Rare cause of natural death in forensic setting: hemophagocytic syndrome.

We report about the case of a sudden unexpected death of a 25-year-old male suffering from infectious disease. An autopsy was ordered with no final premortem diagnosis. Microscopic and microbiological examination revealed a pneumococcal bronchopneumonia and hemophagocytic lesions in the bone marrow. After integrating clinical and autopsy reports as well as additional postmortem investigations, the cause of death was found to be infectious-triggered hemophagocytic syndrome (HPS) with a final cytokine storm. This seems to be the first reported fatal case of a reactive form of HPS associated to Streptococcus pneumoniae to the best of our knowledge. HPS is a dangerous hyperinflammation with highly characteristic, but nonspecific, laboratory findings and symptoms. Autopsies in such cases must be carefully performed and include systematic tissue sampling done by an experienced pathologist.

Aceruloplasminaemia: a family with a novel mutation and long-term therapy with deferasirox.

Ceruloplasmin is a member of the multicopper oxidase family that plays a major role in the transport of iron in the body. Aceruloplasminaemia (ACP) is a rare disease and is clinically identified by iron overload in liver, pancreas, brain, and other organs, and by microcytic anaemia. So far, the iron chelator deferasirox was given for therapy only up to 6 months due to side effects. Here, we describe a novel mutation leading to ACP and report for the first time a long-term therapy, that is, 2 years with deferasirox. ACP was diagnosed in 3 siblings using clinical and biochemical characteristics, HFE and ceruloplasmin mutational analysis, liver biopsy, brain-, liver-, and heart-MRI. For iron depletion, a starting dose of deferasirox 7.5 mg/kg/day was increased to 15 mg/kg/day and maintained at 4-7.5 mg/kg/day with a patient follow-up for 2 years. A novel homozygous mutation of the ceruloplasmin gene on chromosome 3 (3q23-q25, exon 12, G708S) was found. Iron was selectively and successfully removed by long-term therapy with deferasirox, as confirmed by follow-up liver biopsies, normalisation of serum ferritin concentrations, and improved glucose metabolism. Unexpectedly, iron depletion ameliorated anaemia. Low-dose deferasirox is an effective and safe long-term treatment option for patients with ACP.

[Proposals for standardization of autopsy reports]. / Vorschläge zur standardisierten Abfassung von Obduktionsberichten.

The decline in the number of autopsies not only in Germany has been attributed to several reasons. Complaints of clinicians about a non-uniform layout of autopsy reports may be one important reason. The lack of initiatives concerning standardization of autopsy reports contributes to a poor comparability of autopsy reports from different institutions and even within one institution. In order to promote harmonization of a protocol for autopsy results proposals for a standardization of autopsy protocols are given. These proposals are based on using modules for different parts of the autopsy protocols, thus giving different institutions the possibility to modify these modules.

The carotid bodies in cyanotic heart disease.

The morphological findings of the carotid bodies of two cases with cyanotic heart disease are presented. The first case, a 14-year-old girl with atrial and ventricular septal defect accompanied with atresia of the tricuspidal valve showed a life-long history of pulmonary hypertension and hypoxaemia. The carotid bodies were not enlarged, but the diameters of the glomic lobules were increased and its margins were sometimes blurred. There was a marked increase of glomic tissue within the carotid bodies. The ratio of chief to sustentacular cells remained unchanged. The second case, a 59-year-old man with a double inlet left ventricle, had a history of pulmonary hypertension and hypoxaemia of more than 23 years. The carotid bodies as well as the diameters of the glomic lobules were much more enlarged than in case one. There was an increase of glomic tissue within the carotid bodies, too. The histological examination showed a marked increase of sustentacular and Schwann cells. These results show that the findings of carotid bodies in cyanotic heart diseases may be different depending on the duration of hypoxaemia.

Serotonin immunoreactivity in the carotid body of adult humans.

