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BACKGROUND: Granular cell tumors are neoplasms of uncertain histogenesis, although a neural origin is favored. Most reports on the cytologic features of granular cell tumors have been on lesions from the breast or respiratory tract. However, there are only a few reports on fine needle aspiration (FNA) cytologic diagnosis of cutaneous or soft tissue granular cell tumors. CASE: A 7-year-old girl presented with a skin lesion on her right forearm of one year's duration. The FNA smears showed sheets and clusters of oval to polygonal cells with an abundant amount of granular cytoplasm. Many single, scattered cells with similar morphology were seen in the background. Immunostaining for S-100 protein showed granular cytoplasmic positivity. The tumor was diagnosed as a benign granular cell tumor. The histopathology report on the excised lesion confirmed the FNA diagnosis. CONCLUSION: The cytopathologic features of granular cell tumors presenting as skin lesions are distinctive enough to allow a correct diagnosis on FNA cytology.

Objectives: To study the distribution of human papillomviruses (HPV) in women in Kuwait using hybrid capture assay and their correlation with the severity of cervical lesions based on cytological diagnosis and to establish the relationship if any between the quantity of the viral load and the degree of severity of cervical lesions. Methods: Study sample included 181 women in the age range of 20–68 years, attending the Out-Patient Department of Gynaecology of the Al-Farwaniya Hospital and six polyclinics in Kuwait during the years 1997–1998. Cervical smears were interpreted according to the modified Bethesda System. HPV DNA was detected using a chemiluminescent-based Digene hybrid capture assay. Results: Of the 181 women studied, the cytodiagnosis was as follows: normal and inflammation 139 (76.8%), atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS) 26 (14.4%) and squamous intra-epithelial lesion (SIL) 16 (8.8%). High-risk HPV DNA had a very low prevalence in women with normal and inflammation cytology, i.e. 1.4% in contrast to women with SIL lesions which had a positivity of 68.8%. ASCUS and AGUS group had 7.7% high-risk HPV DNA positivity. The quantity of viral load was directly related to the increase in the severity of the lesions. Conclusion: High-risk HPV DNA was detected in a significantly higher proportion of women with SIL lesions as compared to those with normal cytology (p < 0.0001). Furthermore, the viral load of high-risk HPV DNA was directly related to the severity of the cervical lesions, relative light unit ratios being >20 in the majority of SIL lesions.

FNAC is a simple diagnostic tool for the initial evaluation of various deep seated pathological lesions. This study describes the applicability and practical aspects of the technique in establishing the diagnosis of spinal tuberculosis (TB) with the aid of radiographic guidance. The study was conducted in a major teaching hospital in Kuwait between the years 1985 and 1994. Twenty-nine patients (M:F = 18:11 and age range 8-72 years) with clinically and/or radiologically suspected spinal TB were seen in the Department of Cytology, Mubarak Al Kabeer Hospital. The patients were re-examined by either computed tomography (CT) scanning (n = 19) or fluoroscopy (n = 10) to localize the lesion for FNAC. FNAC smears were routinely stained with Papanicolaou and Diff Quik stains and one smear of each case was stained with Ziehl-Neelsen (Z-N) stain for acid-fast bacilli (AFB). Aspirated purulent material or syringe washings of dry aspirates were also submitted for microbiological cultures including AFB. Radiological and cytological findings were recorded in each case. Radiological findings included: bony rarefaction and destruction (93.1%), narrowed disc space (89.7%), soft tissue calcification (65.5%) and para-vertebral abscess formation (51.7%). Cytological findings included: epithelioid cell granulomas (89.7%), granular necrotic background (82.8%) and lymphocytic infiltration (75.9%). Smears were positive for AFB in 51.7% of cases. A positive AFB culture was obtained in 82.8% of cases, including all cases with positive AFB on smear by Z-N stain. Radiologically guided FNAC with AFB culture is a simple, reliable and practical approach to diagnosing spinal TB lesions. With a high diagnostic yield, it allows immediate initiation of specific treatment, helps to avoid invasive diagnostic procedures, and decreases hospitalization time.

