Short hard palate in prenatal trisomy 21.

OBJECTIVE: The aim of the present study was for the first time to examine on postmortal material the total midpalatal length of the hard palate and the length of its two components (the maxillary and palatine parts) in trisomy 21 fetuses, and to compare the results to normal standards. DESIGN: Material from 31 human fetuses with genetically verified trisomy 21 was studied. The fetuses were derived from legally induced or spontaneous abortions. Palates were, after sectioning, radiographed in lateral projection (Grenz Ray radiographic apparatus). Cephalometric measurements were performed with a digital caliper. Statistically, the length measurements for the two groups were compared, adjusting for crown rump length (CRL) through linear regression. At two specific ages (150 and 170 mm CRL), the length of the palatal components in trisomy 21 was compared to normal standards. RESULTS: For CRL 150 mm and CRL 170 mm it appears that all three palatal lengths, total length, maxillary length, and palatinal length are significantly shorter in fetuses with trisomy 21. CONCLUSION: The main conclusion of our study is that the total palatal length in prenatal trisomy 21 is shorter than normal and that this is due both to a shortness of the maxillary and the palatine components of the hard palate.

A histological and radiological investigation of the nasal bone in fetuses with Down syndrome.

OBJECTIVES: Previous studies of nasal bone development in Down syndrome have used radiographs or ultrasound for the detection of nasal bone length or nasal bone absence. The aim of this study was to investigate the presence and size of the nasal bones in postmortem Down syndrome fetuses by means of radiographs and histological examination. METHODS: Thirty-three aborted human fetuses (gestational age 14-25 weeks) with Down syndrome were included. A mid-sagittal tissue block was excised from the skull base to the foramen magnum and along the lateral aspect of the spine. Radiographs of the tissue block were taken in lateral, frontal and axial projections. The length of the nasal bone was measured. The tissue blocks were cut in serial sections and stained. The crown-rump length (CRL), foot length (FL) and number of ossified bones in the hand and foot (CNO) were recorded. RESULTS: A total of 8/33 fetuses had bilateral nasal bone absence and two had unilateral absence. In fetuses with radiographically diagnosed nasal bone absence, no nasal bone could be found histologically. The majority of the Down syndrome fetuses had CRL, FL and CNO values within the range of those for normal age-matched fetuses. Nasal bone length was normal or reduced. CONCLUSIONS: Absence of the nasal bone was registered by postmortem examination in one-third of fetuses with Down syndrome. In some fetuses this could be a result of delayed maturation associated with Down syndrome. The phenotypic differences in nasal bone appearance may reflect genotypic differences in the Down syndrome group.

Histological investigation of the palatine bone in prenatal trisomy 21.

OBJECTIVE: The purpose of the present study was to investigate the horizontal part of the palatine bone in palates from human fetuses with trisomy 21 to improve the phenotypic classification of the genotypic anomaly. METHODS: Material from 23 human trisomy 21 fetuses was included in the study. The crown rump lengths of the fetuses ranged from 80 mm to 190 mm, corresponding to about 12 to 21 weeks of gestational age. The material was examined histologically. RESULTS AND CONCLUSIONS: Histological examination demonstrated four different palatal phenotypes on the basis of the development of the horizontal part of the palatine bone: type I, palatine bone complete; type II, the mesial region of the horizontal part of the palatine bone is lacking; type III, complete absence of the horizontal part of the palatine bone; and type IV, auxiliary bones in the region of the transpalatine suture. This finding shows that different types of malformations may occur in the horizontal part of the palatine bone in human trisomy 21 fetuses.

Craniofacial tissues including tooth buds in fetal hypohidrotic ectodermal dysplasia.