The distribution of serotonin immunoreactivity (-IR) was studied in adult human carotid bodies, obtained at post-mortem, using both the peroxidase-antiperoxidase method on paraffin sections and a double-labelling immunofluorescence on frozen sections. Antibodies against synaptophysin and protein gene product (PGP) 9.5 were used for identification of serotonin-IR cells. Serotonin-IR was demonstrable in the carotid bodies of adult humans and it was coexpressed mostly with synaptophysin or PGP 9.5 in type I cells. Some serotonin immunopositive type I cells were located in close proximity to capillaries. Serotonin-IR was also observed in a few endothelial cells.

[Primary malignant melanoma of the gallbladder. Case report and literature review]. / Primäres malignes Melanom der Gallenblase. Fallbericht und Literaturübersicht.

An autopsy case of a 57-year-old man with primary melanoma of the gallbladder is described. The tumour appeared as a polypoid mass, measuring 4 cm in diameter. Microscopic examination revealed mostly spindle cells with vesicular nuclei and large nucleoli. Many cells stained positively for S 100 protein and HMB 45 using immunohistochemistry and they contained dark brown pigment that stained as melanin pigment with Fontana-Masson. The tumour had metastasised and affected the stomach, the duodenum, the jejunum, the lung, the brain and a bronchopulmonary lymph node. Examination of the skin and both eyes showed no abnormality. Primary malignant melanomas of the gallbladder are very rare. Only 23 cases have been described. These cases are summarized and reviewed.

[The number of autopsies at the Chemnitz Institute of Pathology before and after unification (1987-1992)]. / Die Anzahl der Obduktionen im Institut für Pathologie Chemnitz vor und nach der Wiedervereiningung (1987-1992).

The numbers of autopsies performed at the Institute of Pathology in Chemnitz before and after German unification (1990) were compared (1987-1992). In 1991 and 1992 a decrease of up to 40% was observed. In the former GDR an autopsy was possible without agreement of the relatives, whereas since unification the relatives have the power to forbid an autopsy. This was the principal reason for the dramatic decline in the past 2 years. Another relevant factor is the difficult economic situation of most hospitals in the region, preventing the arrangement of more autopsies. Analysis also shows the important role of physicians in clinics regarding the autopsy rates.

[Aggressive angiomyxoma of the vulva and perineum]. / Aggressives Angiomyxom der Vulva und des Perineums.

Reported in this paper are two cases of aggressive perineovulvar angiomyxoma. Soft, painless tumours with gelatinous cut surface were detected in either patient, two women aged 32 and 46 years. Histological findings included fibromyxoid stroma with spindle-shaped and stellate cells as well as vascularization in striking abundance. Most of the vessels were thin-walled. There was no plexiform arborization. Strongly atypical nuclei or mitoses or necrotic foci were not recordable. The tumour exhibited infiltrative growth. Tumour cells could be immunohistochemically associated with antibodies against vimentin, whereas negative responses were recorded from antibodies against S-100 protein, factor-VIII-associated protein and pancytokeratin. Aggressive angiomyxoma is a biologically benign neoplasia prone to recurrence and typically localized in soft tissue of the pelvic region. Metastases so far have never been found. Wide local excision has proved to be the optional therapeutic approach.

Chemoreceptor A-fibres in the human carotid body contain tyrosine hydroxylase and neurofilament immunoreactivity.

