Gorlin syndrome associated with midline nasal dermoid cyst.

Gorlin syndrome is an autosomal dominant multisystem disorder characterised by multiple basal cell naevi, cysts of the jaw, pits of the palms and soles, skeletal anomalies, and various other defects. Patients with Gorlin syndrome have a predisposition to basal cell carcinomas and other neoplasms. This is the first report to describe the coexistence of Gorlin syndrome and a nasal dermoid cyst. A 4 year old girl was diagnosed with medulloblastoma and treated with surgery and radiation therapy. A genetic evaluation was sought because of the brain tumour, multiple small naevi localised mostly on the upper torso, and rib abnormalities. Biopsies of several naevi showed naevoid basal cell carcinoma. Past medical history was significant for a midline nasal punctum noted at birth. The significance of this finding was unrecognised until the dermoid cyst enlarged, just before the diagnosis of her brain tumour. A common tissue of origin exists between basal cell naevi, cysts of the jaw, and dermoid cysts. We propose that the association of these two rare conditions in one patient is not a chance occurrence.     

Liver abnormality in ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a potentially fatal condition associated with the therapeutic induction of ovulation in infertility. Liver function abnormality has been previously reported in four patients, one of whom had ultrastructural abnormalities on liver biopsy. This paper describes a patient presenting with severe OHSS 16 days after ovulation had been induced. Liver function abnormality was apparent 11 days later, with a sustained rise in alkaline phosphatase and aspartate aminotransferase (AST) which lasted up to 2 months. A liver biopsy performed during the second month of her protracted hospital admission showed marked zonal fatty change (acinar zone 1) and associated inflammation, with mitochondrial crystalline inclusions and rough endoplasmic reticulum dilatation on electron microscopy. This report discusses the clinical features and possible aetiological factors.     

Canine ovarian fibroma associated with prolonged exposure to mibolerone

A study to determine the efficacy and safety of mibolerone following prolonged oral administration in the female dog was terminated after 9.6 yr. Histopathologic examination revealed the presence of small dense tumors in the ovaries of 12 of 92 dogs given mibolerone at the approximate efficacious dose. No such tumors were found in 60 vehicle control animals or 55 animals given exaggerated doses of mibolerone. The tumors were composed of dense fibrous connective tissue and incorporated occasional ovarian medullary tubules. The tumors appeared to grow by expansion with no evidence of invasion or metastasis and were diagnosed as fibromas.     

Conservative treatment of recurrent ovarian fibromas in a young patient affected by Gorlin syndrome

The case of recurrent bilateral ovarian fibromas occurring in a 22 year old Italian girl affected by Gorlin syndrome is reported. Ovarian fibromas occur in 75% of female patients with Gorlin syndrome and their recurrence has rarely been reported in the literature. Management is guided by the benign nature of the lesion and consists of surgical removal of the fibroma. Preservation of the normal ovarian tissue is recommended even though there is risk of recurrence of the fibroma.     

Non-nuchal-type fibroma associated with Gardner's syndrome. A hitherto-unreported mesenchymal tumor different from fibromatosis and nuchal-type fibroma

We describe a unique benign mesenchymal tumor in paraspinal location in a 13-year-old patient with Gardner's syndrome. The Gardner's syndrome in this patient consisted of multiple (more than 100) polyps throughout the entire colon with most in the cecum and rectum, three osteomas in the frontal area of the skull and one in the third right rib, and multiple superficial skin tumors. One of these cutaneous tumors was excised and histologically diagnosed as an epidermal cyst. Both father and uncle of this patient suffered from Gardner's syndrome as well. Microscopically the mesenchymal tumor was histologically different from nuchal type fibroma and fibromatosis. It consisted of a diffusely-growing fibrous mass composed of dense collagenous fibers and relatively numerous, bland-looking, spindle-shaped cells. The collagen fibers had haphazard spacing with no lobular arrangement. The collagen fibers were of a very coarse quality. No entrapment of adipose tissue, skeletal muscle or peripheral nerves was seen in the lesion. Immunohistochemically the tumor was vimentin positive and smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin and desmin negative.     

Gorlin syndrome with ulcerative colitis in a Japanese girl

We present the case of a 14-year-old Japanese girl who had both Gorlin syndrome and ulcerative colitis. She had complained of blood stools for 6 months and severe scoliosis from her infancy. Physical examination revealed multiple nevi, palmar and plantar pits, jaw cysts, and calcification of the falx cerebri, leading to the diagnosis of Gorlin syndrome. Total colonoscopy revealed an edematous and spotty bleeding mucosa extending from the anus to the transverse colon. Histological examination was also compatible with ulcerative colitis. Thus, we diagnosed her as having Gorlin syndrome with ulcerative colitis. Gene analysis revealed a mutation, 1247InsT, in the human patched gene (PTCH), resulting in the truncation of PTCH protein. Since Gorlin syndrome and ulcerative colitis are rare disorders in childhood, this association is interesting, suggesting a correlation between the hedgehog signaling and intestinal disorders.     

Major karyotypic abnormality in a child born to a woman with untreated malignant melanoma

The karyotype of a 7-month-old child had 46 chromosomes, including five abnormal chromosomes in cultured lymphocytes. G-banding indicated the presence of reciprocal translocation products between chromosomes 1 and 7 and between chromosomes 4 and 15. A probable third translocation involved the same chromosome 4p arm and 12q. All meta-phases showed these changes. C-band markers and the presence of reciprocal exchange products indicated that the chromosome changes occurred in the zygote or a post-zygotic cell of the child. The mother developed malignant melanoma while carrying the child but did not receive therapy before its birth. The suggestion is made that an undetected common agent was involved in the aetiology of the mother's tumour and the clastogenic change to the child's chromosomes.     

