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Histopathological Pattern of Endometrial Hyperplasia in Peri- and Postmenopausal Women


Histopathological Pattern of Endometrial Hyperplasia in Peri- and Postmenopausal Women

*Fardousi F,1 Sultana SS,2 Kaizer N,3 Dewan RK,4 Jinnah MS,5 Jeba R,6 Hoque MN,7 Hussain M8

Abstract

Endometrial hyperplasia is one of the major gynaecological problem in peri- and post-menopausal women worldwide. It deserves special attention because of its relationship with endometrial carcinoma. The histopathological pattern of endometrial hyperplasia in peri- and post-menopausal women and their relationship with clinicopathological features are imperative to reach a diagnosis as well as early management. To find out the histopathological patterns of endometrial hyperplasia in peri- and post-menopausal women this descriptive cross-sectional study was carried out at the Department of Pathology, Dhaka Medical College, Dhaka during the period from January 2013 to December 2014. A total of seventy histopathologically diagnosed cases of endometrial hyperplasia were included in this study according to inclusion and exclusion criteria. Among the 70 cases, endometrial curettage biopsy specimens were 45 and hysterectomy specimens were 25. Routine Haematoxylin & Eosin staining was done on all cases. Out of all endometrial hyperplasia cases, 53 cases were simple endometrial hyperplasia without atypia, 8 cases were simple endometrial hyperplasia with atypia, 6 cases were complex endometrial hyperplasia without atypia and 3 cases were complex endometrial hyperplasia with atypia. Majority of the patients 35 (50%) were between 41-50 years of age. The study revealed that most common histopathological pattern of endometrial hyperplasia was simple endometrial hyperplasia without atypia, followed by simple endometrial hyperplasia with atypia. The importance of knowledge about the histological pattern of endometrium in abnormal uterine bleeding in different age group is useful in managing the cases with accuracy.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):30-40]

 Key words: Endometrial hyperplasia, gynecological problem, peri- and postmenopausal women, histopathological pattern.

  1. *Dr. Farzana Fardousi, Lecturer, Department of Cytopathology, National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka. farzanafardousi@yahoo.com
  2. SK Salowa Sultana, Assistant Professor, Department of Pathology, Ad Din Women’s Medical College.Dhaka
  3. Nahid Kaizer, Associate Professor (CC), Department of Pathology, Shahabuddin Medical College. Dhaka
  4. Professor Dr. Rezaul Karim Dewan, Head of the Department of Pathology, Dhaka Medical College.
  5. Mohammed Shahed Ali Jinnah, Associate Professor, Department of Pathology, Dhaka Medical College.
  6. Ruksana Jeba, Associate Professor Department of Pathology, Dhaka Medical College.
  7. Md. Nazmul Hoque, Ex Associate Professor, Department of Pathology, Dhaka Medical College
  8. Professor Dr. Maleeha Hussain , Ex Head of the Department of Pathology, Dhaka Medical College.

*For correspondence

Introduction

Endometrial hyperplasia is defined as an increased proliferation of the endometrial glands relative to the stroma, resulting in an increased gland-to-stroma ratio when compared with normal proliferative endometrium. Endometrial hyperplasia deserves special attention because of its relationship with endometrial carcinoma in peri and postmenopausal women.1 Worldwide, endometrial cancer is the most common invasive cancer of female genital tract.

