HISTOPATHOLOGICAL CATALOGUE FOR THE PRE-MALIGNANT AND MALIGNANT LESIONS OF UTERINE CERVIX AT A TERTIARY CARE CENTRE OF MAHARASHTRA

cancer mortality in India. The transformation zone of the cervix is vulnerable to HPV. A preneoplastic cervical intraepithelial neoplasia can regress, persist or progress towards invasive carcinoma. Aims: To study the prevalence and histopathological spectrum of premalignant and malignant lesions of uterine cervix. Methods: This was a retrospective cross-sectional study, carried out at Tertiary Care Hospital, in Department of Pathology, over a period of one-year. Results: Total 14 cases (8%) of total hysterectomy and 156 cases (92%) of cervical biopsy were included, which included31 cases (18%) premalignant lesions (CIN-I, II, III, CIS) and 139 cases (82%) malignant. SCC was found in 73% cases and adenocarcinoma in 8.3%. Limitations: Follow-up was not possible. Conclusions: Awareness programs and educational sessions might help to reduce the burden of carcinoma cervix in India. carcinoma was 48.5 years.Kaveri SB et al, Bagde S et al, Metha A et al and Bojini K R et al 6,7,8,9 found maximum number of cases of unhealthy cervix in the age group of 31-40 years. These studies substantiate that the disease process starts approximately 10-12 years before the development of invasive carcinoma and holds true for all regions of India.


ISSN: 2320-5407
Int. J. Adv. Res. 8(09), 714-723 715 25%, and adenosquamous carcinomas 3-5%. Adenocarcinomas have been rising in incidence since the 1970s; especially in women younger than 35 years of age, may be attributed by an increasing prevalence of high risk Human Papilloma Virus (HPV) infection. 2 The transformation zone of the cervix, specifically that associated with squamo-columnar junction, is vulnerable to HPV. Also, age at first intercourse has important role to play. A preneoplastic cervical intraepithelial neoplasia can regress, persist or progress towards invasive carcinoma. Thus, the goal of cervical cancer prevention program is to detect and treat all committed cancer precursors before invasion develops. 4 Carcinoma cervix is more common in the low socioeconomic class, with lack of awareness of risk factors and presenting at an advanced stage, 4 who fail to carry out regular health check-up due to financial insufficiency. 3 There is a need for National cervical screening and education programs for women especially in rural areas. Studies show that histologic assessment is strongly associated with decreased risk of invasive carcinoma compared to repeated cytology in women with low grade squamous abnormalities. 4 Some tumors are clinically in apparent and are diagnosed for the first time during PAP/cervical biopsy/ hysterectomy done for benign pathology.Early detection in preclinical stage ensures 100% survival rate. The ultimate aim of various modalities of diagnosis and treatment is to prevent the development of invasive cervical cancer. 3 Thus, the present study was carried out with the aim to study the prevalence and histopathological spectrum of premalignant and malignant lesions of uterine cervix at a Tertiary Referral Centre with maximum patients coming from a low socioeconomic stratum.

Materials and Methods:-
The present study was a retrospective cross-sectional study, carried out at Tertiary Care Referral Hospital. This study was carried in Department of Pathology, over a period of one-year from June 2018 to June 2019. Among 2862 histopathological specimens received, total 462 were found to be total hysterectomy (abdominal/ vaginal) specimens and 285 were cervical biopsies. All these specimens along with their operative findings were received from Department of Obstetrics and Gynaecology. Clinical history with age, presenting signs & symptoms, possible serum marker assays, radiological and operative findings were studied.