Background. The role of male behavior in the genesis of cervical cancer was examined. In India, where the incidence of cervical cancer is among the highest in the world, promiscuity among women is virtually unknown. In this study, the authors investigated the role of male behavior in cervical carcinogenesis among Indian women who had one lifetime sexual partner. Methods. A case-control study was used. Results. Premarital sexual relationships (relative risk [RR], 1.9; confidence interval, 1.2–3.2) and extramarital sexual relationships (RR, 2.7; confidence interval, 1.5–4.9) of husbands were risk factors. When husbands had sexual relationships both before and during the marriage, their wives' risk of getting cervical cancer increased by 6.9 (CI, 2.3–20.7). Risk also increased with husbands having three or more extramarital sexual partners (RR, 3.05; CI, 1.25–12.6). Sexual contact with prostitutes before or after marriage, however, did not increase the risk. History of sexually transmitted disease before marriage (RR, 2.9) or after marriage (RR, 5.9) was an important risk factor, which persisted after controlling for other factors. Sexual abstinence for 40 or more days after a wife's giving birth or having an abortion provided protection. Sex with uncircumcised men or men circumcised after age 1 year increased the risk of cervical cancer (RR, 4.1). Bidi smoking (bidi is a cheap smoking stick of 4–8 cm, consisting of a rolled piece of dried temburni leaf [Diospyres melanoxylon] containing 0.15–0.25 g of coarsely ground tobacco) for more than 20 years was a significant risk factor (RR = 2.4), whereas cigarette smoking was not a risk factor. Conclusions. Male sexual partners play a role in cervical carcinogenesis.

Background. Infection with human papillomavirus (HPV) is considered to be the principal causal agent in the development of squamous cell carcinoma of the uterine cervix. Although adenocarcinoma of the cervix originates adjacent to the squamous epithelial neoplastic lesions, the etiopathogenesis of adenocarcinoma is not yet clearly understood. Recent studies have raised more controversy, rather than answering the question of whether specific HPV infection also plays a role in the development of adenocarcinoma of the cervix. Molecular DNA hybridization techniques were used to detect HPV types prevalent in both adenocarcinoma and squamous cell carcinoma of the uterine cervix, which is the most common cancer in Indian women. Methods. Histologically confirmed, formaldehydefixed, paraffin-embedded tissue sections from 12 cases of adenocarcinoma and 30 cases of squamous cell carcinoma of the uterine cervix were analyzed retrospectively for the presence of HPV DNA types 6b, 11,16, and 18 by both Southern blot hybridization and in situ hybridization. Of 12 adenocarcinomas, 5 (41.67%) tumors were positive for HPV DNA. All five cases were positive for HPV 16, and two (16.6%) of these were hybridized again to the HPV 18-specific DNA probe. All tumors were negative for HPV 6b and 11. In addition, no biopsy specimens were positive after hybridization with a mixed probe of HPV 31, 33, 35, 39, and 45. These results were compared to those obtained for 30 squamous cell carcinomas of the cervix. Although 20 (66%) were exclusively positive for HPV 16 and 6 (20%), more tumors were of HPV 16 related types as detected under nonstringent conditions of hybridization, only one (3%) was positive for

BACKGROUND: Langerhans cell histiocytosis (LCH) of the thyroid is a rare condition, and fine needle aspiration cytology (FNAC) of this entity has rarely been described. CASE: FNAC was done on a 3-cm-diameter thyroid swelling in the left lower lobe of the thyroid gland. Smears showed a large number of lymphocytes, eosinophils, thyroid follicular cells and discrete, large cells with prominent nuclear grooves. Mitotic activity was frequent. A cytologic diagnosis of LCH was offered. Subtotal thyroidectomy was performed, and the cytologic diagnosis was confirmed by histology. CONCLUSION: LCH of the thyroid has certain salient diagnostic features. The presence of histiocytes with prominent nuclear grooves, reactive lymphoid cells and eosinophils along with benign thyroid follicular cells should raise the suspicion of this rare entity on FNAC smears of the thyroid.

BACKGROUND: Fine needle aspiration cytology (FNAC) of extranodal non-Hodgkin's lymphoma of the tongue has rarely been described. CASE: A 47-year-old male was referred to the cytology laboratory for FNAC of a 3-cm-diameter swelling on the dorsum of the tongue, with a primary clinical diagnosis of soft tissue tumor. FNAC smears showed discrete, monomorphic, round to oval cells with scanty, deep blue cytoplasm. The nuclear margin was regular, with occasional prominent nucleoli and fine nuclear chromatin. The background showed many lymphoglandular bodies. The cells were strongly positive for leukocyte common antigen. A cytologic diagnosis of high grade non-Hodgkin's (NHL) was offered and subsequently confirmed by histopathology. CONCLUSION: Primary NHL of the tongue is relatively rare. As there are no characteristic clinical features of extranodal NHL of the tongue, FNAC may be useful for rapid diagnosis and management of such cases.

