Amitosis: a historical misinterpretation?

"The problem of amitosis" (Bucher, 1971) has historical, theoretical, formal, and methodological aspects. Most cases of amitosis described during the past 125 years have proved to be misinterpretations of incomplete mitoses. Binucleate cells and occasionally dumbbell-shaped restitution nuclei are formed as the result of mitotic inhibitions, which increases with tissue differentiation. Until recently, binucleate cells in the myocardium have been interpreted as products of amitotic nuclear divisions, since mitoses are not found in human myocardium. However, mitoses are found in postnatal pig hearts fixed immediately after death. The mitotic index declines from 2.2% at day ten to 0.3% at day thirty during postnatal life. Delayed fixation yields degenerated prophase and telophase nuclei only. Thus the formation of binucleate myocardial cells and nuclear rows is the result of mitoses with impeded cellular divisions. To call these findings examples of amitosis is a misinterpretation.

The karyological basis of atypia.

There is no distinct DNA-pattern correlating with the degree of dysplasia. Atypical DNA-histograms can be found in morphologically normal smears especially when earlier smears had been suspicious. They can also persist after hysterectomy. In cases of progression aneuploidy and large scatter dominate while in cases of regression the DNA values are concentrated in the polyploid classes. Therefore, persisting atypical histograms signalize an increased risk in cases of dysplasia.

Peroxidase activity in human alveolar macrophages demonstrated by 3-amino-9-ethyl-carbazol as substrate.

Airdried smears of routine sputa, bronchial secretions, and bronchus lavages were incubated to demonstrate peroxidase activity in the alveolar macrophages, with 3-amino-9-ethyl-carbazol as substrate. In light microscopic examination two deposition patterns of reaction product could be found: Reaction product only to be found on, resp. in the nuclear membrane; Reaction product deposited in granules throughout the cytoplasm, some cells being totally loaded. However, most of the alveolar macrophages did not show any peroxidase activity. Thus the population of alveolar macrophages comprises resident and exudate forms.

Differential diagnosis of acute allograft rejection and CMV-infection in renal transplantation by urinary cytology.

Acute allograft rejection and CMV-infection are the most common complications after renal transplantation. Quick differential diagnosis between these two complications is still difficult but necessary, since both complications demand a different therapy. More than 2500 urinary samples from 33 transplanted patients were prospectively examined and part of them evaluated quantitatively. Urinary samples of patients with acute renal failure, long-term haemodialysis or immunosuppressive therapy served as controls. The following cytomorphological criteria proved to be useful: Tubular epithelial cells, casts, oxalate crystals (sand-glass shaped), dirty background, increasing erythrocyturia, mixed cell clusters, lymphocytes and mitoses. Rejection is going on when the number of renal tubular cells is increased and two or more further criteria are positive. 25 acute allograft rejections without acute renal failure were diagnosed clinically. All 25 rejections were also diagnosed by urinary cytology. Nevertheless, it is not possible to differentiate between acute allograft rejection and acute renal failure of other origin. CMV-infection was serologically detected in 7 patients. In 6 of them viral infected cells were found in the urine shortly after the onset of unspecific clinical symptoms. Besides the typical "owl-eye" cells milkglass nuclei, sometimes with eosinophilic condensation, were seen while criteria for transplant rejection were never observed at the same time. Cytologic examination of voided urine is a simple diagnostic help for the differentiation between allograft rejection and CMV-infection after renal transplantation.

Pressure induced hypertrophy in the hearts of growing dwarf pigs.

The left ventricles of 8 sibling dwarf pigs were stressed by banding the aorta ascendens for 7 to 49 days. There was no developmental retardation. Neither light nor electron microscopic controls showed signs of insufficiency. 3.7 X 10(7) Bq/kg (1 mCi/kg) body weight (3 H-)methyl thymidine had been applied as pulse at the end of the experiment. The 3 H-index (LI) of the left ventricular wall increases with the pressure registered (r = 0.95). At the same time the values for the right ventricular wall and the left atrium showed an inverse tendency corresponding to the fact that all indices decrease during normal growth. The relation of the indices is two to one for each atrium and its corresponding ventricle, as well as for the stressed left ventricular wall to the right one. The 3 H marked cells are found in groups with constant distances (75-85 microns). High LI are the consequences of the enlargement of these groups. There is no detectable relation to an anatomic structure. Some rare mitoses could be seen, especially in the left ventricular wall. Signs of a high biochemical activity are accumulations of mitochondria, high number of polysomes and large Golgi areas as well as laminas of ergastoplasm. The nuclei are extremely invaginated.

Tetraedric and sand-glass crystals in the urine.

Sand-glass and tetraedric crystals often occur in cytologic evaluations of urinary sediments as a secondary finding. The analyses show inflammation and an increase in protein casts as accompanying changes. The basic diseases are primarily renal but unspecific. The analyses of the crystals by laser-ray-technique (LAMMA-analysis) demonstrate calcium in the positive ionic spectrum in both forms. Differences can be registered in the negative ionic spectrum: sand-glasses and small tetraeders contain considerable amounts of phosphate (PO2- and PO3-), while only the larger tetraedric crystals consist of pure calcium oxalate.

Blind pleural biopsy in combination with cytology of pleural effusions.

