Hypomelanosis of Ito

We report two patients with hypomelanosis of Ito, one whose afflictions were limited to the pigmentary skin abnormalities and another with systemic involvement of the neurological and gastrointestinal system. These case reports give support to the importance of establishing hypomelanosis of Ito as occurring with or without systemic involvement.     

Hypomelanosis of Ito

The main peculiarities of the hypomelanosis of Ito (HI) or incontinentia pigmenti achromians are shown. The most frequent and severe complications of this multisystemic neurocutaneous disease are reviewed. The most severe complications concern to the central nervous system (CNS), mental retardation and epilepsy--both present in more than 50% of cases--being the two most severe and frequent disorders. About 10% of patients with HI show infantile spasms during the first year of life and another 10% have autistic behavior. Moreover, other complications can be observed in some patients. These complications consist of ocular, musculoskeletal and oral alterations, hypotonia, macrocephalia, microcephalia, congenital cardiac malformations, urological and genital malformations and other rarer disorders. Chromosomal anomalies, especially translocations or mosaicisms type are found in about 50% of cases. The study, however, can show the chromosomal abnormalities in the karyotype performed in fibroblasts of the hypopigmented skin while it may be normal in the blood and in skin unaffected.     

Hypomelanosis of Ito with unusual associations

Hypomelanosis of Ito (HOI) is a neurocutaneous disorder which clinically is a well-characterised disease, in which chromosomal instability may be a component. Various neurological and other non-cutaneous malformations have been reported in association with the characteristic swirling pattern of hypopigmentation. We report two cases of this rare condition, one with hitherto unreported associations.     

Hypomelanosis of Ito: a syndrome requiring a multisystem approach

The increasing frequency of stent implantation into coronary arteries is based mainly on assumptions. One of these assumptions is that stents may prevent restenosis. Stents can prevent restenosis as has been shown in two randomized studies (Stress I and Benestent I), but only in large (> 3.0 mm) vessels with short denovo lesions. Despite the very tight selection of patients suitable for stent implantation in these two studies, the advantage for stents remained small (about 10% less restenosis) and appeared to decrease with time following intervention. There is increasing concern about the extension of stenting in an "unrestricted strategy". This concern was expressed in the ACC Expert Consensus Document which was published recently (JACC 28, No 3, September 1996: 782-794). Based on lack of data for most of the presently used stent indications the expert group recommended a more selective strategy for the implantation of stents into coronary arteries.     

Bilateral neuropathologic changes in a child with hemimegalencephaly

Evaluation of a 7-month-old girl with developmental delay and intractable seizures revealed hemispheric asymmetry and an enlarged right cerebral hemisphere. Because of a history of seizures refractory to medical therapy, she was admitted for right hemispherectomy, but died of complications of surgery. Postmortem brain examination revealed asymmetric enlargement of the right cerebral hemisphere but no gross abnormalities in the left hemisphere. Microscopic examination demonstrated bilateral neuropathologic changes consistent with severe cortical dysplasia in the right cerebral hemisphere and mild cortical dysplasia in the left. Although white matter abnormalities in the unaffected hemisphere have been reported in hemimegalencephaly, bilateral cortical abnormalities, not reported previously in patients with hemimegalencephaly, may account for the varied clinical outcome with medical therapy or after hemispherectomy.     

Membranous lipodystrophy: a clinicopathological study of six cases

Membranous lipodystrophy apparently is a new disease, first reported and named by Nasu and associates 31 in 1971. We have collected six cases of this disease. The initial manifestation was articular pain at adolescence. Symmetrical changes in the bones of the extremities then appeared and the disease seemed to progress slowly with age. The younger patients exhibited only skeletal pain or fractures, while the older patients had some neuropsychiatric changes. Three of the patients died in middle age. The cystic bone lesions contained a yellow, lipid-like substance which histologically showed a characteristic membranocystic appearance. Electron microscopic study showed unique features, but biochemical analysis of the substance did not reveal a definable abnormality.     

Tumoural lipocalcinosis: a clinicopathological study of 20 cases

Envelope components were separated from Venezuelan, Eastern, and Western equine encephalomyelitis viruses after treatment of the virions with detergent. Vaccines prepared from the envelope component were capable of stimulating mice to produce humoral antibodies. Protective efficacy studies were performed using mono-, di-, and trivalent vaccine combinations. These elicited varying degrees of homologous protection, and Eastern and Venezuelan equine encephalomyelitis envelope products appeared to confer protection to mice challenged with Western equine encephalomyelitis virus.     

Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases

PURPOSE: Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS: We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS: Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS: Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.     