The peripheral blood lymphocyte subpopulations in Indian women with various grades of cervical intraepithelial neoplasia [33], invasive cancer [22] and matched controls [30] were studied using specific monoclonal antibodies and biotin avidin immunofluorescence technique. Our results showed a significant fall in peripheral T (CD2) B(CD22) cells in patients with CIN III and invasive cervical cancer lesions compared to controls (P less than 0.001). Similarly the quantum of T helper cells (CD4) decreased according to the severity of cervical lesions (P less than 0.01 - P less than 0.001), whereas the T suppressor cells (CD8) depicted an increasing trend in patients with higher grade of cervical lesions (CIN III and invasive cancer, P less than 0.001) as compared to controls. Further, the CD4/CD8 ratio showed a significant downfall with the severity of cervical lesions (P less than 0.01 - P less than 0.001), indicating a perturbance in the homeostasis of host cellular immunity.

In a study of factors related to cervical carcinogenesis, a cohort of 1,107 cervical dysplasia along with 1,077 controls matched for age and parity were followed up prospectively. During the follow up 75 dysplasia cases progressed to carcinoma in situ. The overall rate of progression of dysplasia to malignancy was observed to be 15.7% at the end of 108 months of follow-up. The analysis of progression rates in relation to various factors revealed significantly higher progression rates for initially higher grade of dysplastic lesions, and early age at consummation of marriage (ACM). The other factors, such as religion, literacy status of the patient, number of pregnancies, presence of cervical erosion, history of fetal loss and positivity to HSV-II antibodies, did not reveal statistical significance. The case-control comparison for detection of HPV 16/18 by in situ hybridisation revealed the presence of HPV 16/18 sequences in 67.3% of the dysplasia subjects progressed to carcinoma in situ while 27.3% of precancerous cases regressed to normalcy. The difference was found to be statistically significant (P less than 0.001).

OBJECTIVE To compare ThinPrep (TP) Papanicolaou smears (Cytyc Corp., Box-borough, Massachusetts, U.S.A.) with matching conventional Papanicolaou (CP) smears for specimen adequacy, cytologic quality, diagnostic accuracy and screening time. STUDY DESIGN In this prospective study of 1,024 women a split-sample, matched-pair design in favor of CP slides based on single-blind criteria was followed with a smear on a glass slide for CP and the remaining material collected in Preserv-Cyt solution (Cytyc) for a TP smear. A Cytobrush (Medscand, Hollywood, Florida, U.S.A.) was used for smear preparation for CP. TP smears were processed in ThinPrep 2000 (Cytyc). Smears were stained with Papanicolaou stain and were interpreted according to the Bethesda system. RESULTS The number of satisfactory but limited (SBL) cases with TP were 77 (7.5%) as compared to 127 (12.4%) with the CP method. This reduction in SBL smears with the TP method and consequent increase in satisfactory smears were highly significant (P < .001) by McNemar's test. As regards unsatisfactory smears in discordant pairs, although the number of unsatisfactory smears was higher with TP (41 cases) as against CP (27 cases), the difference was not statistically significant (P < .05). The split-sample method showed a high correlation between the CP and TP diagnoses. TP smears had a significant advantage over CP smears in the reduction in the number of ASCUS and AGUS cases (14 vs. 29) (P < .05) and increased the pickup rate of LSIL, 6 vs. 1. Time taken to screen the TP smears was half that of CP smears. No cases of LSIL or HSIL were missed on TP smears. CONCLUSION The liquid-based processor significantly improved the adequacy and quality of smears, resulting in fewer recall cases for SBL smears, leading to more definitive diagnoses in atypical cases, increasing the pickup rate of LSILs and reducing the screening time. A machine handling multiple specimens automatically would decrease cost and be an asset to a cytopathology laboratory.

