Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups.

BACKGROUND: Despite significant differences in age of onset and incidence of breast cancer between Caucasian (CA), African-American (AA) and Korean (KO) women, little is known about differences in BRCA1/2 mutations in these populations. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations and the association between BRCA1/2 mutation status and secondary malignancies among young women with breast cancer in these three racially diverse groups. METHODS: Patients presenting to our breast cancer follow-up clinics selected solely on having a known breast cancer diagnosis at a young age (YBC defined as age <45 years at diagnosis) were invited to participate in this study. A total of 333 eligible women, 166 CA, 66 AA and 101 KO underwent complete sequencing of BRCA1/2 genes. Family history (FH) was classified as negative, moderate or strong. BRCA1/2 status was classified as wild type (WT), variant of uncertain significance (VUS) or deleterious (DEL). RESULTS: DEL across these three racially diverse populations of YBC were nearly identical: CA 17%, AA 14% and KO 14%. The type of DEL differed with AA having more frequent mutations in BRCA2, compared with CA and KO. VUS were predominantly in BRCA2 and AA had markedly higher frequency of VUS (38%) compared with CA (10%) and KO (12%). At 10-year follow-up from the time of initial diagnosis of breast cancer, the risk of secondary malignancies was similar among WT (14%) and VUS (16%), but markedly higher among DEL (39%). CONCLUSIONS: In these YBC, the frequency of DEL in BRCA1/2 is remarkably similar among the racially diverse groups at 14%-17%. VUS is more common in AA, but aligns closely with WT in risk of second cancers, age of onset and FH.

Treatment of hepatic metastases from colorectal origin.

Currently, chemotherapy for hepatic metastatic disease is palliative at best. However, successful resection of hepatic metastatic deposits from colorectal origin demonstrates a five-year survival, approaching 60 percent in selected cases.

Bladder involvement in metastatic breast carcinoma.

The literature concerning the uncommon findings of bladder involvement of breast carcinoma is suggestive of a recent increase in reported cases. We report on 3 additional women with vesical deposits of metastatic breast carcinoma. The clinical presentation and dire significance of such cases, and their relationship to progesterone and estrogen receptor expression are discussed. We also postulate on the possible increase in the numbers of reported cases.

Metastatic colon carcinoma to the jaw: a case report and review of the literature.

Presented is a case of adenocarcinoma of the cecum metastatic to the anterior mandible. The patient had a Duke's C2 cecal adenocarcinoma resected twenty months prior to her development of loose teeth, jaw pain, and jaw mass. A biopsy of the mass revealed metastatic adenocarcinoma, identical to her primary neoplasm. Metastatic carcinoma to the mandible is a rare event. A review of the literature reveals only nineteen cases of colon carcinoma metastatic to the jaw. When further subdivided, there is only one other case of cecal adenocarcinoma metastasizing to the jaw. Almost half of the other cases have been rectal carcinomas. Treatment of these patients has been uniformly unsuccessful, with life expectancy reported between one and seven months. The literature has shown that 5-FU and radiotherapy may produce palliation of symptoms. The patient presented here responded well to 5-FU and radiotherapy.

Association of inflammatory bowel disease (IBD) with indolent soft-tissue sarcomas: report of two cases and review of literature.

Two patients with inflammatory bowel disease (IBD) and indolent forms of soft-tissue sarcomas (extraosseous osteogenic sarcoma and desmoid tumor) are presented. The literature is reviewed regarding these tumors, which have not previously been recognized in association with IBD. Despite the well-established relationship between IBD and neoplasms of epithelial and lymphoreticular origin, there have been limited data in this context pertaining to mesenchymal tumors. Two preceding reports have described the coexistence of IBD with another form of soft tissue sarcoma (Kaposi's sarcoma). Given that this relationship has now been observed in four cases, the possibility that soft-tissue sarcoma and IBD do not coexist fortuitously must be considered. This suggestion is raised in light of the rare incidence of these disorders, the limited understanding of factors governing their expression, and the known association of IBD with other forms of neoplasia.