OBJECTIVE: Hypohidrotic ectodermal dysplasia (HED) comprises defects in hair, teeth, and sweat glands. Disturbances in other ectodermal tissues have been associated with the condition. Our objective was to examine ectodermal craniofacial structures histologically in a fetus with HED and to compare the findings to similar structures in normal control fetuses. MATERIALS AND METHODS: A male fetus diagnosed with HED was therapeutically aborted in the 15th week of gestation. One male and two female healthy fetuses were used as normal controls. All fetuses were examined with parental consent, and had comparable sizes. Their bone maturation stage in the hand was identical. Tissue blocks from the craniofacial region were excised from all fetuses and prepared for histological analysis (formalin fixed, stained with toluidine blue or Alcian blue). The tissues examined were: tooth buds, skin and skin appendages, oral mucosa including minor salivary glands, major salivary glands, lacrimal glands, and adenohypophysis. RESULTS: Fewer tooth buds, minor salivary glands, and hair follicles were observed in the HED fetus as compared to controls. The structures of the epidermal components in the developing HED organs were loose and disorganised. The adhesion between the ectodermal and mesenchymal organ components in the HED fetus seemed to be disturbed.

Prenatal malformed lumbar vertebral corpora in trisomies 21, 18, and 13, evaluated radiographically and histologically.

The aim of the present study was to compare, both radiographically and histologically, malformed vertebral lumbar corpora in trisomies 21, 18 and 13 with earlier reported normal corporal development in the axial lumbar region. Axial skeletons of human fetuses (GA 15-22 wk) derived from therapeutically induced abortion were investigated in connection with requested autopsy. The number of lumbar vertebral corpora examined for each genotype was as follows: 20 from trisomy 21, 10 from trisomy 18, and 10 from trisomy 13. After radiography in frontal, lateral and axial projections, the individual vertebral corpora were decalcified and horizontally embedded in paraffin. The blocks were serially sectioned and stained with toluidine blue and alcian blue/van Gieson. The radiographic characteristics of the vertebral corpora varied from an almost normal appearance of the corporal bone to complete clefting of the bony corpora. Histological examination showed accumulations of cartilage centrally, in some cases associated with amorphous material. Pronounced metachromatic differences were observed in the cartilaginous ground substance. The study showed identical phenotypic characteristics in the corpora from trisomy 21, trisomy 18, and trisomy 13. It is characteristic of all three genotypes that there are central anomalies, corresponding to the location of the notochord in normal corpora, and marked regional differences in metachromasia in the ground substance of the cartilage.

Pituitary gland and axial skeletal malformations in human fetuses with spina bifida.

The purpose of the present study was to describe the pituitary gland and axial skeleton, including the sella turcica, in human fetuses with spina bifida. Ten fetuses with gestational ages (GA) 15 1/2-28 weeks were investigated radiographically (Faxitron X-ray apparatus) and immunohistochemically. Four of the fetuses have been described previously. The study showed that nine fetuses had minor or no skeletal abnormalities in the vertebral bodies of the spine, and one fetus had severely malformed vertebral bodies. In all cases the sella turcica and the pituitary gland were malformed. Adenopituitary tissue was in all cases located in both the sella turcica and the pharyngeal submucosa. The most severe sella turcica/pituitary gland malformation was seen in the fetus with the malformed spine. The connection between the prenatally registered sella turcica/pituitary gland malformation and the endocrinological status of children with spina bifida should be emphasized in future studies.

Pituitary gland and sella turcica in human trisomy 18 fetuses.

The purpose of this study was to elucidate the phenotypic conditions in the sella turcica/pituitary gland complex in human trisomy 18 fetuses. Fourteen human fetuses with gestational ages from 12 to 39 weeks were included in the study. Normal fetuses at corresponding ages were used as controls. Whole body and special radiographic examination was undertaken before the midsagittal cranial base block, including the pituitary gland, was excised and analyzed histologically and immunohistochemically (keratin wide spectrum [KWS], thyroid-stimulating hormone [TSH], and neurophysin [Nph]). In all trisomy 18 fetuses, TSH-positive adenopituitary tissue was present in the sella and in greater or lesser amounts pharyngeally. The neurohypophysis was Nph-positive and located normally in the sella turcica. The adenohypophyseal tissue reacted either KWS-faint or KWS-negative, whereas KWS-positive reaction occurs in normal fetuses. This circumstance might suggest an altered cytoskeletal structure of the surface ectoderm in the pituitary placode in trisomy 18. The sella turcica was malformed in all the fetuses. Very broad craniopharyngeal canals were observed in some of the fetuses. Because endocrine disorders occur in many congenital malformations, it is essential in future studies to chart the sella turcica/pituitary gland region systematically in different genotypes.