An attempt has been made to study the correlates of knowledge of cervical cancer in a community. The survey undertaken is a part of Knowledge, Attitude and Practice (KAP) study prior to initiation of cytological screening. Total women interviewed by KAP survey were 1411 selected through 2 stage stratified random sampling. Subjects for the present analysis consisted of a group of women who had reported previous gynaecological problems related to cervical cancer. The study brought out that younger women had better awareness and knowledge about cervical cancer and related information. Literacy status for education and exposure to family planning was influential in creating awareness about cervical cancer. Lastly, the earlier episodes of gynaecological problems, and treatment seeking behaviour lead to higher awareness (efforts may be made to innovate ways to reach older and illiterate women at risk of cervical cancer for better awareness in the community.Data were collected from a community-based cytological screening program tested by Maulana Azad Medical College (MAMC), Delhi, India, in order to utilize the health infrastructure for prevention, detection, and management of cancerous lesions of the cervix and to establish a community referral system for control of cervical cancer. The Alipur Primary Health Center field practice area of MAMC provides health care to 65,000 people in 27 villages. 609 (42.2%) of the total of 1411 women interviewed reported previous incidence of gynecological problems, but only 281 had sought treatment. 36.3% of those who reported earlier gynecological problems and 40.2% of those who sought treatment, as compared to 30.8% of all the women interviewed, were aware about cervical cancer in general. The literacy status and ever use of family planning was significantly (p .05) associated in all groups with the awareness of cervical cancer, earlier episodes of gynecological problems, and seeking treatment. Among women aged less than 35 years, who were informed about cervical cancer, there were statistically significant differences (p .5); these were 31.1% of all the women interviewed, 33.8% of those who reported earlier gynecological problems, and 43.9% of those who sought treatment for earlier gynecological problems compared to women aged 35 years and above (P 0.05). Only 114 out of 221, who were informed and who reported gynecological problems, sought treatment (acceptors). Non-acceptors of treatment in this group lacked correct knowledge about cervical cancer. 34.5% of acceptors knew about the age of onset, 11.4% about early symptoms, and 24.8% about the method of early detection compared to 30.6%, 0.0%, and 3.7% of non-acceptors, respectively. 68.5% of the non-acceptors had obtained information regarding cervical cancer from relatives, neighbors, and friends, while the acceptors had obtained the information from hospitals and mass media also. 60.2% of acceptors were exposed to family planning compared to 50.9% of non-acceptors.

To find out the gross and microscopic differentiating features between nipple discharges (ND) due to various breast lesions, smears of 602 ND samples from 484 cases were reviewed by one of the investigators (D.K.D.). The reviewed cytodiagnoses were as follows: benign nipple discharge (59.1%), inflammatory ND (6.5%), ?papillary lesions (2.5%), papillary lesions (20.6%), papillary lesions with atypia (3.8%), duct cells with atypia (0.2%), suspicious for malignancy (0.5%), malignant ND (1.2%), and inadequate (5.6%). Following review, samples with epithelial abnormalities (?papillary lesion, papillary lesion with and without atypia, duct cells with atypia, suspicious for malignancy, and malignancy) increased from 16.6% to 30.4% of adequate samples (P < 0.0001). 37.9% unilateral ND samples showed epithelial abnormalities, as opposed to 18.9% of bilateral ND samples (P < 0.0001). Bloodstained ND showed epithelial abnormalities in 41.5% samples, as compared to 22.1% of ND with other specified gross characteristics (P

OBJECTIVE: To compare the various cytologic features on ThinPrep 2000® (TP) (Cytyc Corporation, Marlborough, Massachusetts, U.S.A.) and conventional preparation (CP) specimens from fine needle aspiration cytology (FNAC) material by a semiquantitative scoring system. STUDY DESIGN: In this prospective study a total of 71 consecutive cases were included. In each case, two passes were performed. The first pass was used for conventional preparations, with direct smears made and fixed immediately in 95% alcohol for Papanicolaou stain. For TP preparation a second pass produced material for processing in the ThinPrep 2000® . The TP and CP slides were studied independently by two observers and representative slides of CP and TP compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of monolayer cells, and nuclear and cytoplasmic details by a semiquantitative scoring system. Statistical analysis was performed by Wilcoxon's signed rank test on an SPSS program (Chicago, Illinois, U.S.A.). RESULTS: TP preparations contained adequate diagnostic cells in all cases and were tangibly superior to CP preparations concerning monolayer cells, absence of blood and necrosis, and preservation of nuclear and cytoplasmic detail (statistically significant, Wilcoxon's signed rank test, P