Inclusion criteria:
All histologically proven premalignant and primary malignant lesions of the uterine cervix Exclusion criteria: Non neoplastic lesions, benign tumours, secondary tumours involving the cervix, inadequate and autolyzed samples Gross examination of 10% formalin fixed specimen was done and processed. 1) Cervical biopsies were embedded in toto. Serial sections were also taken wherever needed. 2) In cervix, with no obvious gross abnormality, sections were taken from anterior and posterior lip including the squamo-columnar junction. 3) In hysterectomy specimens with a prior history of cervical Pap smear positive for Low squamous intraepithelial lesion (LSIL) or High Squamous intraepithelial lesion (HSIL), multiple sections were taken along the endocervical canal, in such a way that epithelium including squamo-columnar junction is present in each section.
Lesions of the cervix were classified into premalignant and malignant, which were further typed using the World Health Organization histological classification for tumours of the uterine cervix [8]. The histopathologic features analyzed were: Pattern of infiltration, nuclear pleomorphism, character of tumour stromal border or mode and stage of invasion, degree of stromal inflammatory cell infiltrate, presence or absence of lympho-vascular invasion, mitotic index and degree of tumour differentiation. 4,5 Results:-Out of the total of 462 total hysterectomy specimen, 14 cases (8%) were included. Out of 285 cervical biopsies, 156 cases (92%) were included in the present study. (Fig 1) 716 Figure 1:-Distribution of cases according to the type of histopathological specimen received (n=170).
In the present study, youngest female of 28-years was diagnosed to have Adenocarcinoma of cervix and the oldest of 83-years to have Squamous Cell Carcinoma (SCC) -spindle cell variant. Most common age group to be affected by premalignant and malignant cervical lesions was found to be 51-60 years, followed by 41-50 years. (Fig 2) Two cases with Cervical Intraepithelial Neoplasm (CIN) -I were found to be in the age group of 21-30 years. While all cases with CIN-II, CIN-III and Carcinoma-in-situ (CIS), fall in 31-40 years of age. Most of the cases diagnosed as SCC were in the age group of 51-60 years and that diagnosed as adenocarcinoma were in 41-50 years of age group. Most of the females in the present study were multiparous presenting with either blood mixed white discharge or bleeding per vagina (PV). Per speculum (PS) examination of the malignancy suspected females revealed friable growth, which bleeded on touch.
Present study found 31 cases (18%) as pre-malignant lesions (CIN-I, II, III, CIS) and 139 cases (82%) as malignant.  Most common pre-malignant lesion was CIN-III (7.6%), followed by CIN-I (4.7%). Least common was CIN-II (2.2%). While CIS was found to be 3.5% cases. (Table 1) (Fig 4) SCC was found to be most common lesion (73%), followed by adenocarcinoma (8.3%). In SCC, keratinizing type outnumbered the series (43.1%), with least of basaloid type (0.6%). (Fig 5) Whereas, conventional type of adenocarcinoma (3.5%) outnumbered, followed by papillary serous type (1.7%). (Fig  6) A very rare case of melanoma of cervix was found in a 70-years female, presenting PV-bleed, showing blackish mass blocking the cervical canal on PS-examination. (Table 2)     Cancer that develops in the ectocervix is usually SCC, and around 80-90% of cervical cancer cases (more than 90% in India) are of this type. Cancer that develops in the endocervix is usually an adenocarcinoma. In addition, small percentages of cervical cancer cases are mixed versions of the above two and are called adenosquamous carcinomas or mixed carcinomas. 2 Present study found SCC of cervix to be the most common (73%), followed by adenocarcinoma (8.3%). This was comparable to study done by Jain In recent years it has been suggested that there has been a relative and absolute increase in the incidence of adenocarcinoma of the uterine cervix as shown in studies of Chen J et al., which was done on a large population based database. 13 In present study, SCC was commonly found in 51-60 years of age and adenocarcinoma in 41-50 years. .11% of small cell SCC and 2.35% of verrucous carcinoma. Sarcomatoid carcinoma is a very rare pathological entity of the female genital tract and even more rare in the cervix. It has been described more frequently in the aero-digestive tracts and skin. 19 Brown et al reported the largest series of 9 cases of sarcomatoid carcinomas of the cervix with a median disease-free interval of 4.9 months. 20 Uterine cervix is a rare site for Basaloid variant of SCC, usually affecting patients in their 6th and 7th decade of life. Though there are occasional reports mentioning younger patients. 21 Only one case (0.6%) of basaloid SCC was noted in the present study.
Adenosquamous carcinomas previously considered as a subtype of cervical adenocarcinomas is now considered a special and rare histological type accounting for 5-10% of cervical carcinoma and has a poor outcome. In study done by Gupta M 4 , one case with morphological features of adenosquamous carcinoma was reported. Present study found adenosquamous type of adenocarcinoma in 1.18% cases. (Fig 6O) The significance of an endophytic or exophytic growth pattern, in cases of adenocarcinoma has been debated. Most lesions of adenocarcinoma appearing as endophytic growth may be the manifestation of site of origin of adenocarcinoma within glandular epithelium of endocervix. Whereas, appearance of an exophytic lesions is a result of extension from endocervical glands or its development in a congenital ectropion. 4 Variants of adenocarcinoma are -1) Conventional, 2) Endometrioid, 3) Papillary serous, 4) Adenoma Malignum, 5) Villoglandular, 6) Adenosquamous, 7) Glassy cell carcinoma, 8) Adenoid cystic carcinoma and 9) Clear cell carcinoma. In present study, conventional type of adenocarcinoma was found to be most common (3.53%), followed by papillary serous type (1.76%). While adenoma malignum, villoglandular and adenoid cystic type of adenocarcinoma was found to be in 0.6% each. (Fig 6)