The efficiency of a combination of blind pleural biopsy and pleural cytology was examined in a retrospective study of 181 cases observed between 1968 and 1978. The material contained 64 confirmed cases of malignant tumors and 20 of tuberculosis. Of the tumors, 81.3% were diagnosed by one or both methods; 18.7% remained negative. In 53% of the cases, the positive diagnoses corresponded between the two methods; in 26.6% the tumor was found only by cytology and in 10.9%, only by histology. Repeat investigations slightly improved the results with both methods. Reasons for false-negative cytology were bad preservation, fibrosis, nonexfoliative tumors and a mistake of preparation in one case. False-positive results occurred twice in histology, and two cases judged highly suspicious by cytology proved to be clinically negative. In cases of tuberculosis, histologic diagnosis was superior to microbiologic diagnosis.

Nonspecific esterase activity of human alveolar macrophages in routine cytology.

Alpha-naphthyl acetate esterase (ANAE) activity in alveolar macrophages was demonstrated in air-dried smears from samples of 82 sputa, 47 bronchial secretions and 14 bronchial lavages from 113 patients. Enzyme activity was estimated by a semiquantitative scoring method. There was a 7.4% loss of activity after 24 hours of storing the unfixed material, increasing to 14.4% after three days, while storing the air-dried smears for up to four weeks did not change the ANAE activity. The mean cellular esterase activity was correlated to the clinical and cytologic findings. A stringent correlation could be found for patients smoking more than 30 cigarettes a day; they had a 17% increase in activity as compared to nonsmokers. In patients with bronchial asthma, the activity was 18% higher than the total mean. In three patients with pulmonary embolisms, the ANAE activity was also increased. Treatment with a combination of cytostatics and a corticoid caused a severe decrease. No correlation could be found to age, sex, inflammation or malignant or cardiac diseases. These findings indicate that the application of the ANAE reaction to routine cytologic specimens can contribute to the functional characterization of human alveolar macrophages.

Acellular bodies in sputum.

From 70 patients 68.3 +/- 10.1 years of age, 260 sputum specimens containing various acellular bodies were evaluated. This corresponded to 1% of all sputum specimens examined. The round to oval bodies were mostly concentrically structured and displayed different, partly amorphous, partly crystalline components. The periodic acid-Schiff stain was usually positive in these smears, 52% of which contained birefringent bodies. The average diameter was 25 +/- 10.9 micron. While intersample and intrasample frequencies of such bodies were extremely variable, a correlation with an increased number of Curschmann spirals and the degree of inflammation was observed (P less than 0.02). There was a correlation with neither sex, smoking habits nor most types of cancer. A positive correlation existed with chronic obstructive bronchitis, cor pulmonale, obstructive pulmonary diseases and one case of adenocarcinoma of the lung. This finding was confirmed by eight of ten new cases. The formation of the bodies can be intraalveolar, comparable to microliths, in the bronchial glands, corresponding to sialiths, and by intrabronchial mucus condensation, eventually around structures serving as cores. Changing frequencies in repeat investigations demonstrated a presumably rapid formation.

Cytology of the cerebrospinal fluid in primary malignant lymphomas of the central nervous system.

Two cases of primary malignant lymphoma of the central nervous system are reported. Clinical and pathologic findings did not indicate systemic lymphomatous involvement of lymph nodes and bone marrow. The patients presented with different neurologic deficits. Cytologic examination of the cerebrospinal fluid was the first and most useful technique for establishing the diagnosis.

Cerebrospinal fluid and metastasis of transitional cell carcinoma of the bladder.

Two cases are presented of cerebrospinal fluid with tumor cells metastatic from transitional cell carcinomas of the bladder. They demonstrate that in spite of the rarity of transitional cell carcinoma's metastasizing to the central nervous system (0.4% to 0.6%), it is necessary to consider the bladder as the primary site and to obtain urinary cytology in such cases when the primary tumor is still unknown.

Lavage fluid from continuous ambulatory peritoneal dialysis. A model for mesothelial cell changes.

Continuous ambulatory peritoneal dialysis (CAPD) lavage can be interpreted as an artificial short-term ascites. The cellular content of 362 CAPD specimens from 32 patients was investigated. Irregular inflammatory reactions were seen in 85.3% of the specimens and eosinophilia in 27.6%. Mesothelial aggregates of great variability were registered in 59.4% of the specimens and mainly atypical mitoses in 7.5%. The cytologic changes seen in those patients from whom lavage fluids were examined over 10 to 12 months did not correlate with the changes in blood chemistry (BUN and creatinine) in those cases.

Primary malignant melanoblastosis of the meninges. Clinical, cytologic and neuropathologic findings in a case.

A 66-year-old man presented with a six-month history of neurologic symptoms suggestive of a craniospinal tumor or a diffuse inflammatory process in the subarachnoid space. Cytologic examination of cerebrospinal fluid (CSF) revealed inflammatory changes and malignant melanin-containing cells, leading to a diagnosis of meningeal spread of a melanoma. There was no history of skin excisions and no clinical evidence of primary melanoma of the eye. Neuroradiologic investigations, including CT and myelography, to confirm the diagnosis were negative. Despite intrathecal cytostatic therapy, the patient died eight months after the onset of symptoms. Autopsy disclosed diffuse meningeal melanoblastosis of the spinal cord and the base of the brain, confirming the cytologic diagnosis. In addition, two micrometastases in the liver were found as only extraneural manifestation. This case emphasizes the importance of CSF cytology in the diagnosis of diffuse infiltrating processes in the subarachnoid space.