer. Recently, the BRCA1 gene, which is responsible for 45% of hereditary early-onset breast cancer and for the majority of co-inheritance of breast and ovarian cancer, has been cloned. Another gene that confers an increased risk of breast cancer is the BRCA2 gene, which maps to the long arm of chromosome 13 by linkage analysis. Mutations in BRCA2 account for approximately 40% of hereditary early-onset breast cancer. In addition, at least 7% of breast cancer may occur in women who are heterozygous for mutations in a gene for ataxia-telangiectasia, an autosomal recessive chromosome instability syndrome. Predictive testing for some predisposing conditions is possible through indirect or direct mutation testing. In this article, the genetics of breast cancer are reviewed, and practical concerns for the surgeon in counseling high-risk patients are addressed.

Allelic deletion on chromosome 17p13.3 in early ovarian cancer.

Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletions extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are see only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.

A different method of hepaticojejunostomy for proximal biliary injuries.

The management of proximal biliary injuries presents a surgical challenge. Anastomoses can be difficult to perform and can have poor results. We describe a method of hepaticojejunostomy done from within the Roux-en-Y loop, which can be utilized in this situation.

Allelic loss and the progression of breast cancer.

To study genetic changes and the evolution of breast cancer, we assayed for loss of heterozygosity (LOH) in 12 sets of synchronous carcinoma in situ (CIS) and invasive cancer, compared to normal control DNA. Microsatellite markers were used, which map to each nonacrocentric autosomal arm. Eight tumor sets demonstrated LOH of the same allele in both concurrent invasive cancer and ductal CIS, for a total of 18 chromosomal loci. Three of nine tumor sets showed LOH on 11p. In two of these sets, LOH was seen on 11p only in the invasive tumor, not the corresponding CIS. One of these tumors also exhibited allelic loss in the invasive tumor for 4 loci, all of which were retained in the noninvasive tumor. For two tumor sets, LOH was mirrored in matched ductal CIS, invasive tumor, and lymph node metastasis. The maintenance of LOH for certain loci throughout the stages of breast cancer suggests clonality of the cancer cells.

Allelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q.

In order to determine which tumor suppressor loci are involved in preinvasive breast cancer, we have assayed for loss of heterozygosity (LOH) in ductal carcinoma in situ (DCIS). Areas of DCIS were microdissected from archival paraffin-embedded tissue. DNA was extracted, and LOH was determined by PCR of microsatellite markers that map to 39 autosomal arms. Either uninvolved lymph node or white cell DNA was used as normal control. A total of 61 samples of DCIS were assayed. The average number of informative tumors examined for each marker was 19 (range, 8-48). The median fractional allelic loss was 0.037. The highest percentage of LOH was shown for loci on 8p (18.7%), 13q (18%), 16q (28.6%), 17p (37.5%), and 17q (15.9%). LOH on 18q was found in 10.7% of informative tumors. Fractional allelic loss was associated with LOH on 17p, with high nuclear grade and with the comedo subtype of DCIS. LOH on 17p correlated with LOH on 17q and on 13q. Additional markers were used for 16q and 17p to determine the smallest common region of deletion. These data provide evidence that tumor suppressor loci that map to these regions are involved in the oncogenesis of breast cancer before progression to the invasive phenotype. Our findings provide additional support that multiple loci on 17p and 16q are involved in the development of breast cancer.

Pseudomyxoma retroperitonei associated with appendiceal cystadenoma.

Pseudomyxoma peritonei is a rare condition in which the peritoneal cavity is full of thick gelatinous deposits, thought to represent a tumor of varying degrees of malignancy. Most cases originate from ruptured ovarian cysts or appendiceal mucoceles, and involve the intraperitoneal cavity alone. There have only been two previously reported cases of extraperitoneal pseudomyxoma in the English literature. This report describes a case of pseudomyxoma retroperitonei arising from an appendiceal mucinous cystadenoma. The pathologic elements of the disease process, as well as treatment options, are discussed.

Midkine and pleiotrophin expression in normal and malignant breast tissue.

BACKGROUND: Some growth factors may promote tumor growth by affecting tumor angiogenesis. The angiogenic growth factor, pleiotrophin, was demonstrated previously in human breast carcinoma tissues; however, the pattern of pleiotrophin expression in normal breast tissues has not been established. METHODS: The expression of pleiotrophin and the related growth factor, midkine, was examined by polymerase chain reaction amplification of reverse transcriptase copies of RNA transcripts (RT-PCR) from freshly resected normal and malignant human breast tissues. Northern blot analysis of midkine expression was performed on a limited number of the specimens and on human and canine breast carcinoma cell lines. Clinicopathologic variables from the breast cancer patients were examined in relation to the growth factor expression patterns. RESULTS: The majority of both malignant and normal breast tissues expressed pleiotrophin. In contrast, midkine was expressed frequently in the malignant breast tissues but in only one of the normal specimens. Northern blot analysis of the breast carcinoma cells lines showed that they commonly expressed midkine transcripts. The only correlation of the growth factor expression patterns with the other clinical variables was the finding that the three midkine-negative breast carcinoma specimens also had low estrogen receptor levels. CONCLUSIONS: By this analysis, the expression of pleiotrophin was equivalent in both malignant and normal human breast tissues. Midkine, on the other hand, exhibited increased expression in the breast carcinomas but showed much lower expression in the normal breast tissue. Although the cellular source of the midkine expression was not determined by the RT-PCR assay, the Northern blot analysis showed that isolated populations of breast cancer cells commonly express this growth factor. This is the first example of a tissue simultaneously expressing high amounts of both pleiotrophin and midkine, a finding of unclear pathophysiologic significance.

