Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under-diagnosed lesion.

Invasive squamous carcinomas of the cervix have traditionally been classified into keratinizing, non-keratinizing, verrucous, warty (condylomatous), papillary transitional (squamo-transitional), and lymphoepithelioma-like carcinomas. The majority of these tumors are easily recognized. We present for the first time the pathological appearances of six cases of invasive squamous carcinoma with growth pattern simulating tangentially cut CIN 3 involving endocervical glandular crypts/clefts. In all cases initial diagnosis on biopsy and/or loop excision was thought to be CIN 3, perhaps with suspicion of early invasion. On further excision and/or on clinical grounds the tumors were frankly invasive. We propose the use of the term squamous carcinoma with "CIN 3-like growth pattern" for such lesions. This is in order to avoid misinterpretation as CIN 3 with subsequent inappropriate management of patients with this type of tumor.

Effect of using templates on the information included in histopathology reports on specimens of uterine cervix taken by loop excision of the transformation zone.

AIM: To determine the change in information relayed from histopathologists to clinicians by using templates for reporting specimens of uterine cervix sampled by loop excision of the transformation zone (LETZ). METHODS: Minimum datasets for the information required from LETZ specimens received from the colposcopy clinic, Royal Infirmary, Edinburgh, were incorporated into templates on the clinical service computer (Pinnacle) of the pathology department, University of Edinburgh. Pathologists completed hard copy versions, which were transcribed into the computer templates for report generation. The effect of the changes on the quality of the pathology reports was studied. The number of cases in which each item in the dataset received comment in template generated reports was compared with that in traditional prose reports compiled before the use of the templates and in prose reports issued after the introduction of the templates. Questionnaire studies were undertaken of clinicians' and pathologists' opinions of the template reports. RESULTS: In the template reports nearly all items received comment in almost 100% of cases. In the prose reports issued both before and after the templates were in use, most items were mentioned in a significantly lower proportion of cases. Clinicians thought the template reports were clearer and the information could be more readily assimilated than from the prose versions. CONCLUSIONS: The use of template reports in these types of specimen allowed more consistent and detailed information transfer. The change appeared to result from the use of the templates rather than from increased awareness of the items to be reported.

Papillary squamotransitional cell carcinoma of the uterine cervix: an advanced stage disease despite superficial location: report of two cases and review of the literature.

Papillary carcinoma of the uterine cervix with features reminiscent of transitional cell carcinoma of urothelial origin is a poorly recognized subtype of cervical carcinoma. This tumour has a propensity for late metastasis and local recurrence in spite of the fact that histologically it could be misinterpreted as cervical intraepithelial neoplasia grade 3 (CIN3) with a papillary configuration or as a squamous papilloma. In this report we describe two examples of papillary squamous/transitional carcinoma of the cervix with literature review. The results indicate that this tumour occurs mainly in postmenopausal women, is potentially aggressive and presents at a more advanced stage inspite of the histological appearance suggesting a superficial or early invasive lesion.

Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas.

Intracytoplasmic mucinous inclusions and lumina have been previously described in non-glandular neoplasms such as urothelial carcinoma. We describe their presence in 93% of non-mucinous ovarian carcinomas. They were found in abundance in all 25 cases (100%) of clear cell carcinoma, in 48 of 50 cases (96%) of serous carcinoma and 20 of 25 cases (80%) of endometrioid carcinoma. The degree of the differentiation of the tumour did not influence the number of inclusions or lumina observed. These results suggest that the presence of intracytoplasmic lumina and mucinous inclusions is more widespread than hitherto appreciated. Their presence in an otherwise poorly differentiated metastatic carcinoma might, at the very last, prompt one to consider the ovary as a possible primary site. In addition, an abundance of intracytoplasmic mucinous inclusion and lumina with microcyst formation, in an otherwise poorly differentiated malignant primary ovarian epithelial tumour, might suggest the possibility of a clear cell carcinoma.

Histological features of CIN3 and their value in predicting invasive microinvasive squamous carcinoma.