OBJECTIVE: To study the reasons for interpretive errors in false negative diagnosis of breast carcinoma on fine needle aspiration cytology material. STUDY DESIGN: We reviewed only those histologically proved malignant cases where the cytologic material was abnormal and to some extent misinterpreted. RESULTS: There were four lobular carcinomas and one each case of in situ, infiltrating duct, medullary and tubular carcinoma. Smears of lobular carcinomas were hypocellular overall, and the cells showed minimal nuclear pleomorphism. In situ, medullary and tubular carcinoma were associated with fibrocystic changes. The presence of bipolar cells and stromal fragments was misleading in cases of infiltrating duct carcinoma. CONCLUSION: The presence of associated fibrocystic disease may be a misleading factor since it may mask a malignancy. Hypocellularity and relatively nuclear monomorphism were the most common reasons for failure to diagnose malignant breast lesions. Careful attention should be paid to extreme nuclear monomorphism and absence of naked bipolar cells. A cytologically atypical or suspicious diagnosis together with radiologic suspicion should suggest a diagnosis of malignancy.

Background : Development of uterine cervical cancer is preceded by preneoplastic proliferative changes in the cervical epithelium called intra-epithelial neoplasia or dysplasia. The genetic basis of the origin and progression of such preneoplastic lesions is not known. By analysis of carcinomas for loss of constitutional heterozygosity (LOH), we have previously shown a high frequency of allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a candidate tumor suppressor gene located in 5p and associated with the development of this tumor. Purpose : To further understand the role of genetic alterations that affect 5p in cervical carcinogenesis, we evaluated the status of microsatellite polymorphisms at five loci mapped to 5p14-ter in precancerous and cancerous lesions. Methods : Biopsy specimens from two groups of patients were analyzed for genetic alterations affecting 5p. One group comprised 14 cases of precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ (CIS) ; the second group comprised 46 previously untreated patients with invasive carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for genetic losses and instability at five polymorphic microsatellite loci (D5S392, D5S406, D5S208, D5S117, and D5S432) mapped to 5p. Results : LOH was observed in 25 (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Among the loci tested, D5S406 (5p15.1-15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be the site in 5p of the novel candidate tumor suppressor gene. In addition, replication error-type alterations were noted in the 5p14-ter region in six (13%) of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12 instances that showed microsatellite instability. Conclusion : These observations suggest that allelic loss and microsatellite instability in the region of D5S406 may play a role early in the development of cervical carcinoma and identify the site of a candidate tumor suppressor gene. These genetic markers (allelic loss and microsatellite instability) may also define CIS and precancerous lesions at high risk for progression to invasive cancer. Implications : The future molecular cloning of the candidate tumor suppressor gene at 5p15.1-15.2 may provide new insights into the genetic mechanisms of cervical carcinogenesis. Analysis and clinical follow-up of a large cohort of prospectively ascertained cases of precancerous lesions would help to validate the usefulness of these markers. [J Natl Cancer Inst 87 :742-745, 1995]

Ninety-six colposcopical ly directed biopsies from squamous epithelial carcinoma of the uterine cervix and 22 age-matched normal control biopsy specimens were examined by both Southern blot hybridization and polymerase chain reaction (PCR) for the presence of different human papillomavirus (HPV) DNA types. Cancer of the uterine cervix, which is the most common malignant disease in Indian women, showed a high frequency (98%) of HPV as compared to those reported from other parts of the world. HPV type 16 was found to be the dominant (64%) type while the frequency of HPV type 18 was verylow (3%). On individual typing of HPV, no biopsy was found to contain any other known HPV types under stringent conditions of hybridization except a single case of HPV type 11. Only one case of double infection with HPV types 16 and 18 was recorded. Under low stringency conditions of hybridization with a mixed probe of HPV types 16 and 18, 29 additional biopsies were found to be positive. Southern blot hybridization alone detected HPV DNA in 92% of the cases but none in the controls. By PCR, six (6.25%) more cases and four (18.18%) healthy women were found to be positive for HPVs. Analysis of the physical state of HPV 16 indicated integration in about 70% of carcinoma cases while 30% of them were in episomal form. The findings suggest that infection with HPV is an important etiologic factor for the development of cervical cancer, that a number of such tumours may arise without HPV infection, and that integration of the viral DNA into host genome is not always essential for malignant progression. Furthermore, the use of PCR provides an effective complementation of Southern blot hybridization for meaningful epidemiological studies of HPV infection.