Essential thrombocytosis with the Philadelphia chromosome (Ph').

Essential thrombocytosis is a myeloproliferative disease not known to have consistent cytogenetic abnormalities. A 46-year-old black woman with essential thrombocytosis and a Philadelphia chromosome is reported. Iron deficiency and tuberculosis were present but when effectively treated did not result in resolution of thrombocytosis. Megakaryocytic hyperplasia of bone marrow, abnormal platelet function studies and a compatible clinical state suggested the diagnosis of essential thrombocytosis. The diagnostic criteria for other myeloproliferative diseases were not met. The Philadelphia chromosome was consistently obtained from bone marrow preparations. We conclude that the Philadelphia chromosome may be found in essential thrombocytosis as well as other, previously reported, myeloproliferative diseases.

New options for central venous access in cancer chemotherapy. Multiple lumen catheters.

New technology has allowed the creation of single catheters with up to four separate luminal channels for access to the central venous system. Since cancer chemotherapy may be associated with local complications specifically related to the mode of intravenous administration, temporary central venous access with a multiple lumen catheter (MLC) offers distinct theoretical advantages over previously used peripheral venous sites. As part of a prospective study to evaluate the clinical efficacy of MLC, the authors have separately studied the usefulness of these catheters in providing venous access to patients receiving chemotherapy.

Paraplegia following intrathecal chemotherapy: neuropathologic findings and elevation of myelin basic protein.

An 11-year-old boy developed a severe myelopathy after an eight-year history of acute lymphoblastic leukemia and numerous courses of intrathecal chemotherapy. Myelin basic protein in the cerebrospinal fluid (CSF) was elevated. Neuropathologic examination disclosed extensive microvacuolar changes in the white matter of the spinal cord. The pathogenesis of myelopathy following intrathecal chemotherapy administered by lumbar puncture includes an early effect on the myelin sheath. Serial assessment of CSF myelin basic protein levels in patients receiving intrathecal chemotherapy may be useful in the early diagnosis of this disorder.

Familial erythroleukemia: four cases of the Diguglielmo syndrome in close relatives.

Erythroleukemia was diagnosed in three brothers during a 6-month period in 1976. A son of one leukemic had died 5 years earlier with erythroleukemia. First-degree relatives of these men were evaluated in an attempt to identify contributing factors. Twenty-four relatives have been studied. Immunoglobulin M was elevated in 14 of 16 persons (mean, 352.8 mg/dl; normal, less than 145 mg/dl; P less than .001). This was neither a monoclonal protein nor rheumatoid factor. Age-dependent red cell enzymes were increased. Erythrocyte hexokinase was markedly increased in 23 of 24 persons (mean, 35.05 units/100 ml RBC; normal, less than 18 units; P less than .001). Evidence for a hemolytic state was absent. Bone marrow samples in 8 first-degree relatives were normal. Cytogenetics were normal in 18 relatives. One leukemic exhibited hypoploidy and a marker chromosome. The association of an immunoglobulin abnormality and enzymopathy in the leukemics and relatives alike suggests a hereditary susceptibility to the development of erythroleukemia. The exact link is not identified.

Carcinoma with unknown primary tumor (CUP syndrome).

Approximately 10% of adenocarcinomas are first seen without a detectable primary tumor. The clinical state that results when a metastatic deposit is more symptomatic than its primary I have termed the CUP (carcinoma unknown primary) syndrome. By definition CUP tumors are incurable by current treatment but their management often includes extensive and expensive efforts to detect the organ of origin. This article stresses the pitfalls in clinical diagnosis and management and outlines an empiric, palliative approach to therapy.

Bilateral internuclear ophthalmoplegia after intrathecal chemotherapy and cranial irradiation.

A 26-year-old man developed transient bilateral internuclear ophthalmoplegia with exotropia after cranial irradiation and intrathecal administration of methotrexate for lymphoma. Resolution of the ophthalmoplegia and the decrease in abnormally high levels of cerebrospinal fluid myelin basic protein after discontinuation of intrathecal medication suggested demyelination from chemotherapy and irradiation.