AIMS: To determine the histological features in CIN3 associated with or predictive of subsequent microinvasion. METHODS: The histological appearances of CIN3 accompanying 120 cases of microinvasive carcinoma of the uterine cervix were retrospectively studied. Major features were defined as those present in greater than 80% of cases of microinvasive carcinoma (MICA) and less than 10% of control cases of CIN3. One hundred cases of CIN3, 36 showing all, and 64 lacking all, of the major features associated with microinvasion, as defined in the retrospective study, were prospectively studied. Deeper levels were cut to exclude the presence of microinvasion in the original biopsy specimen and negative cases were followed up for a period of up to 18 months in order to assess rates of recurrence or progression. RESULTS: The major features identified in CIN3 associated with microinvasive carcinoma were extensive involvement of surface epithelium and deep endocervical crypts by expansile CIN3, luminal necrosis, and intraepithelial squamous maturation. Other features more commonly present in MICA associated CIN3 than in controls included frequent mitosis and apoptosis, pericryptal concentric fibroplasia, pericryptal inflammatory infiltrate, pronounced cellular pleomorphism, nuclear changes (distinct nucleoli and chromatin clearing), and the emergence of streams of darkly stained spindle cells oriented at right angles to the basement membrane. In the prospective study 83% of cases illustrating the major MICA associated features revealed evidence of MICA or frank invasion either on serial sections of the original biopsy or on subsequent biopsy. None of the 64 cases of CIN3 that lacked these features showed evidence of invasion on serial sections or on further follow up over 18 months. CONCLUSIONS: The data strongly suggest that cases of CIN3 which have a higher probability of association with or rapid progression to invasive disease can be identified. When these features are present in a biopsy specimen of CIN3, serial sections should be performed to exclude the presence of microinvasion. Closer clinical follow up of these patients may be needed.

Hyaline globules in ovarian tumours.

Hyaline eosinophilic globules have so far been described in a restricted variety of tumour types. We have noted their presence in a variety of gynaecological malignancies, in particular mixed Müllerian tumours and other epithelial ovarian tumours. We therefore studied their incidence and distribution in a series of malignant, borderline and benign epithelial ovarian tumours, and endometrial and endocervical adenocarcinomas. Hyaline eosinophilic globules were found in all 30 mixed Müllerian tumours from various sites in the female genital tract, 22 of 30 clear cell carcinomas, seven of 30 serous, two of 30 mucinous, and one of 30 endometrioid carcinomas examined, and were also seen in metastases from these tumours. They were present in only two of 25 borderline serous, one of 25 borderline mucinous tumours, and in four of 50 benign serous and one of 50 benign mucinous tumours. The globules were not found in any of 25 Brenner tumours examined, nor in 30 endometrial or 30 endocervical adenocarcinomas. The globules were periodic acid-Schiff positive after diastase, stained positively with PTAH, and were immunoreactive for alpha-1-antitrypsin. This study therefore demonstrates that eosinophilic globules are not specific for any particular tumour. However, their frequency in malignant mixed Müllerian tumours suggests that this diagnosis should be carefully excluded whenever these globules are present in epithelial tumours of the female genital tract.

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in the uterine cervix and cervical squamous neoplasia.

This is a retrospective study, in which PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was used in the assessment of 20 cases of FIGO stage IB cervical carcinoma, 30 cases of CIN, 10 cases of koilocytosis and 20 cases in which the transformation zone was histologically normal. The results showed that in the normal transformation zone the proliferative compartment was confined to the first 1-2 suprabasal cell layers. In CIN the pattern of staining corresponded to the grade of the lesion. In viral wart lesions occasional koilocytes demonstrated strong nuclear staining. In all cases of stage IB cervical carcinoma the PC10 index was high, irrespective of tumor grade response to treatment.

Accuracy of cervical smears in predicting the grades of cervical intraepithelial neoplasia.

This is a retrospective study carried out to assess the correlation between the cytology and histology of cervical intraepithelial neoplasia in 1325 women. A poor correlation between the cytologic and histologic diagnosis of the various grades of CIN was shown. Forty-one percent of smears with repeated borderline change and 50% of those predicting CIN1 showed a higher grade of CIN on histology. The overall apparent false negative rate of cervical smears for high grade CIN (CIN2 and CIN3) was 19% and for CIN3 alone was only 3%. It is therefore concluded that there is a consistent tendency for cervical cytology to underestimate the severity of histologic lesions and it is therefore important that the clinicians ensure adequate follow-up of patients whose smears show a lesser degree of abnormality.

Ceroid granuloma of the uterine cervix.

An excision biopsy was taken from a 59-year-old woman with a small dark-brown lesion on the anterior lip of the cervix. The histology revealed an ulcerated surface epithelium with a band-like infiltrate of pigment containing macrophages in the subepithelial zone. Histochemical examination of the specimen revealed that the pigment was ceroid. This is, to the best of our knowledge, the first case report of ceroid granuloma of the uterine cervix.

Benign vaginal polyp: a histological, histochemical and immunohistochemical study of 20 polyps with comparison to normal vaginal subepithelial layer.

Twenty benign vaginal polyps from 18 patients, together with sections from normal vaginal epithelium, were studied histologically, histochemically using elastic van Gieson stain and immunohistochemically using monoclonal antibodies against vimentin, desmin and actin. The striking finding was the similarity, both histologically and immunohistochemically, of the stroma of vaginal polyps to that of the loose subepithelial layer found in normal vagina. The important difference was the marked degeneration of the elastic tissue, increased number of stellate and giant fibroblasts and subepithelial condensation of fibroblasts in the polyps. These findings support the hypothesis that vaginal polyps may represent a reactive hyperplasia of the loose subepithelial zone of the vaginal wall.