OBJECTIVE--To assess the efficacy of visual screening for cervical cancer in the maternal and child health setting. DESIGN--Clinical and cytological screening. SETTING--Maternal and child health centres, Delhi. SUBJECTS--44,970 women attending the centres from May 1988 to March 1991. RESULTS--238 cancers in early stages (0-IIa) were detected cytologically and proved through biopsy. Prevalence of cancer in women defined as high risk through examination by speculum was 29/1000 as compared to 1.53/1000 among women with a normal looking cervix. Though only 11.4% women belonged to the high risk category, 63% had early stage cancer. If all women with bleeding symptoms were included in the high risk category, the yield of cancer would be 71.4% (170/238) by referring only 15.6% of women attending maternal and child health centres for further evaluation through cytology or colposcopy. CONCLUSION--Though visual screening is a suboptimal strategy in comparison to the cytological screening, it may be useful where there is a heavy load of prevalent cancer and where cytological screening may not be available for years to come.

To evaluate the supportive role of image cytometry and DNA ploidy pattern in the diagnosis of thyroid tumors, a preliminary study was performed on fine needle aspirates of 30 cases. Of these, 10 cases each were of colloid goiter, follicular neoplasm, and papillary carcinoma. The nuclear area and DNA value of 50 cells in each case were measured. The mean nuclear area in colloid goiter (69.50 + 12.62 sq.microns) was significantly lower than the mean nuclear area in a follicular neoplasm (88.71 + 15.51 sq.microns) (P less than 0.05). Similar differences between the mean nuclear area in colloid goiter and papillary carcinoma (124.0 + 12.27 sq microns) was also highly significant (P less than 0.001). The results obtained by image cytometry were compared with estimated DNA ploidy pattern of follicular cells from the same cases. All colloid goiter had mean nuclear area below 100 sq.microns with diploid DNA value. However, papillary carcinoma showed aneuploid DNA pattern in eight cases (80.0%), but mean nuclear area was above 100 sq.microns. A diagnostically useful finding obtained in two of the 10 cases of follicular neoplasm was the association of aneuploid DNA pattern with mean nuclear area of the follicular cells above 100 sq.microns indicating a high probability of carcinoma and thus demanding an urgent open biopsy. These cases were readily distinguished from other cases of the same category showing diploid DNA pattern and mean nuclear area of follicular cells below 100 sq.microns.

Worldwide, the subject of human reproduction is shifting from a mainly “demographic issue” to a broader women’s health and development issue that is viewed as a key determinant of both individual well-being and societal prosperity. A general consensus now exists that reproductive health not only should include the ability to regulate fertility, but must also ensure optimal conditions for safely fulfilling the biological role of reproduction, namely, bearing and raising healthy children. Sound reproductive health policy and programs also must help both women and men to handle their sexuality with responsibility and dignity. These programs would enable women and men to cope with problems such as reproductive ill health—by preventing and treating sexually transmitted diseases (STDs) and other reproductive tract infections (RTIs)—as well as providing infertility and safe abortion services. Though many diseases place a heavy burden of morbidity and mortality on both men and women in developing countries, women are more often seriously affected because of synergistic effects of infection, malnutrition, and reproduction.

Nuclear DNA content was determined by microphotometry in 27 cases of moderate dysplasia of the uterine cervix. All these cases were followed from one to ten years to study the biological behavior of moderate dysplasia in relation to cervical carcinogenesis. Ten of them showed progression to carcinoma in situ during a period of one to six years (median 34.8 months) and 17 cases showed regression to inflammation and normalcy during a period of one to ten years (median 44.2 months). DNA analysis was performed both on initial cervical smear and on representative smears collected during follow-up. Amongst ten cases which progressed to malignancy, nine had aneuploid DNA pattern and one had polyploid DNA pattern throughout the follow-up period. Amongst 17 cases which regressed to inflammation, 11 had euploid and six polyploid DNA pattern. The observation that moderate dysplasia with aneuploid DNA value often develops into carcinoma in situ in contrast to dysplasia with euploid or polyploid DNA value strengthens the conception that DNA aneuploidy may be considered as 'high risk indicator' for cervical precancerous lesions.

Since cytology-based screening programmes for cervical cancer cannot be provided on a large scale in developing countries, an alternative approach is needed. To find out whether visual inspection of the cervix is an adequate alternative, women with cytological evidence of dysplasia were followed up cytologically and colposcopically until cancer was detected, and the gross appearance of the cervix was recorded at each stage. Although only 40-50% of cancers were accompanied by abnormal-looking cervices, whereas 71% were detectable on cytology and 87% on colposcopy, visual inspection may be useful in areas where cytological screening programmes are not available.

