Henry Ford Hospital medical journal最新文献

The hereditary conditions of primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2 (MEN 2) are rare clinical entities. The initial reports of two families in which the two conditions coincided have led to the identification of at least eight additional families with this clinical syndrome. In this report we describe the clinical features in five of these eight families. The salient feature in these five families is the presence of unilateral (46%) or bilateral (64%) pruritic and lichenoid skin lesions located over the upper portion of the back. Family members describe these skin lesions as intermittently intensely pruritic leading to scratching and excoriation of the upper back region. The presence of MEN 2 has been documented in 97% of family members with this skin lesion, the one exception being a child who is at risk for development of MEN 2A in whom the diagnosis has not yet been made. Of family members who have MEN 2A, 27% do not have an identifiable skin lesion, although the skin lesion developed in one patient two years after a curative thyroidectomy for medullary thyroid carcinoma (MTC). Four of the five families have members with pheochromocytoma; one with five affected members has only MTC. The finding of this clinical syndrome in geographically diverse portions of the world and the lack of overlap with MEN 2A without the skin lesion suggest it is a distinct clinical variant of MEN 2A.

We have followed a family with multiple endocrine neoplasia type 2A for 18 years. Four members have undergone total thyroidectomy for medullary thyroid carcinoma or C-cell hyperplasia, and one has required bilateral adrenalectomy for pheochromocytoma. None has developed hypercalcemic hyperparathyroidism, although parathyroid hormone levels were relatively high prethyroidectomy and fell postoperatively in the patients with high calcitonin levels. In three of the four cases, intestinal calcium absorption decreased following thyroidectomy.

Genetic linkage mapping and contig assembly using yeast artificial chromosome (YAC) technology form the basis of our strategy to clone and define the genomic structure of the pericentromeric region of chromosome 10 containing the multiple endocrine neoplasia type 2A gene. Thus far YAC walks have been initiated from five chromosome 10 pericentromeric loci including RBP3, D10S94, RET, D10Z1, and FNRB. Long range pulsed-field gel electrophoresis maps are constructed from the YACs isolated to define clone overlaps and to identify putative CpG islands. Bidirectional YAC walks are continued by rescreening the YAC library with sequence-tagged site assays developed from end-clones. Several new restriction fragment length polymorphisms and simple sequence repeat polymorphism markers have been identified from the YAC clones. In particular, two highly informative (CA)n dinucleotide repeat markers, sTCL-1 from proximal chromosome 10p (16 alleles, PIC = 0.68) and sJRH-1 from the RBP3 locus (18 alleles, PIC = 0.88), provide useful reagents for a polymerase chain reaction-based predictive genetic test that can be performed rapidly from small amounts of DNA.

Linkage analysis has been performed in four pedigrees with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (MTC) using pericentromeric chromosome 10 probes. Important information regarding carrier status has been provided in 10 individuals, many of whom would not have been identified by pentagastrin stimulation testing. We have also used pulsed field gel electrophoresis (PFGE) to link the probes H4.IRBP and pMCK2 to a 150 kb fragment. Using PFGE, no evidence was found in DNA from lymphocytes of a major DNA rearrangement in two individuals affected with MEN 2A and an individual with MEN 2B compared with normals. Metastatic MTC from one patient has been used to generate a cDNA library which will be used to screen for candidate MEN 2A and MEN 2B gene(s).

Islet cell neoplasia is a frequent occurrence in multiple endocrine neoplasia type 1 (MEN 1). Sixteen of 27 patients with MEN 1 developed functioning endocrine pancreatic tumor syndromes. Eleven of the 16 developed Zollinger-Ellison syndrome and each was evaluated by a combination of computed tomography and hepatic angiography to exclude hepatic metastasis and percutaneous transhepatic catheterization to localize the tumor. Seven of the 11 patients were found to have duodenal gastrinomas with multiple duodenal tumors in three patients. Four of the 11 patients had only pancreatic gastrinomas. In addition to the gastrinomas, other types of islet tumors in the pancreatic body or tail were found in nine of the 11 patients. None of the patients had hepatic metastases. Seven of the 11 patients were treated by distal pancreatectomy and since 1986 all patients have had duodenotomies as part of the surgical exploration. Postsurgical evaluation ranging from three months to 14 years indicates that 10 of 11 patients have normal basal gastrin levels. We conclude that duodenal gastrinomas are common in MEN 1 and can be managed successfully by appropriate operative intervention.

Megakaryoblastic termination of myeloproliferative disorders is rare. The morphology of megakaryoblastic transformation can be subtle and is often mistaken for myeloid or lymphoid proliferations. Previously reported observations suggest a relatively poor prognosis for this category of patients, making precise diagnosis imperative. A multifaceted approach using morphology, ultrastructure, cytochemistry, and immunological membrane analysis may be helpful. We present two cases of myeloproliferative disorder with aggressive megakaryoblastic phases (myelofibrosis with agnogenic myeloid metaplasia and chronic myeloid leukemia with blast crisis). The clinical course is described and the results of the morphological, cytochemical, ultrastructural, and cytogenetic studies of both cases are presented. In addition, immunochemical studies (flow cytometry) and platelet function studies (aggregation, beta-thromboglobulin, and platelet factor IV release) were done for one of these patients.

Peritoneal papillary serous carcinoma is a rare tumor that involves the surface of the pelvic and/or abdominal peritoneum. Long-term survival among patients with this tumor has been rare. Most patients with this cancer have been treated with debulking surgery and postoperative chemotherapy. A case of incompletely resected peritoneal papillary serous carcinoma with a complete response to cisplatin-based chemotherapy is reported. Subsequent laparotomy revealed no residual tumor. This case suggests that primary chemotherapy may be successful in treating unresectable primary papillary serous tumors of the peritoneum.