Fulminant Guillain-Barré syndrome with universal inexcitability of peripheral nerves: a clinicopathological study

The pathological basis of nerve inexcitability in Guillain-Barré syndrome has not been established with certainty. We report the clinicopathological findings in a 67-year-old patient with fulminant Guillain-Barré syndrome who died 18 days after onset. Three serial electrophysiological studies revealed nerve inexcitability. Antibodies to Campylobacter jejuni were present but there was no antiganglioside reactivity. Spinal root sections revealed extensive and almost pure macrophage-associated demyelination with occasional presence of T lymphocytes and neutrophil leukocytes. Conversely, in femoral, median, and sural nerves the outstanding lesion was axonal degeneration, with some denuded axons remaining. Unmyelinated fibers, posterior root ganglia, and dorsal columns were preserved. Endoneurial postcapillary venules showed plump endothelial cells with loss of their tight junctions. We conclude that both primary demyelination and axonal degeneration secondary to inflammation account for nerve inexcitability. Our findings lend support to the hypothesis of increased endoneurial pressure as the cause of wallerian degeneration in nerve trunks.     

Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.     

Fibromuscular dysplasia of the internal carotid artery: a clinicopathological study

A combination of Southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization techniques was used to map YACs, cosmids and DNA markers from the Xp11.2 region relative to the X chromosome breakpoint of the renal cell carcinoma-associated t(X;1)(p11;q21). The position of the breakpoint could be determined as follows: Xcen-OATL2-DXS146-DXS255-SYP-t(X;1)-TFE 3-OATL1-Xpter. Fluorescence in situ hybridization experiments using TFE3-containing YACs and cosmids revealed split signals indicating that the corresponding DNA inserts span the breakpoint region. Subsequent Southern blot analysis showed that a 2.3-kb EcoRI fragment which is present in all TFE3 cosmids identified, hybridizes to aberrant restriction fragments in three independent t(X;1)-positive renal cell carcinoma DNAs. The breakpoints in these tumors are not the same, but map within a region of approximately 6.5 kb. Through preparative gel electrophoresis an (X;1) chimaeric 4.4-kb EcoRI fragment could be isolated which encompasses the breakpoint region present on der(X). Preliminary characterization of this fragment revealed the presence of a 150-bp region with a strong homology to the 5' end of the mouse TFE3 cDNA in the X-chromosome part, and a 48-bp segment in the chromosome 1-derived part identical to the 5' end of a known EST (accession number R93849). These observations suggest that a fusion gene is formed between the two corresponding genes in t(X;1)(p11;q21)-positive papillary renal cell carcinomas.     

Microphthalmos with orbital cyst: a clinicopathological report

The clinical and histopathological findings in a case of microphthalmos with orbital cyst is described. The clinical interesting feature of this case was the bilateral coloboma which represented interference in the development of the eye at different stages of embryonic life.     

Factors associated with endodontic flare-ups: a prospective study

The purpose of this prospective study was to assess the incidence of flare-ups (a severe problem requiring an unscheduled visit and treatment) among patients who received endodontic treatment by the two authors in their respective practices during a period of one year, and also to examine the correlation with pre-operative and operative variables. The results showed an incidence of 1.58% for flare-ups from 1012 endodontically treated teeth. Statistical analysis using the chi-square test (P<0.05) indicated that flare-ups were found to be positively correlated with multiple appointments, retreatment cases, periradicular pain prior to treatment, presence of radiolucent lesions, and patients taking analgesic or anti-inflammatory drugs. In contrast, there was no correlation between flare-up, and age, sex, different arch/tooth groups and the status of the pulp.     

Unsuspected gallbladder cancer diagnosed by laparoscopic cholecystectomy: a clinicopathological study

Laparoscopic cholecystectomy (LC) for gallstones has become a popular treatment modality, but LC for gallbladder cancer is not yet established and its prognosis is still unknown. We clinicopathologically studied unsuspected gallbladder cancer presenting at pathologic evaluation after LC. The entire cross section of gallbladders after 456 LCs was histologically examined. The presence of malignant lesions was confirmed in 13 (2.85%) of 456 cases. The preoperative diagnoses were gallstones in 5 patients, gallbladder polyps in 5, gallstones with gallbladder polyps in 2, and gallstones with adenomyomatosis in 1. The carcinoma had invaded the mucosa in 7, the proper muscle in 2, and the subserosa in 3; the serosa was exposed in 1. The tumor size ranged from 2 mm to the entire gallbladder. An additional resection was performed in 2 patients. During the mean follow-up period of 25.9 months, 1 patient died of recurrence at 8 months while 1 demonstrated recurrence at the port site 1 year after surgery. No other patients have had any recurrence to date. Since early gallbladder cancer removed laparoscopically can be expected to have a satisfactory outcome, diagnostic and therapeutic LC is recommended in cases where total biopsy is indicated. However, in every case, extreme caution needs to be exercised to prevent the dissemination and implantation of cancer cells at the port site.     