In 50% cases of endometrial adenocarcinoma, endometrial hyperplasia particularly atypical hyperplasia is found as a premalignant lesion.2 Endometrial hyperplasia usually develops in the presence of continuous estrogen stimulation unopposed by progesterone. In the years before menopause, women may have numerous cycles without ovulation (anovulatory) during which there is continuous unopposed estrogen activity. Similarly, hormone replacement therapy consisting of estrogen without progesterone may lead to endometrial hyperplasia.3 The endometrium becomes atrophic after menopause as a result of ovarian failure. The postmenopausal endometrium which despite being atrophic, retain a weak proliferative pattern for many years probably as a response to continuous low level of estrogenic stimulation. These are at a higher risk of progression to endometrial hyperplasia and subsequently to endometrial malignancy.3 Many classifications of endometrial hyperplasia have been proposed over the years. The one that is currently preferred and which has been recognized by the World Health Organization (WHO) was originally proposed.4 It takes into account both the architectural and cytologic features, for reasons of dividing the hyperplasias into simple and complex based on architecture and subdividing each into typical and atypical on the basis of their cytological pattern.5 The type I endometrial cancers which is endometrioid variant is associated with unopposed estrogen exposure and is often preceded by atypical endometrial hyperplasia. However, type II endometrial cancers where a non-endometrioid histology (usually papillary, serous or clear cell) has an aggressive clinical course, is not preceded by any type of endometrial hyperplasia.6 According to WHO, endometrial hyperplasia is divided into four major categories: Simple hyperplasia without atypia, Simple hyperplasia with atypia, Complex hyperplasia without atypia and Complex hyperplasia with atypia. The confirmed diagnosis of endometrial hyperplasia can be made by histopathological examination.7 Endometrial hyperplasia is associated with prolonged estrogen stimulation of the endometrium, which can be due to anovulation, increased estrogen production from endogenous sources or exogenous estrogen. The factors associated with endometrial hyperplasia include obesity, menopause, polycystic ovarian diseases, functioning granulosa cell tumors of the ovary, excessive cortical function and prolonged administration of estrogenic substances.1 The primary presenting symptom of endometrial hyperplasia is abnormal uterine bleeding, which typically prompts an endometrial biopsy to rule out carcinoma.8 Approximately, 70% of women with abnormal uterine bleeding are diagnosed with benign findings and 15% are diagnosed with carcinoma. The remaining 15% receive a diagnosis of endometrial hyperplasia, which includes a broad range of lesions, from mild, reversible proliferations to the immediate precursors of carcinoma. Abnormal uterine bleeding is the chief complaints of endometrial hyperplasia and can be categorized into dysfunctional uterine bleeding or postmenopausal bleeding. Long reproductive life has risk for development of endometrial hyperplasia. Different studies have shown that, women who have achieved early menarche or late menopause have more risk for development of endometrial hyperplasia and endometrial carcinoma, as estrogen exposure especially unopposed by progesterone is a known risk factor for the development of endometrial carcinoma. Parity causes estrogen-hormonal environment throughout the fertile years of a woman, which may increase risk for the development of endometrial carcinoma.9 Obesity is a known risk factor for endometrial hyperplasia and this excess risk is associated with the endocrine and inflammatory effects of adipose tissue. Adipocytes express aromatase that converts ovarian androgens into estrogens, which induce endometrial proliferation.10 It was observed in different studies that, endometrial hyperplasia was found in diabetic and hypertensive patient, but whether this association is statistically significant or not or whether it carries a risk of endometrial carcinoma for diabetic and hypertensive women need to be ascertained with further studies in a larger series of population. It was observed in many studies that endometrial hyperplasia is associated with family history of endometrial cancer. Because a common genetic alteration found in a significant number of endometrial hyperplasias and related endometrial carcinomas i.e. inactivation of the PTEN tumour suppressor gene.11 The study was aimed to find out the histopathological patterns of endometrial hyperplasia in peri- and post-menopausal women.

Methods

Place and period of study

This is a descriptive cross-sectional study which was carried out at the Department of Pathology, Dhaka Medical College, Dhaka, during the period of January 2013 to December 2014.

Sample Size

For this study, 110 peri- and postmenopausal women with dysfunctional uterine bleeding or postmenopausal bleeding who underwent D&C or hysterectomy were screened. A total of seventy histopathologically diagnosed cases of endometrial hyperplasia who met the enrollment criteria (inclusion & exclusion criteria) were included in this study. Among 70 cases, endometrial curettage biopsy specimens were 45 and hysterectomy specimens were 25. Routine Haematoxylin & Eosin staining was done on all cases.

Collection of Sample

Ethical clearance was taken for this study from institutional ethical committee of Dhaka Medical College, Dhaka. Each patient was interviewed before collection of the specimen and relevant information was recorded in a prescribed clinical proforma. Detail history with particular attention to age, clinical features, age at menarche, parity, obesity, history of contraceptives, history of hormone replacement therapy, history of diabetes, history of hypertension, history of estrogen producing ovarian tumor, age at menopause were taken.

 Histopathological Examination

All specimens obtained either by endometrial curettage biopsy or hysterectomy were immersed in 10% formalin. The specimens were examined in the department of pathology, Dhaka Medical College with a particular emphasis on number, size, shape, color and consistency. This part was done by experienced pathologist in the department of Pathology of Dhaka Medical College. Tissue processing and staining: Routine tissue processing and Haematoxylin & Eosin staining were done at the Department of Pathology, Dhaka Medical College.

Microscopic Analysis

Following histopathological diagnoses were made according to WHO classification of endometrial hyperplasia: Simple endometrial hyperplasia without atypia, Simple endometrial hyperplasia with atypia, Complex endometrial hyperplasia without atypia, Complex endometrial hyperplasia with atypia.5

Statistical Analysis

Statistical analyses of the results were obtained by using window based computer software devised with Statistical Packages for Social Sciences (SPSS-16). Percentages were calculated to find out the proportion of the findings. The results were presented in Tables and Figures.

Results

Out of 70 histopathologically diagnosed endometrial hyperplasia cases, 53 cases were simple endometrial hyperplasia without atypia, 8 cases were simple endometrial hyperplasia with atypia, 6 cases were complex endometrial hyperplasia without atypia and 3 cases were complex endometrial hyperplasia with atypia. Majority of the patients 35(50%) were between 41-50 years of age (Table I).