Pituitary gland and sella turcica in human trisomy 21 fetuses related to axial skeletal development.

The purpose of the present investigation was to study the sella turcica/pituitary gland region in trisomy 21 fetuses and to relate the findings in the region to the ossification pattern in the axial skeleton formed by the cranial base and spine. Material from 22 human fetuses with trisomy 21, CRL 80 mm to CRL 190 mm, corresponding to gestational ages from 14 to 21 weeks, was examined and compared with material from gestation-matched normal controls. After radiography, tissue blocks from the cranial base, including the pituitary gland, were examined and compared with those of normal fetuses. Four different types of sella turcica/ pituitary gland morphology were observed. Thirteen fetuses (Type I) were morphologically normal. Minor abnormalities occurred in the sella turcica and pituitary gland (adenopituitary gland tissue pharyngeally) in six fetuses (Types II and III). There was agreement between the histologically recorded deviations in the sella turcica and the radiographic observations of the basisphenoid bone. In three cases (Type IV) out of 22, more pronounced structural abnormalities occurred in the sella turcica, and radiographically the basisphenoid bone appeared cleft. All sella turcica changes observed in trisomy 21 were situated anteriorly in the base of the sella. In all cases the basilar part of the occipital bone was normal. Minor changes in the sella turcica region were mainly accompanied by cervical vertebral abnormalities, while the most severe abnormalities occurred in association with malformations in the lumbar vertebrae. There was no association between sella turcica malformations and the absence or presence of the nasal bone.

A new craniofacial disorder involving hypertelorism and malformations of external nose, palate and pituitary gland.

The aim of the present study was to describe and pathologically evaluate an apparently unreported craniofacial malformation, based on comparison of the cranial midsagittal components with similar components under normal developmental conditions. A severely malformed fetus with a gestational age of about 17 weeks underwent whole body and special craniofacial radiography. Following autopsy dissection, the midsagittal segment of the cranial base, including the eyes, was radiographed in different projections. Midsagittal tissue blocks were serially sectioned for microscopy. Routine stains and immunohistochemical stains were applied. The face was characterized by hypertelorism, absence of external nose but with open shell-like cavities medio-cranially to the eyes, and by a palate fused in the midline and with extensive bony ridges laterally. There was absence of normal nasal cavities, presence of nasal septum and vomer, normal eyes, and nasal ducts covered with nasal mucosa ending blindly in the cartilage. No olfactory bulbs were found. The palatal ridges consisted of bony tissue. The pituitary gland was severely malformed and consisted solely of adenopituitary gland tissue, located in its full extent in the pharyngeal mucosa. There was no sella turcica. From a pathogenetic point of view, it is suggested that the neural crest cells in the frontonasal region of the crest were reduced in amount or late in migration to the midfacial region compared to the neural crest cells to the maxillary region. Therefore, we believe that the malformations observed in the nasal placodes and in the pituitary placode, combined with abnormal migration or abnormal timing of neural crest cells during the craniofacial development, are important factors behind this disorder.

Dorsal root gangliopathia presenting with rapidly progressing sensory polyneuropathy.

A 52-year-old woman developed progressive sensory polyneuropathy leading to death in 1.5 years. Electromyography and peripheral nerve biopsy had revealed severe axonal degeneration. Neuropathological examination showed involvement of all dorsal root ganglia with loss of the bipolar nerve cells, degeneration of the remaining nerve cells, Nageotte's residual nodules, and scattered lymphocytes. The posterior columns of the spinal cord and the sensory spinal roots revealed secondary loss and degeneration of the nerve fibers. The etiology is unknown but an autoimmune-mediated reaction effecting the nervous system is strongly suggested.

Astrocytes in the prenatal central nervous system. From 5th to 28th week of gestation. An immunohistochemical study on paraffin-embedded material.

The CNS from 30 normal fetuses aged 5-28 weeks were studied in GFAP stained paraffin-embedded material. The technique of preparation, autopsy and fixation is described in details. GFAP reacting glial cells developed first in the spinal cord at 7 weeks, and appeared in all regions of CNS during fetal life in a systematic way but with a temporal variation. The supporting and guiding properties of the fibrillary astrocytes are stressed.