The significance of microabscesses in liver transplant biopsies: a clinicopathological study

BACKGROUND: Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational drug of abuse that is known to damage brain serotonergic neurons in animals and possibly humans. Few functional consequences of MDMA-induced serotonin (5-HT) neurotoxicity have been identified, either in animals or humans. This study sought to determine whether individuals with a history of extensive MDMA use showed evidence of memory impairment, because brain serotonin has been implicated in mnemonic function. METHOD: The authors compared 24 abstinent MDMA users and 24 control subjects on several standardized tests of memory, after matching subjects for age, gender, educational level, and vocabulary score (a surrogate of verbal intelligence). The authors also explored correlations between changes in memory function and decrements in CSF 5-hydroxyindoleacetic acid (5-HIAA), which serves as a marker of central 5-HT neural function. RESULTS: Greater use of MDMA (total milligrams per month) was associated with greater impairment in immediate verbal memory (p < 0.02) and delayed visual memory (p < 0.06). Furthermore, lower vocabulary scores were associated with stronger dose-related effects, with men having greater dose-related deficits than women. Lastly, lower concentrations of CSF 5-HIAA were associated with poorer memory performance. CONCLUSION: Abstinent MDMA users have impairment in verbal and visual memory. The extent of memory impairment correlates with the degree of MDMA exposure and the reduction in brain 5-HT, as indexed by CSF 5-HIAA.     

Radiation myelopathy: a clinicopathological study with special reference to correlation between MRI findings and neuropathology

We describe magnetic resonance imaging (MRI) and neuropathological findings in a patient with chronic progressive radiation myelopathy (CPRM). An 81-year-old man with esophageal cancer underwent radiotherapy. Four years later he developed a progressive neurological deficit below the irradiated level of the spinal cord. Neurological examination revealed spastic paraplegia. MRI findings showed an area of high signal intensity on T2-weighted images of the thoracic spinal cord. On the basis of clinical and MRI findings, we diagnosed his condition as CPRM. MRI performed thirteen months after onset of neurological signs revealed mild atrophy of the spinal cord detected on T1-weighted images and an area of high signal intensity within the spinal cord detected on T2-weighted images. Neuropathological examination revealed findings consistent with radiation myelopathy. We speculate that the area of high signal intensity within the spinal cord detected on T2-weighted images might be a result of proliferation of small vessels, which was discovered upon autopsy.     

Observations on the A2 England influenza epidemic: a clinicopathological study

A clinicopathological study of the 1972-1973 A2 England influenza epidemic is presented. In fatal cases early necrosis of myofibrils was present in those patients who died within 24 hours of the onset of the influenza symptoms. At 5 days gross changes were present. These were largely resolved by the eighteenth day of illness. In 42 patients treated at home, transient ECG changes were found in 18 cases. These included ST-segment deviation, T-wave inversion, flattening of the T wave, sinus bradycardia, sinus tachycardia, nodal rhythm, and atrial fibrillation. Permanent changes were observed in one patient and in an additional patient admitted to hospital with permanent A-V block.     

Gangliogliomas: a clinicopathological study of 25 cases and review of the literature

The histopathological, clinical, and radiological findings in 25 patients (median age 20.5 years; range 1.7-64.2 years) with gangliogliomas were assessed to correlate degree of astrocytic anaplasia and proliferative potential with recurrence or survival. Most patients (64%) presented with seizures (median Karnofsky Performance Score 90%; range 70-100%). Computerized tomography and magnetic resonance imaging showed nonspecific abnormalities. Neoplastic ganglion cells were defined as heterotopic, irregularly grouped, or having more than one nucleus of bizarre shape or size. The astrocytic component was moderately anaplastic in 15 cases and highly anaplastic (HAA) in 10. Eight patients had gross total resection, 11 had subtotal resection, and six underwent biopsy. Ten patients (five gross total resection, three subtotal resection, two biopsy) had no further treatment, 15 underwent external irradiation, and five had adjuvant chemotherapy. Twenty-four patients are alive 15-394 weeks (median 203.5 weeks) postoperatively; one with ganglioglioma-HAA died at 65 weeks. No tumor recurred after gross total resection. Duration of preoperative symptoms < 1 year, greater anaplasia, and age > 30 years at diagnosis may have increased the risk of recurrence after subtotal resection or biopsy by four, three, and two times, respectively (not significant). Bromodeoxyuridine labeling index (BUdR LI) was < 1% in eight non-recurring tumors and 1.3% in another recurring twice (second recurrence LI = 1.6%). Most patients with ganglioglioma have a good prognosis. After gross total resection, only observation is required. After subtotal resection or biopsy, recurrence is possible. BUdR labeling may guide further therapy.     

Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.