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A very rare case of melanoma of uterine cervix was seen in present study (0.6%). (Fig 5G)Malignant melanoma accounts for about 0.03% of all newly diagnosed cancers and malignant melanomas of the female genitalia occur very rarely -accounting for approximately 2% of all melanomas. Primary malignant melanoma of the uterine cervix has no early symptoms and the diagnosis is usually delayed; therefore, prognosis is very poor. 23 Histopathologically, majority of tumours showed few to moderate number of mitotic figures, lymphovascular invasion, lymphoplasmacytic stromal response was moderate to severe. Similar histological findings were observed by Gauthier P et al 24 and van Nagell JR et al. 25 The objective of determining tumour grade (degree of differentiation) is to estimate biologic behaviour and aid inpatient management. Extension of SCC into endometrium and/or myometrium, in hysterectomy specimens, focuses attention on the need for a more complete biopsy procedure and pretreatment workup prior to initiation of therapy. 4 Bodal VK et al found maximum number of patients were in the fourth decade of life followed by fifth decade. 26 Rathoda GB et al 27 found most patients were in the age group of 41-50 years (42.4%) followed by age group 51-60 years.In present study, maximum patients were seen in the age group of 51-60 years (38.8%), followed by 41-50 years (21.17%).

Limitation:
The limitation of the present study was that the follow-up was not possible with malignancy cases as they were referred to higher Centre for further management. Also, in cases with CIN, diganosed on cervical biopsy, we were not able to observe its progression or regression.

Conclusion:-
Cervical cancer continues to be the most common cancer of females in developing countries like India. One of the most significant advances in the management of cervical neoplasms has been the realization that CIN behave as progressive stages to the development of invasive cancer. Histopathological examination is considered gold standard for diagnosis of CIN and cervical carcinoma. Light microscopy is sufficient for the diagnosis of almost all cases, whichminimizes the need for Histochemical stains and Immunohistochemistry in only a few histologic types, particularly in poorly differentiated carcinoma and neuroendocrine tumours. Histologic evaluation of CIN and cervical carcinoma should be attempted at an early stage of disease (since CIN starts at 30-40 years of age) to provide better prognosis, treatment and protection against invasive cervical carcinoma. With recent advancements in molecular techniques more studies comparing different histological features and biomarkers need to be conducted to ensure development of targeted therapy and prevention of invasive carcinomas.
All females with unhealthy cervix should undergo Pap smear or a cervical punch biopsy. Carcinoma cervix is ideal malignancy for screening as it has a long latent period and can be detected at premalignant condition and also prevented from progression to invasive disease. Thus, advantages of screening for carcinoma cervix far outway for cost involved.
Awareness programs and educational sessions might help to reduce the burden of carcinoma cervix in India.