[Cytodiagnosis of benign, precancerous and malignant skin changes]. / Beitrag zur Zytodiagnostik benigner, präkanzeröser und maligner Hautveränderungen.

Smears of the keratinizing squamous epithelium were taken from various parts of the body of 252 patients. The conditions sampled were 28 inflammatory lesions, 51 benign tumors, 31 mildly precancerous lesions, 34 seriously precancerous lesions, 42 basal cell carcinomas, and 38 squamous cell carcinomas. In addition, we examined smears of 28 healthy controls. The specimens were evaluated according to cytomorphological criteria of malignancy previously described for vulvar lesions. We made use of a modified Papanicolaous's classification. About 18% of the benign lesions proved falsely positive; 16% of the mildly precancerous lesions, 3% of the seriously precancerous lesions, and 3% of the invasive carcinomas proved falsely negative. The material collected was insufficient for diagnosis in about 10% of the cases. Aside from punch biopsy, the cytological investigation of cutaneous lesions may be a valuable technique regarding the early diagnosis of cancer and precancer of the skin.

Structural and morphometric analysis of parakeratotic and dyskeratotic cells exfoliated from various vulvar lesions. Correlation with data from cervical cytology.

Smears were taken from the vulvar skin of 123 patients (21 with normal-appearing skin and 12 with dystrophic, 29 with benign, 20 with precancerous and 53 with malignant conditions). In each case, 20 nucleated horny squames with the highest visible degree of abnormality were identified in the smear. The cytoplasmic and nuclear structures of these cells were analyzed, and the cytoplasmic and nuclear perimeters were measured by a graphics tablet (digitizing board) equipped with a camera lucida system. Five cytomorphometric parameters were calculated: cytoplasmic and nuclear areas and shape factors and the relative nuclear area. A stepwise multivariate discriminant analysis was used to evaluate the statistical significance of the parameters. Structurally, the cells from different vulvar conditions did not differ much from each other except in the formation of small cellular projections ("pseudopodia"), which were found significantly more frequently in precancerous and cancerous lesions than in others. Nuclear degeneration was a general finding in all examined cases of all conditions. Morphometric analysis revealed cytoplasmic pleomorphism to be the predominant feature associated with increasing degrees of malignancy. There was no significant increase in the relative nuclear area with increasing malignancy because the cytoplasmic and nuclear areas enlarged almost simultaneously. The cellular features found in nucleated horny cells exfoliated from various vulvar lesions are quite different from the well-known attributes of squamous epithelial cells originating from comparable conditions of the uterine cervix.

Current vulvar diagnostic methods, with special reference to vulvar cytology.

The established noninvasive procedures for early detection of vulvar cancer failed in the past, probably because they were based on indirect criteria for malignancy. Exfoliative cytology, however, is the only method that is able to identify specific morphologic features although completely different from the well-known features of cervical cytology. A smear should be taken, therefore, from every vulvar lesion. Using all the relevant diagnostic methods, including punch biopsy, should lead to an improvement in early vulvar cancer detection.

Cytologic and histologic observations on the sex hormone dependence of the vulva.

The usefulness of vaginal cytology in the assessment of hormonal function is well accepted. Our study established that the epithelial horny cells exfoliated from the vulvar skin also exhibit morphologically visible signs of hormonal activity. Cytologic analysis of 429 vulvar smears from 174 women during 88 cycles and postmortem histologic examination of vulvar specimens from an additional 65 women showed parakeratotic keratinization to be significantly more frequent premenopausally than postmenopausally. A vulvar "parakeratotic index" was developed that fluctuates along with the well-known eosinophilic and karyopyknotic indices of the vagina and corresponds to the plasma estradiol concentrations during the cycle. Administration of estrogens in postmenopausal women initiates a striking increase in the index, which is otherwise quite low during that phase of life.

[Exfoliative cytology of the vulva. Histological and clinical aspects]. / Die Exfoliativzytologie der Vulva. Histologische und klinische Gesichtspunkte.

Special criteria of malignancy are evident in vulvar cytology which are completely different from the well-known features of cervical cytology. These criteria are well suited to improve the efficiency of vulvar cytology. Cytology and the full utilization of all other diagnostic procedures should lead to the early detection of precancerous and cancerous lesions of the vulva.

[Quantitative and qualitative structure analysis of cell exfoliated from the normal vulva and from benign, precancerous and malignant vulvar lesions]. / Quantitative und qualitative Strukturanalyse der bei normalen, benignen, präkanzerösen und malignen Vulvaläsionen exfoliierten Zellen.