The number of silver-staining NORs (rDNA)/cell and their pattern of distribution were studied in phytohaemagglutinin-stimulated blood lymphocyte chromosomes of different age group individuals starting from newborns to old age (0–75 years) in order to investigate if the number of Ag-NORs or rDNA genes varies during development in humans. The results indicate presence of a relatively high modal number of NORs in newborns and infants (9.00 and 8.00/cell, respectively) and a significantly reduced number in old individuals (6.00/cell) as compared to that of normal adults (7.00/cell). These data are complimentary as well as comparable to the previous findings of Denton et al. (Mech. Ageing Dev. 15 (1981) (1–7). It is suggested that at young age due to an obvious enhanced growth and differentiation more gene sites may be transcriptionally active showing higher number of silver-stained NORs but as the development proceeds and the age advances many of these may be gradually repressed or inactivated.

The most common malignant tumor among Indian women is carcinoma of the uterine cervix. Environmental factors in different parts of the country such as socioeconomic conditions sexual experience age at marriage fertility and penile hygiene affect the varying frequency of its occurrence. A study of vaginal smears of 39587 Indian women disclosed 693 cases of cervical cancer. Of these only 4 cases were seen in Christian women. The cancer rate was significantly higher among Hindu and Muslim women between 45 and 54 years of age. The average age at marriage of women with cervical cancer was 13.6 years as compared with 15.6 years for the control group. In addition the cancer rate was significantly high in Hindu and Muslims who had more than 4 full term deliveries. The majority of patients with cervical cancer belonged to the low socioeconomic group. The findings suggest that the high incidence of cervical cancer in Indian women is associated with poverty early sexual experience early pregnancy and multiparity.

There is no invasive cancer which at one stage was not cancer-in-situ. The cervical cancer if detected at its pre-invasive stage is amenable to treatment with 100% survival rate. The knowledge that cancer is preventable if detected in its precancerous stage or is curable if detected in its early stage strongly supports the need for routine cytological examination of all young females from time to time for detection of cervical neoplastic lesion in its early stage and a follow-up of all the dysplastic lesions of cervix. Present study comprises of an examination of vaginal smears of 39,587 women aged 14 to 80 years. Malignancy of female genital tract was observed in 693 cases. On cytological and histological examination the cancer of the cervix was diagnosed in 64 clinically unsuspected cases giving a pick up rate of 1.62/1000. In each of these cases the initial clinical impression of the cervix was other than carcinoma, the first indication of malignancy being the result of cytological examination. Cervical dysplasia was detected in 927 cases. A follow-up study of progression or regression of dysplastic changes was done.

Nucleolar organizer regions (Ag-NORs) were studied in patients with cervical precancerous and cancerous lesions along with controls. The data revealed a statistically significant decrease of Ag-NORs in cancer patients, as well as in women with severe precancerous lesions as compared with controls. A similar decrease in the amount of Ag-staining was also observed in both cancer and severe dysplasia cases. The study suggests a possible relationship of Ag-NOR activity to malignancy.

Genital warts are a fairly common sexually transmitted disease and often affect young, illiterate subjects of poor socioeconomic status in India. The mean incubation period was 2.4 months, and the duration varied from 10 days to 4 years. Hyperplastic sessile, verruca vulgaris-like, and flat variants of warts were seen in that sequence, with distinct clinical features. The epidermal and the dermal changes were largely identical; however, the flat type in the epidermal changes were inconspicuous. Koilocytosis was a pathogno-monic feature in 28, whereas human papilloma virus (HPV) antigens were detected through peroxidase-antiperoxidase technique in 18 patients.

C-band heteromorphisms of chromosomes 1, 9 and 16 were studied in 62 patients with cervical cancer, 100 women with various grades of precancerous lesions and 47 normal women as controls. The data showed an increased frequency of heteromorphisms of chromosome 1 in patients with cancer (48.39%) and severe dysplasias (40%) as compared to controls (29.8%) and lower grades of dysplastic lesions, i.e. mild and moderate (28.8%). The increase in the incidence of chromosome 1 heteromorphisms in cancer was found to be statistically significant (p less than 0.05) compared to controls. The present study indicates that C-band heteromorphisms may play some role in the development of malignancy of the uterine cervix.