Clonal karyotypic evolution in an embryonal rhabdomyosarcoma with trisomy 8 as the primary chromosomal abnormality

An embryonal rhabdomyosarcoma was analyzed cytogenetically. In primary cultures fed a serum-containing medium, 11 clones with karyotypic abnormalities were found. One had trisomy 8 only. The other 10 clones had trisomy 8 as well as additional evolutionary changes that included trisomy for part or all of chromosome 2, isochromosomes for the short and long arms of chromosome 11, isochromosomes for the long arm of chromosome 8, and extra copies of chromosome 8, some of which had an interstitial deletion in 8q. In those primary cultures that had grown in a chemically defined, serum-free medium and in all passaged cultures, trisomy 8 was the only aberration. Our findings and a survey of published information point to gain of one chromosome 8 as a frequent primary karyotypic abnormality in embryonal rhabdomyosarcomas. Trisomy for part or all of chromosomes 2 and 11 and additional gains of chromosome 8 material seem to be common secondary changes. © 1993 Wiley-Liss, Inc.     

Deletion of Xq23 is a recurrent karyotypic abnormality in acute myeloid leukemia

Deletion of chromosome Xq23 has been reported in a number of solid tumors, including soft tissue sarcoma, malignant melanoma, astrocytoma, and adenocarcinoma. The deleted Xq often occurs in a setting of very complex karyotypic changes. A similar abnormality has also been described in rare cases of acute myeloid leukemia (AML) but in no other hematologic malignancies. In this study, we report the occurrence of del(X)(q23) in two cases of AML.     

Tetrasomy 21 as the sole acquired karyotypic abnormality in acute myeloblastic leukemia.

Peripheral blood and bone marrow analysis of a 79-year-old female led to a diagnosis of acute myeloblastic leukemia with differentiation (AML-M2). Chromosome analysis of the unstimulated bone marrow cells revealed 48, XX,+21,+21, and tetrasomy 21 was the sole cytogenetic abnormality in this constitutionally normal female patient.     

Complex karyotypic evolution in B-cell chronic lymphocytic leukemia.

Cytogenetic analysis at diagnosis in a female patient with chronic B-cell leukemia showed a single abnormal clone with a 4p+ abnormality, 46,XX, -4, +der(4)t(4;?)(p16;?). Six additional clones evolved from this clone during the following 4 1/2 years and showed 3p+, 4p-, and 11q- chromosomes in addition to the 4p+ abnormality. Immunoglobulin heavy chain gene rearrangement studies showed two rearranged bands and a faint germline band. Following splenectomy, a strong germline and faint rearranged bands were seen, suggesting that the majority of cells were normal, whereas cytogenetic studies showed that the karyotypically abnormal cells were still present. The combination of cytogenetic and Ig gene rearrangement studies provides detailed information regarding the number of circulating normal and leukemic cells.     

Complex germline rearrangement of BRCA1 associated with breast and ovarian cancer

Germline mutations in BRCA1 predispose to breast and ovarian cancer. Most germline BRCA1 mutations are small insertions, deletions, or single base pair (bp) substitutions. These mutation classes are rarely found as somatic mutations in BRCA1. On the other hand, somatic deletions of multiple mega-base pairs (Mb) including BRCA1, as reflected by loss of heterozygosity, occur frequently in both inherited and sporadic breast and ovarian cancers. To determine whether deletions or rearrangements of hundreds to thousands of bps might contribute to inherited mutation in BRCA1, we developed a Long PCR strategy for screening the entire genomic BRCA1 locus in high-risk families. We evaluated genomic DNA from one high-risk family of European ancestry with BRCA1-linked cancer in which no genomic mutations had been detected using conventional methods. Long PCR revealed a complex mutation, g.12977 ins10 del1039 (based on GenBank L78833), comprising an inverted duplication and deletion in BRCA1 that removes portions of exon 3 and intron 3, including the 5' splice site for intron 3. As a result of the deletion, exon 3 is skipped, leading to a truncated protein and disease predisposition. Unlike previously reported large germline deletions in BRCA1, neither breakpoint resides within an Alu element. The g.12977 ins10 del1039 mutation was not detected among 11 other breast cancer families, nor among 406 breast cancer patients unselected for family history.     

Perforated duodenal ulcer associated with ovarian hyperstimulation syndrome: Case Report

Ovarian hyperstimulation syndrome (OHSS) remains the most serious medical complication of controlled ovarian stimulation. An unusual case of perforated duodenal ulcer following critical OHSS is presented. A 29 year old nulligravid woman with polycystic ovarian syndrome underwent her first attempt at in-vitro fertilization. She was admitted to the hospital with critical OHSS and subsequently found to have a perforated posterior duodenal ulcer. She underwent exploratory laparotomy, antrectomy and gastrojejunostomy. Pathological analysis of her gastric antrum confirmed chronic gastritis and Helicobacter pylori. She required prolonged assisted ventilation, vasopressor support, multiple i.v. antibiotics, blood product replacement and nutritional support. The patient was hospitalized for a total of 47 days and then transferred to a rehabilitation facility for an additional 30 days before being discharged to home. In this critically ill patient with OHSS, severe stress associated with invasive monitoring and multiple medical therapies in the intensive care unit as well as H. pylori infection appear to be the most probable causative factors of her perforated viscus. Prompt recognition of potential complications and proper medical intervention are essential in the management of patients with OHSS. Avoidance strategies are still needed.