The value of cytological smears for screening for cancer of the external female genital organs has been stressed recently on repeated occasions. The evaluation of the cornified cells obtained from different vulvar diseases has however only been undertaken by subjective criteria. The qualitative structural analysis and the planimetric evaluation of 3,260 cornified cells from 123 patients with vulvar lesions of different types showed fundamental and essential differences in the criteria of malignancy compared to cytology of the uterine cervix. Whereas the nuclear plasmatic ratio and the chromatine structure are of secondary importance, the absolute size of the nucleus and the cell and especially the degree of cytoplasmatic polymorphy have a high degree of cytoplasmatic polymorphy have a high degree of importance. The special cytomorphological criteria described permit the differentiation of benign and malignant lesions of the vulva from the cytology of the cornified cells.

[Cytologic and histologic studies of hormone dependence of the skin of the external female genitalia]. / Zytologische und histologische Untersuchungen zur Hormonabhängigkeit der Haut des äusseren weiblichen Genitales.

The value of vaginal cytology for functional hormonal diagnosis is generally recognized. Largely unknown was that the cornified cells obtained from the skin of the vulva likewise show morphologically demonstrable signs of hormonal effects. The cytological analysis of 429 cytological smears of the vulva obtained from 174 women during 88 cycles and the histological analysis of excisions of the vulva obtained at 65 female autopsies showed that the parakeratotic type of cornification is significantly more frequent in the premenopause than in the postmenopause. During the menstrual cycle a parakeratosis index can be identified which is parallel to the well known eosinophilic and karyopyknotic indices of cytological smears from the vagina and corresponds as well to the cyclic levels of estradiol in the serum. Exogenous administration of estrogen during the menopause results in a drastic increase of the parakeratotic index which is normally low following the menopause. These observations show that not only the uncornified squamous epithelium of the vagina but also the cornified squamous epithelium of the vulva reacts to endogenous and exogenous hormonal stimulation although in a different pattern.

Significance of the morphology of anucleated squames in the cytologic diagnosis of vulvar lesions. A new approach in diagnostic cytology.

Vulvar smears from 80 patients with various vulvar lesions were analyzed. In each case, 10 anucleated horny squames were identified and the perimeters measured by a graphic tablet (digitizing board) equipped with a camera lucida system. The internal computer of the system calculated areas and shape factors, with the latter characterizing the degree of cellular pleomorphism.

[Cytologic cancer prevention in the vulva. Morphologic study of an extensive case material]. / Die zytologische Krebsvorsorge am äusseren weiblichen Genitale. Morphologische Studie an einem grossen Untersuchungsgut.

464 patients, 286 healthy patients and 178 patients with lesions of the vulva had cytological and/or histologic examinations of the vulva. The normal vulva sheds in approximately 50% of the cases anucleate squames and in approximately 50% of the cases parakeratotic cells. In benign lesions of the vulva, in 1/3 of the cases each one finds either and anucleate squames, parakeratotic cells or mildly dyskariotic cells. In premalignant lesions 1/2 of the cases exfoliate mildly dyskariotic cells and the other 1/2 severely dyskariotic cells. In carcinoma of the vulva cytologic evidence of cancer is found in approximately 60% of the cases whereas 34% of the cases only show severely dyskariotic cells and 6% only mildly dyskariotic cells. Ulcers and defects do not increase the yield of exfoliated tumour cells. Exfoliative cytology of the vulva is considered to be an important part of the early diagnosis of cancer of the vulva.

Cytology of the exfoliative layer in normal and diseased vulvar skin: correlation with histology.

The vulvae of 464 patients were studied by cytologic and/or histologic examination. Of these, 286 patients had clinically normal vulvae and 178 patients, diseased vulvae. Histology revealed 47 benign, 20 precancerous and 111 malignant lesions. Structural variations of the vulvar stratum corneum could be classified into five categories: orthokeratosis, hyperkeratosis, parakeratosis, dyskeratosis and tumor penetration. Orthokeratosis, hyperkeratosis and parakeratosis were present in the normal vulvae as well as in benign conditions; they were characterized cytologically by anucleated horny squames or by parakeratotic cells. Dyskeratosis usually indicated precancerous or malignant conditions but was also observed, although in mild form only, in certain benign lesions, e.g., acute inflammation and condyloma acuminatum. Nevertheless, evidence of dyskeratotic cells in vulvar smears should cause concern because vulvar cancer frequently is covered by a continuous horny (dyskeratotic) layer. Only half of the malignant vulvar lesions showed tumor penetration through this superficial layer, with subsequent exfoliation of tumor cells.

[Diagnosis of vulvar diseases. 2. Discussion and conclusions for practice]. / Vulva-Diagnostik. Teil 2: Diskussion und Schlussfolgerungen für die Praxis.