Chromosomal aberrations were studied in metaphases from peripheral blood cultures of 52 women with cancer of the cervix uteri, 89 cases of various grades of cervical precancerous lesions, and 47 age-matched normal (control) women. The frequency of metaphases with chromosome and chromatid aberrations was 17.24% in cancer patients, 10.41% in those with precancerous lesions, and 6.39% in control women. There was a significant (p less than 0.001) increase in the frequency of chromosome aberrations in patients with cervical precancerous and cancerous lesions, compared with controls. After the exclusion of the treated cases, cancer patients also revealed a highly significant (p less than 0.001) increase in the frequency of chromosome aberrations, compared with controls. The results of the present study indicate the existence of chromosomal instability in the majority of cervical cancer patients and in some cases of precancerous lesions. The increased frequency of spontaneous chromosome aberrations in patients with precancerous lesions may be of importance for the understanding of their biological behavior.

Double-minute chromosomes (DMs) were observed in repeated samples in the leukocytes of a patient with a previous history of cervical carcinoma. The most interesting cytogenetic finding was the coexistence of DMs and a dicentric chromosome along with chromosome- and chromatid-type breaks and gaps. This observation suggests that DMs might originate through the breakage of existing chromosomes. The presence of DMs in leukocytes may also indicate the possibility that certain common agents cause DMs in tumor cells as well as in normal cells.

A cytogenetical analysis of chromosomal aberrations, sister chromatid exchanges (SCEs), C-band heteromorphisms and nucleolar organizer regions was done in lymphocytes of 30 patients with precancerous lesions of the uterine cervix progressed to carcinoma and of 30 patients with nonprogressed lesions in a period of 60 months follow-up, in order to identify if any differences existed between low-risk and high-risk dysplasias. Increased frequency of chromosomal breaks, SCEs and C-band heteromorphisms of chromosome 1 and decreased activity of ribosomal genes was observed in patients with dysplasias progressed to carcinoma compared to that of nonprogressed precancerous lesions. The present study thus suggests an intimate relationship between the constitutional chromosomal phenotypes and development of cancer, and these may serve as useful biological markers in defining dysplasias at high risk to progress to cancer.

Heparinised cord blood from newborns and peripheral venous blood from three other age groups of individuals (1-75 years) have been cultured in vitro to obtain baseline frequencies of SCE and to see if the frequency of baseline SCE in vitro varies as a function of aging in vivo. The results demonstrate an age-dependent variation in the frequency of SCEs. Although the SCE frequency was lowest (5.10/cell) in 1-5-year-old infants, a significantly higher (P less than 0.001) frequency (8.97/cell) was observed in the cord blood of newborns. In old age, the level of SCE also increased. The plausible reason(s) for such observations is discussed.

Cancer of the uterine cervix is the most common malignancy among Indian women. Evidence has shown that cervical cancer is preceded by dysplastic, or precancerous, lesions. HSV-II has been associated with this process of cervical carcinogenesis. We collected 167 cervical smears that had been diagnosed as normal, dysplastic, or carcinoma-in-situ and found a significantly high positivity of HSV-II antigen in women with cervical dysplasia (38.8%) and carcinoma-in-situ (33.3%) versus women with normal cytology (17.02%). Latent HSV-II infection of cervical epithelium may be considered of prognostic value to identify a population at high risk for cervical cancer.

Carcinoma of the cervix is known to have a multifactorial etiology and several factors are implicated in increasing the risk of eventual development of cervical malignancy in a woman. This communication attemps to highlight the small family norms in the prevention of uterine cervical cancer. Data on 117,411 cytologically screened women were considered in which 215 women were found to have cervical cancer. Age adjusted rates of malignancy per 100,000 women in three parity groups (0-2, 3-4 and 5+) were 91.1, 174.4 and 393.1 respectively. An increasing trend of malignancy was noticed with increasing parity in women who had their consummation of marriage before 18 years as well as after 18 years. It may be concluded that the small family norm (only two children) being advocated as a part of a national family welfare program would be another primary prevention measure against uterine cervical cancer.

The frequency of sister chromatid exchange (SCE) was investigated in 13 women with cervical cancer together with 11 control women. The SCE frequencies were found to be 10.05 +/- 2.35 and 6.95 +/- 1.53 in cancer cases and controls, respectively. The SCE values of cancer cases deviate significantly from that of controls. The SCE in chromosome groups E, F, and G was found to be more in comparison to controls (P less than 0.001). This preliminary study indicates the possibility of using SCE as a preclinical marker.