Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to > 1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include "coarse face" in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the falx cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the affected individuals. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management.

Clinical findings in two African-American families with the nevoid basal cell carcinoma syndrome (NBCC).

The nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder with variable expressivity. We present the clinical findings on 11 African-American NBCC cases from 2 families and a review of the literature of NBCC in African-Americans. The 2 new families, as well as those previously reported, suggest minimal expression of the basal cell carcinomas and full expression of the other components of the syndrome. The 3 most common findings in the 11 cases were jaw cysts, palmar and/or plantar pits, and calcification of the falx cerebri. Only 44% (4/11) of these cases had one or more confirmed basal cell carcinomas. This frequency is substantially less than that observed in whites (90% with basal cell carcinomas). The relative lack of these skin tumors in African-Americans partly reflects ultraviolet radiation protection resulting from increased skin pigmentation. Future research should help identify the specific mutation(s) in blacks as well as other modifying genes and environmental exposures that may contribute to the varied manifestations of the syndrome.

Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9.

Gorlin syndrome is an autosomal dominant disorder that predisposes to basal cell carcinomas of the skin, ovarian fibromas, and medulloblastomas. Unlike other hereditary disorders associated with cancer, it features widespread developmental defects. To investigate the possibility that the syndrome is caused by mutation in a tumor suppressor gene, we searched for loss of heterozygosity in 16 sporadic basal cell carcinomas, 2 hereditary basal cell carcinomas, and 1 hereditary ovarian fibroma and performed genetic linkage studies in five Gorlin syndrome kindreds. Eleven sporadic basal cell carcinomas and all 3 hereditary tumors had allelic loss of chromosome 9q31, and all informative kindreds showed tight linkage between the Gorlin syndrome gene and a genetic marker in this region. Loss of heterozygosity at this chromosomal location, particularly in hereditary tumors, implies that the gene is homozygously inactivated and normally functions as a tumor suppressor. In contrast, hemizygous germline mutations lead to multiple congenital anomalies.

Immediate postexcision mammography for occult noncalcified breast lesions.

To evaluate completeness of surgical excision, we studied the use of film screen mammography done immediately after excision of occult noncalcified breast lesions in 11 patients. The postoperative mammograms were well tolerated, and allowed high quality films to be obtained. Complete excision was documented in ten patients, and one patient had small artifacts that resolved on follow-up studies. Roentgenograms of the surgical specimen from ten patients showed a discrete lesion in only three. Histologic analysis revealed malignancy in two patients and benign changes in nine. These findings indicate that mammography done immediately after excision of occult noncalcified lesions is more reliable than roentgenograms of the specimen and may be a useful method for confirming extent of excision. This method may also eliminate the present delay of four to six weeks before adequate postoperative follow-up films can be obtained to evaluate excision.

Arthropathy in acromegalic patients before and after treatment: a long-term follow-up study.

The medical records of 90 patients with acromegaly were reviewed. Arthralgias were noted in 76% of the patients with 17% having the onset of joint pain concomitant with the clinical onset of acromegaly. Of 47 patients followed prospectively for 5 or more years after pituitary irradiation, six (12.8%) were unaffected by arthralgias. A statistically higher mean baseline growth hormone level was found for the 19 (40.4%) radiotherapy patients who had severe and disabling arthropathy. Mean intervals between clinical onset of acromegaly and the development of arthropathic symptoms were shorter (4.1 years) for patients over 40 years of age and longer (9.7 years) for those under 31 years of age. Severely affected patients tended to have increased joint spaces in both weight-bearing and non-weight-bearing joints followed by a progressive decrease in joint spaces. Arthropathy is a common complication of acromegaly and may progress independently of a fall in growth hormone, induced by any form of treatment, once significant cartilage overgrowth develops. Cartilage overgrowth is a predisposing factor in the development of an arthropathy associated with the wide range of growth hormone levels characteristic of acromegaly.

Hepatosplenic candidiasis: wheels within wheels.

Eight immunocompromised cancer patients with tissue-proved candidiasis underwent serial abdominal ultrasound (US) and computed tomography (CT). At US, four patterns of hepatic and splenic candidiasis were recognized, one of which the authors call a "wheels-within-wheels" pattern. In addition, periportal linear areas of increased attenuation, possibly calcified, were identified at follow-up, nonenhanced CT. Some abscesses were better seen on nonenhanced CT scans, while others became visible only with enhancement. Although lesions not seen at US were often seen at CT, the opposite was also true. In two cases, pathologic proof of candidiasis was established even when all imaging studies were normal. For maximum imaging sensitivity, patients should be studied with US and nonenhanced and enhanced CT. Even when both US and CT scans are negative, if there is a strong clinical suggestion of candidiasis, open biopsy is recommended.

Hepatic candidiasis in cancer patients: the evolving picture of the syndrome.