Dystrophic vulvar conditions are found to increase with age and to predominate in postmenopausal women. The differentiation of this entity from infectious lesions and from precancerous conditions by clinical examination is extremely difficult. Therefore, diagnostic procedures are necessary which supplement local inspection and palpation. Photography is useful for documentation and follow-up control and colposcopy is suited for examination of lesions exhibiting erythroplakia, but not for leukoplakia which is much more frequent. Exfoliative cytology occupies a key position in vulvar diagnosis, since negative findings almost rule out a precancerous process, so long as the criteria of malignancy are sufficiently extended to include all abnormalities of the horny cells. Infections frequently cause equivocal cytological findings which disappear after appropriate treatment. Such infections can be diagnosed by phase contrast cytology, cultures, or serological tests. In many cases, further investigation will reveal diabetes mellitus or other metabolic disorders (internal consultant), urinary incontinence (urological consultant), allergic dermatoses (dermatological consultant) or psychoneurotic disease (neurologic consultant). Positive cytological findings always prompt biopsy; but equivocal and negative findings will also lead to histologic examination, if repeated control reveals constancy or exacerbation of a lesion in spite of the use of different diagnostic and therapeutic procedures. Vital staining with the toluidine blue method (so-called Collins test) is well suited for marking para- or dyskeratotic skin areas which then can be removed by surgery.

New aspects of vulvar cytology.

Smears were taken from vulvar skin in 203 cases (83 normal-appearing, 23 benign, 12 precancerous and 85 malignant conditions). Three cases were analyzed by electron microscopy. The appearance of dyskeratotic cells was regarded as a sign of malignancy; this was supported by ultrastructural study. Smears from normal vulvar skin revealed a high correlation between age and presence of nucleated keratinized squames, which occurred most often in the third and rarely in the eighth decade. Benign conditions showed cellular features like those of the normal vulva. In precancerous lesions, 58% of the smears showed dyskeratotic cells. Malignant conditions showed dyskeratotic cells in 66% of the smears and true cancer cells exclusively in an additional 14%. Our observations indicate that vulvar cytology can be a major diagnostic aid in all suspicious cases, especially in the elderly. Vulvar cytology cannot replace an exact histologic examination, but it can provide a reason for taking a biopsy earlier than might otherwise be the case.

[Definition of the terms "parakeratosis" and "dyskeratosis" from gynecocytological point of view (author's transl)]. / Zur Definition der Begriffe "Parakeratose" und "Dyskeratose" aus gynäkozytologischer Sicht.

In dermatopathology, parakeratosis and dyskeratosis have always been regarded as exactly defined terms. However, in keratinizing lesions of the portio and vagina, and especially of the vulva, atypical changes have repeatedly been described both within the unkeratinized squamous epithelium and within the stratum corneum. These observations were confirmed by a combined cyto-histological study of the vulva in 464 women. A graduation of cellular atypias was possible. The question therefore occurs as to whether the usual terms para- and dyskeratosis should be supplied with certain additional denotations, or whether they should be sub- or newly classified. Several pathophysiological and etymological considerations would make a new classification seem advisable.

[Localization of sclerotic lesions in the coronary arteries and their epicardial branches (author's transl)]. / Untersuchungen über die Lokalisation sklerotischer Veränderungen in den Koronararterien und ihren grossen epikardialen Asten.

In the hearts of 100 unselected adult autopsies (average age 65 years) the coronary arteries and their major branches were investigated. After opening the lumen, the vessels were measured, and the location of all sclerotic lesions was identified, including fatty streaks. The frequency of distribution of advanced sclerotic changes was similar to that of lipid and fibrolipid plaques. 1003 major coronary artery branches were studied. 25% of them showed sclerotic changes in contrast to 92% in the coronary arteries themselves. There was a good correlation between the sclerotic lesions in the coronary arteries and their branches: no changes were found in the branches the corresponding stems of which were unchanged. In contrast to that, sclerotic branches nearly always originated from sclerotic areas of the coronary arteries. Branches of the left anterior descending artery were more frequently affected by atherosclerosis (39%) than branches of the right coronary artery (17%). Contrary to the right coronary artery sclerotic changes of the proximal branches of the left anterior descending and the left circumflex artery were significantly more frequent than sclerotic lesions of the distal branches. The frequency of sclerotic lesions in the branches was similar to that in the coronary arteries; the proximal part was more frequently affected than the distal one. In addition, the peripheral decreasing frequency of sclerotic changes, which was found to be more pronounced in the left coronary arteries than in the right one, showed a similar behaviour in the corresponding branches. Our investigations indicate the vessel's diameter to be a significant (but not the only) factor in atherosclerosis development in coronary arteries and their branches. In case of a corresponding size of lumen, the frequency of sclerotic changes in the coronary arteries was approximately the same as in their branches.

[Bilateral retro- and subauricular fistulae with eversion of the epithelial lining (author's transl)]. / Doppelseitige retro- und subaurikuläre Fisteln mit Ektropium des Fistelgangepithels.

An infant with multiple congenital anomalies was observed: bilateral cleft lip and palate, left cystic kidney, bilateral retroauricular fistulae with ectropion of the epithelial lining. These fistulae ended in tissue of thymus. They are derived from the ductus thymopharyngicus. In this case a large ectropion was constated on both sides, which was in this form not described before. The early case history, the therapy and the rare histological findings are described and the up to date unknown abnormality with figures represented.