Mild cervical intraepithelial neoplasia (CIN 1): a histological overdiagnosis.

This study was undertaken to assess whether mild cervical intraepithelial neoplasia (CIN 1) lesions are histologically overdiagnosed and, if so, what the possible reasons are for this. The magnitude of the discrepancy between the histological diagnosis of CIN and corresponding smear results was also investigated. Between January and April 1988, 282 patients were found to have a histological diagnosis of CIN 1. The cervical smear result was negative in 42% of cases, borderline in 14% and in the remaining 44% various grades of CIN were predicted. Review of both cytology smears and histology sections was undertaken to identify reasons for this discrepancy. The results suggest that: (1) there is a tendency among histopathologists to overdiagnose cases of CIN 1, as occurred in 10% of cases in this study: (2) even if strict morphological criteria are followed, there will always be cases where histopathologists are uncertain whether a lesion is CIN 1 or some reactive process--for these cases, 22% in our study, the term borderline is recommended; and (3) cervical smears may give false negative results, as in 35%, 18% and 3% of our cases of CIN 1, CIN 2 and CIN 3 respectively.

Cutaneous ciliated cyst: a case report and immunohistochemical comparison with fallopian tube.

An example of a cutaneous ciliated cyst in the buttock of a 42 year old woman is reported. The histological and immunohistochemical features of the cyst are presented: comparisons with fallopian tube are made and this rare lesion is discussed.

Epithelioma cuniculatum plantare.

The clinical and histological findings and treatment of three patients with this well differentiated squamous cell carcinoma of the foot are presented.

Verruciform xanthoma of the skin.

A case of verruciform xanthoma is described, representing the fourth case of an extraoral lesion and the first case of xanthoma of this type to involve the true skin. The differential diagnosis from other types of xanthoma, and from granular cell tumour, verrucous carcinoma and other lesions is discussed. This lesion is well known to oral pathologists but deserves wider recognition by histopathologists in general.

Cell kinetics in the mouse small intestine during immediate postnatal life.

The cell proliferation kinetics in the small intestine of newborn Balb/c mice were studied, from day 1 through to day 21 after birth. The size of the functional compartment and the proliferation compartment was determined as well as the cell production rate in the crypt using the micro-dissection technique combined with metaphase arrest method. The effect of weaning on cell proliferation was studied. The results suggest that: (1)There is continuous increase in cell proliferation and in the size of the functional and proliferative compartment over the 21 days. (2) The cell proliferation proceeds at a slower rate than in adult animals. (3) There is a sharp increase in cell production rate during the third week of postnatal life. (4) The cell proliferation was faster in conventionally weaned litters than the non-weaned group. (5) The intestinal mucosa in newborn mice is not in a steady-state conditions as in adults; cell production rate exceeds cell loss.

The effect of epidermal growth factor (EGF) on cell proliferation of the gastrointestinal mucosa in rodents.

The effects of epidermal growth factor (EGF) on the cell production rate throughout the gastrointestinal mucosa in adult rats and mice was studied. The vincristine arrest technique combined with the micro-dissection method was used to estimate the cell production rate in the crypt. EGF showed trophic effects on some parts of the bowel, viz. duodenum, jejunum, ileum (5%, 50%, 95% along the bowel length respectively) and colon. But is showed no effect on the cell production rates in the gastric glands. The response to EGF differed in rats and mice and at different times after the injection. EGF stimulates cell proliferation in the duodenal and ileal crypts in mice, and the jejunal and ileal crypts in rats 16 h after injection. On the other hand, EGF stimulates colonic crypt cell proliferation only, in mice 8 h after injection.

Circadian rhythm in the rate of cellular proliferation and in the size of the functional compartment of mouse jejunal epithelium.

Circadian variation in the small bowel mucosa of male Balb/c mouse was studied. The labelling was studied at 2 hourly intervals throughout a 24 h period by using autoradiographic techniques with 3HTdR. A 12 h light-dark schedule was employed. Villus and crypt cell populations, together with the mitotic index, were studied using the micro-dissection technique. Growth fractions were determined from the labelling index distribution curves. The peaks in both villus and crypt cell population occurred during the day, with maximum villus population of 3,887 cells/villus at 13.00 h and maximum crypt population of 178 cells per crypt at 09.00 h. The peaks of labelling index (Is) and mitotic index (Im) occurred during the dark period. The peak value of Is 38% at 17.00 h-19.00 h, was about 6-8 h in advance of the peak value of Im (6%). The peak in growth fraction corresponded to that of the labelling index.