The Pi Z allele and hepatic alpha 1-antitrypsin globules in patients with secondary liver cancer.

To evaluate the frequency of false positive globular inclusions, 89 autopsy cases with various malignancies and liver metastases have been examined by immunoperoxidase staining of liver sections and isoelectric focusing of sera. Four subjects with AAT globules in their hepatocytes were found, all of whom had the Pi Z phenotype. Globular inclusions were not found in any subject lacking the Pi Z allele on isoelectric focusing, but in 3 subjects with the Pi Z phenotype no hepatocytic globules were found.

Central pontine myelinolysis. A case report with typical neuropathological findings.

A case of central pontine myelinolysis (CPM) in an alcoholic patient with severe electrolyte changes is presented. Data in the literature suggest that it is safe to correct severe symptomatic hyponatremia to a value of 125-130 mEq/1 in 24 h. At the present time acute severe hyponatremia carries a bad prognosis if not treated with hypertonic NaCl solution. Electrolyte abnormalities are not the sole cause of CPM.

Demonstration of alpha 1-antitrypsin in hepatomas.

Sixty-nine primary malignant hepatomas were examined for the presence of alpha 1-antitrypsin (alph 1-AT) in tumor cells using immunohistochemical methods. Twenty-eight tumors showed positivity for alpha 1-AT. The reaction was globular and PAS-positive in 12 hepatocellular tumors and thus simulated the pattern of alpha 1-AT accumulation in hepatocytes in subjects carrying the Z-gene for alpha 1-AT. In fact, eight of these 12 tumors presented this pattern in the nontumours liver tissue. In ten hepatocellular tumors the reaction was finely granular throughout the hepatocytic cytoplasm, but was present in only a small number of cells. Still fewer cells were positive in six cholangiocarcinomas. The globular alpha 1-AT in tumor cells may be genetically determined when associated with the Z-gene. A reappearance of fetal gene products may be assumed in three hepatocarcinomas with globules positive for alpha-fetoprotein as well as alpha 1-AT.

Does the Z gene variant of alpha-1-antitrypsin predispose to hepatic carcinoma?

In 10 of 56 patients with primary liver carcinoma the nontumorous hepatocytes contained diastase resistant, periodic acid-Schiff positive and alpha-1-antitrypsin positive (immunoperoxidase technique) globules. This is a frequency of 18 per cent among patients with liver carcinoma against 6 per cent in an unselected autopsy series. The tumors were of the hepatocellular or mixed type in nine of the 10 patients, and the frequency among such patients was 23 per cent. We consider that these globules indicate a carrier of the protease inhibitor allele of the Z gene variant (single or double).

Periodic acid Schiff-positive non-glycogenic globules in hepatocytes. Differential diagnostic aspects in screening for alpha-1-antitrypsin globules in an autopsy material.

Thirty-eight subjects with diastase-resistant PAS-positive cytoplasmic globules in hepatocytes were found among 238 autopsies. In 15 of the 38 subjects the globules were antigenically alpha-1-antitrypsin, in 23 subjects they were not. The latter globules were found in centrilobular regions, the alpha-1-antitrypsin globules mainly in periportal regions. The non-alpha-1-antitrypsin globules showed less differences in size (6-10 mu) and a smaller number per hepatocyte (1-7) than the alpha-1-antitrypsin globules (1-40 mu and 1-30 per cell). The non-alpha-1-antitrypsin globules were only demonstrated in livers with centrilobular sinusoidal dilatation having, in all cases but one, also centrilobular, confluent necrosis. This type of globules can be assumed to be of differential diagnostic importance mainly in an autopsy material. The nature of these globules is discussed.

Reliability of histo-pathological diagnosis of squamous epithelial changes of the uterine cervix.

The reliability of histological diagnosis of squamous epithelial changes was tested by letting 13 pathologists read 1,001 consecutive cervical biopsies twice. Intra-observer and inter-observer agreement, variance, and deviation of diagnosis were determined. The diagnostic ability showed great individual variation and no significant correlation to experience in pathology. The diagnosis of invasive cancer had a high diagnostic specificity, and the diagnostic sensitivity of the diagnosis of no significant epithelial changes was high too. The reliability of the diagnosis of dysplasia and carcinoma in situ proved unsatisfactory.