Complications and outcomes in the treatment of pancreatic adenocarcinoma in the United States veteran.

BACKGROUND: Treatments for carcinomma of the pancreas have wide variations in reported complications and results. STUDY DESIGN: A population-based retrospective analysis of invasive treatments for carcinoma of the pancreas in all United States Department of Veterans Affairs hospitals was conducted using computerized patients files from 1987 to 1991. RESULTS: One thousand nine hundred sixty-four patients (99 percent male) were classified by the most aggressive treatment: 327 patients had pancreatic resections, while 1,180 had operative biliary or gastric bypasses, and 457 had percutaneous or endoscopic biliary intubations. Resection was associated with the lowest 30-day mortality rate (12 percent) and the longest mean survival period (449 days), but also the highest complication rate (37 percent) and mean period of hospitalization (53 days), with a projected five-year survival rate of 12 percent. After operative bypass, the 30-day mortality rate was 19 percent and the mean survival period was 234 days. Corresponding values after nonoperative biliary intubation were 32 percent and 223 days. Results were independent of hospital size and university affiliation, but were poorer in patients more than 60 years of age. CONCLUSIONS: This national series of therapy for carcinoma of the pancreas demonstrates that resection yielded a significantly longer survival period, with a lower mortality rate than other treatments. The results were consistent across categories of hospital size or university affiliation.

Desmoid tumor of the breast following augmentation mammaplasty.

Fewer than 100 cases of desmoid tumor of the breast have been reported. We report the first recorded case of desmoid associated with silicone gel-filled implants.

Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast.

Multiple tumor suppressor genes are implicated in the oncogenesis and progression of invasive carcinoma of the breast. To investigate the chronology of genetic changes we studied loss of heterozygosity on chromosome 17 in ductal carcinoma in situ, a preinvasive breast cancer. A microdissection technique was used to separate tumor from normal stromal cells prior to DNA extraction and loss of heterozygosity was assayed mainly using simple sequence repeat polymorphism markers and the polymerase chain reaction. Loss of heterozygosity on 17p was observed in 8 of 28 tumors (29%) when compared with normal control DNA, whereas no loss was seen on 17q, suggesting that at least one locus on 17p is involved early in the development of breast cancer.

Pseudo-tumor of the calf.

The differential diagnosis of calf swelling includes deep venous thrombosis (DVT), ruptured popliteal (Baker's ) cyst, infection, sarcoma and hematoma. Bony erosion is seldom seen in benign conditions and, when present, usually indicates tumor involvement. 'Pseudosarcoma', where hematoma may mimic sarcoma, has been described in hemophiliacs. A case is described of pseudosarcoma with bone erosion occurring as a complication of anticoagulant therapy, a clinical situation not reported previously.

Pathology and treatment of impalpable breast lesions.

With the increasing use of mammography, more needle-localized breast biopsies (NLBB) are being done. The purpose of this study was to analyze the pathology of impalpable breast lesions and the impact of NLBB on treatment strategies. From 1985 to 1990, 1,605 NLBB were performed, of which 321 (20%) were malignant. Twenty-five percent of malignant biopsies demonstrated in situ disease only. The average size of all lesions detected was 16 mm, and, for invasive cancer, 12 mm. Eighteen percent of invasive cancers had metastasized to the axillary lymph nodes. Surgical management consisted of mastectomy in 74% of patients and breast conservation treatment (BCT) in 26%. No significant difference in surgical management for women 50 years of age or younger compared with those older than 50 years of age was noted. Although the use of BCT for eligible women is recommended by the National Institutes of Health, it is not widely practiced, possibly reflecting less physician acceptance of BCT. These observations suggest that the detection of smaller, impalpable breast cancers has had no impact on treatment strategies.

Cross-femoral venous bypass in combination with tumor resection.

The cross-femoral venous bypass procedure (also known as the Palma/Dale procedure) was introduced for unilateral iliac or common femoral vein occlusions resulting in chronic deep venous insufficiency. We have utilized the procedure successfully in a patient who required extensive pelvic tumor resection involving sacrifice of pelvic venous collateral channels and unilateral ligation of external, internal, and common iliac veins. The case report and review of the literature are presented.

Sarcomatous change in a teratoma after treatment of testicular carcinoma.

Treatment can transform the metastases of nonseminomatous germ cell carcinoma into histologically mature teratoma. These lesions typically have a benign clinical course. The authors present a case of leiomyosarcoma occurring within such a lesion. It arose 18 years after therapy for metastatic embryonal carcinoma of the testis and appears to have been radiation induced.