Focal hepatosplenic candidiasis has been recognized with increasing frequency in recent years. We reviewed the cases of eight patients seen between 1982 and 1985, and information on 60 patients whose cases have been reported in the world literature. The characteristics of focal hepatosplenic candidiasis include persistent fever in a neutropenic patient whose leukocyte count is returning to normal, often coupled with abdominal pain; an elevated alkaline phosphatase level; and less commonly, rebound leukocytosis. The characteristic "bull's eye" lesions seen with hepatic ultrasound examination or computed tomography generally are not detectable until neutrophil recovery has occurred. Diagnosis can be established only by biopsy evidence of yeasts or pseudohyphae in the granulomatous lesions. Cultures are frequently negative, however, especially in patients who have been pretreated with antifungal agents. We review the evolving nature of hepatosplenic candidiasis, focusing on diagnosis and treatment.

Sinus histiocytosis with massive lymphadenopathy.

Gallium uptake corresponding to the extent of the disease in a patient with histologically proven sinus histiocytosis with massive lymphadenopathy (SHML) is reported. Computerized tomography confirmed the presence of bilateral retrobulbar masses, involvement of both lateral recti, erosion of the bony orbital floor with encroachment of tumor into the right maxillary antrum, and retropharyngeal involvement.

MRI in autonomic failure.

A significant rank correlation between rigidity and putaminal signal dropout on magnetic resonance imaging (MRI) in patients with multiple system atrophy suggests that putaminal degeneration may cause this clinical finding. Absence of putaminal abnormalities on MRI in patients with pure autonomic failure may prove useful in differentiating these two autonomic disorders.

Seventeen year follow-up and autopsy findings in a case of massive osteolysis.

Clinical, radiologic, and pathologic findings in an unusual case of massive osteolysis are described. Peculiar clinical episodes of a foul body odor with fever and erythematous skin lesions, presence of radiographic findings such as acro-osteolysis and periarticular erosions, and the absence of angiomatous or lymphangiomatous dysplasias at autopsy, indicate that this is a new form of massive osteolysis rather than a variant of Gorham disease.

Multiple system atrophy (Shy-Drager syndrome): MR imaging.

The Shy-Drager syndrome (SDS) is a form of progressive autonomic nervous system failure (PAF) with orthostatic hypotension and associated extrapyramidal involvement that is often mistaken for Parkinson disease. SDS includes olivopontocerebellar atrophy and striatonigral degeneration which is attended by PAF. Eight patients with SDS were studied on a 0.5-T superconducting system utilizing T1-weighted inversion recovery (IR) and T2-weighted spin-echo pulse sequences and also on a 1.5-T system using spin-echo sequences. With IR sequences, atrophy of the putamina was demonstrated in patients with SDS that is consistent with findings of neuronal loss in these nuclei reported on postmortem examinations. An abnormal decrease in signal intensity of the putamina, particularly along their lateral and posterior portions, was also detected, predominantly on T2-weighted sequences, and in three cases on T1-weighted spin-echo sequences. Abnormalities were detected on both imagers but were shown with greater clarity on the 1.5-T device. SDS is the first disease in which convincing basal ganglia changes have been shown in vivo exclusively by MR imaging.

Magnetic resonance imaging in Huntington disease.

Four patients with Huntington disease were imaged using CT and inversion-recovery magnetic resonance (MR) imaging. In all four patients the caudate nucleus and corpus striatum were well demonstrated and noted to be atrophic. MR is believed to be superior to CT for imaging morphologic changes of Huntington disease.

Giant rectus sheath hematomas of the pelvis complicating anticoagulant therapy: CT findings.

We present three cases of giant rectus sheath hematomas in patients on anticoagulant therapy studied by ultrasound and CT. The anatomy of the posterior rectus sheath is described to explain why blood tracks into the pelvis when the hematomas enlarge.

Nutrient foramina in the phalanges of the hands.

The normal distribution and size of nutrient foramina in the terminal and middle phalanges of the fingers, which appear as radiolucencies on hand radiographs, is described. In a study based on the antero-posterior (AP) hand films of 218 patients, we found no evidence that the foramina were more frequently seen in childhood. When age is disregarded in statistical analysis, the foramina are more frequently observed in women than in men. In both sexes foramina are seen most often in the middle phalanges. We have found that the upper limit of normal of foraminal diameters is 1 mm (uncorrected for enlargement) and this permits recognition of enlargement of the foramina which can occur in disorders such as Gaucher's disease, sickle cell anemia and thalassemia.

Enlarged phalangeal nutrient foramina in Gaucher disease and beta-thalassemia major.

The posteroanterior hand films of 10 of 15 patients with Gaucher disease demonstrated enlarged nutrient foramina when compared with a control group matched for patient gender and age. Similar findings were also noted in seven of 22 patients with beta-thalassemia major. Enlargement of nutrient foramina in the hands may indicate the existence of a hematologic disorder.

Radiolucent "zones" in parietal bones seen on computed tomography: a normal anatomic variant.

Computed tomographic images of the head, photographed at wide window settings to better demonstrate bone details, show radiolucencies in the parietal bones especially on sections taken at the vertex of the skull. These represent a normal finding and should not be mistaken for pathology.