Previous retrograde tracing studies on rat and guinea-pig showed a projection of sensory tyrosine hydroxylase-immunoreactive neurons to the region of the carotid bifurcation via the carotid sinus nerve. In the present study, focussing on the sensory innervation of the human carotid body, antisera to tyrosine hydroxylase and other catecholamine synthesizing enzymes were applied for an immunohistochemical investigation of carotid bodies obtained at autopsy. In addition, an array of antisera directed to non-enzyme antigens known to be present in viscero-afferent neurons were incorporated in the study. The glomic lobules consisting of glomus cells and sustentacular cells contained a variable number of enzyme-immunoreactive glomus cells. Arteries were supplied by nerve fibres displaying the full phenotype of sympathetic noradrenergic axons, i.e. immunoreactivity to tyrosine hydroxylase, aromatic-L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. The glomic lobules, however, were densely innervated by tyrosine hydroxylase-immunoreactive axons lacking immunoreactivity to aromatic-L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. These fibres reacted with neurofilament 160kD-antibody but were devoid of immunoreactivity to all neuropeptides tested (calcitonin gene-related peptide, somatostatin, substance P). Ultrastructurally, tyrosine hydroxylase/neurofilament 160kD-immunoreactive axons gave rise to large axonal swellings filled with mitochondria and vesicles, and established extensive contacts to glomus cells. Nerve bundles surrounded by a perineural sheath contained both myelinated (2.0-2.8 microns in diameter) and unmyelinated (0.14-3.0 microns) tyrosine hydroxylase-immunoreactive axons. Most of the unmyelinated immunoreactive axons were running singularly within a Schwann cell-sheath. Judged from the pattern of immunoreactivities as well as their preterminal and terminal ultrastructure, tyrosine hydroxylase-immunoreactive axons innervating glomus cells are of sensory origin. Although final proof by retrograde tracing cannot be presented in man, this conclusion is supported by experimental evidence in laboratory animals. The myelinated immunoreactive axons correspond to chemoreceptor A-fibres whereas the classification of the large unmyelinated immunoreactive axons has yet to be established. The lack of immunoreactivity to the dopamine-synthesizing enzyme, aromatic-L-amino-acid-decarboxylase, in this fibre type does not support the view of dopamine being the primary transmitter of chemoreceptor afferents.

Substance P- and calcitonin gene-related peptide-like immunoreactivities in the human carotid body studied at light and electron microscopical level.

The distribution of substance P- (SP-) and calcitonin gene-related peptide-like immunoreactivities (CGRP-LI) was studied in the human carotid body at the light and electron microscopic level. Of the different compartments of the carotid body, the glomic lobules received the densest innervation by SP/CGRP double-labelled axons, followed by interlobular arteries and interlobular connective tissue. Ultrastructurally, preterminal SP/CGRP-LI axons are unmyelinated and measure 0.09-1.02 micron in diameter with a median diameter of 0.28 micron (calculated conduction velocity: 0.5 m/s). Within the glomic lobules, vesicle-containing varicosities are numerous around glomus cells, but only few of them directly contact (non-synaptically) glomus cells. The findings are consistent with the existence of two populations of SP/CGRP-LI C-fibers, one of them probably representing chemoreceptor C-fibers, the other belonging to the ubiquitous vascular sensory innervation. In addition to its localization in nerve fibers, CGRP-LI also occurs in dense core vesicles of a subpopulation of glomus cells. In this regard, the human carotid body is unique among mammalian species studied so far, which severely hampers the interpretation of pharmacological data obtained in laboratory animals in terms of human physiology.

Peripheral arterial chemoreceptors and hypertension.

Functional studies in humans and animals with essential hypertension have shown a hyperventilation under resting conditions and striking respiratory and circulatory reactions to hypoxic and hyperoxic tests. There is some evidence that these reactions are due to enhanced activity of the peripheral arterial chemoreceptors. In contrast, in secondary (renal) hypertension such findings could not be observed. Many morphological, morphometrical and biochemical studies have been performed on the carotid bodies of a variety of hypertensive patients and animal models. Whilst their structure and catecholamine content are changed in hypertension, there are many differences in different types of hypertension and, furthermore, a convincing link between the morphological and biochemical findings from the carotid body studies and their functional overactivity has not been shown. Some of these alterations are caused by the elevated blood pressure (e.g. vascular pathology); others are the expression of general disturbances in the hypertensive disease state (e.g. differences in catecholamine content) whilst others are probably of genetic origin but independent of elevated blood pressure (carotid body volume in different rat models of hypertension). This paper reviews the findings on carotid body structure and function in a variety of animal models of hypertension and in primary and secondary human hypertension.

A case of double inlet left ventricle in a 59-year-old man.

An autopsy case of a 59-year-old man with double inlet left ventricle with a rudimentary right ventricle and discordant ventriculo-arterial connexion is reported. No surgery was performed during his life time and all clinical and echocardiographical findings had led to the diagnosis of a ventricular septal defect. The correct diagnosis could only be made after autopsy.