Table I: Distribution of the study patients by Age (n=70)

 

Age (Years) SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
35-40 12 1 4 1 18 25.7
41-50 30 5 0 0 35 50.0
51-60 11 2 1 2 16 22.9
61-70 0 0 0 0 0 0.0
>70 0 0 1 0 1 1.4
Total 53 8 6 3 70 100

 

(SEH without atypia- Simple endometrial hyperplasia without atypia, SEH with atypia- Simple endometrial hyperplasia with atypia, CEH without atypia – Complex endometrial hyperplasia without atypia and CEH with atypia- Complex endometrial hyperplasia with atypia)

Table II: Distribution of the study patients by menstrual history (n=70)

 

Menstrual history SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
Irregular menstrual bleeding 42 8 4 1 55 78.6
Post-menopausal bleeding 11 0 2 2 15 21.4

Majority of the patients (56 cases) achieved their menarche at 12-13 years of age in simple endometrial hyperplasia without atypia and no patient achieved early menarche (before 10 years) (Table III)

Table III: Distribution of the study patients by age of menarche (n=70)

 

Age of menarche (years) SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
12-13 47 3 4 2 56 80.0
14-15 6 5 2 1 14 20.0
Mean±SD 13.7±0.7 13.8±1.3 13.3±1.0 12.7±0.6 13.6 ±0.9
Range (Min-max) 12-15 12-15 12-15 12-13 12-15

 

Out of 70 cases, 45(57.14%) were multipara. Among 45 cases, 36(51.4%) cases had 3 children, 6(8.6%) cases had 4 children and 3(4.3%) cases had 5 children (Table V).

By Basal Metabolic Index, obesity (BMI more than 30) was found in 34(48.6%) cases, among them 27 cases in simple endometrial hyperplasia without atypia, 5 cases in simple endometrial hyperplasia with atypia and 2 cases in complex endometrial hyperplasia with atypia (Table VI).

 

Table IV: Distribution of the study patients by age of menopause (n=70)

 

Age of menopause SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
50 3 0 1 0 4 26.6
51 4 0 0 1 5 33.3
52 4 0 1 1 6 40.0
Mean±SD 51.09±0.8 0±0 51.0±0 51.5±0.7 51.1 ±0.8
Range (Min-max) 50-52 51-51 50-52 51-52 50-52

 

Table V: Distribution of the study patients by parity (n=70)

 

Para SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
2 18 4 2 1 25 35.7
3 29 4 2 1 36 51.4
4 4 0 1 1 6 8.6
5 2 0 1 0 3 4.3
Mean±SD 2.8±0.8 2.5±0.5 3.2±1.2 3.0±1.0 2.8±0.8
Range (Min-max) 2-5 2-3 2-5 2-4 2-5

 

 

Table VI: Distribution of the study patients by obesity by calculating Basal Metabolic Index (BMI) (n=70)

 

Obesity by BMI (kg/m2) SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
Present 27 5 0 2 34 48.6
Absent 26 3 6 1 36 51.4

 

Out of the total study cases, diabetes was found in 11 cases, hypertension was found in 24 cases, and history of associated estrogen producing tumor of ovary was found in 1 case (Table VII).

 

Table VII: Distribution of the study patients by diabetes, hypertension and history of associated estrogen producing tumour of ovary (n=70)

 

Diseases SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
Diabetes 4 5 1 1 11 15.7
Hypertension 20 2 1 1 24 34.3
History of associated estrogen producing tumour of ovary 0 0 0 1 1 1.4

 

History of oral contraceptive pill was found in 15(21.4%) cases and history of hormone replacement therapy was found in 12(17.15%) cases (Table VIII).

 

Table VIII: Distribution of the study patients by history of Oral contraceptive pill (OCP) and history of Hormone replacement therapy (HRT) (n=70)

 

History SEH without atypia

(n=53)

 SEH with atypia

(n=8)

 CEH without atypia

(n=6)

 CEH with atypia

(n=3)

 Total

(n=70)
n %
H/O OCP 7 4 3 1 15 21.4
H/O HRT 10 0 0 2 12 17.15

 

 

 

 

 

 

Figure 1. Photomicrograph showing simple endometrial hyperplasia without atypia (H & E stain, x10)

 

 

 

 

 

Figure 2. Photomicrograph showing simple endometrial hyperplasia with atypia (H & E stain, x40)

 

 

 

 

 

Figure 3. Photomicrograph showing complex endometrial hyperplasia without atypia(H & E stain, x40)

 

 

 

 

 

 

Figure 4. Photomicrograph showing complex endometrial hyperplasia with atypia(H & E stain, x40)

Microscopic pictures of different types of endometrial hyperplasia are shown in figures 1, 2,3 and 4. Pie chart showing the commonest diagnosis in 70 patients was SEH without atypia (75.7%) followed by SEH with atypia (11.4%; Fig-5).

 

 

 

 

Figure 5. Pie chart showing distribution of the patients by diagnosis (n=70)

 

 

 

 

 

Figure 6.  Bar diagram showing distribution of the patients according to mean age with diagnosis (n=70)

Discussion

Endometrial hyperplasia has a significant place in gynecological morbidity in women of reproductive age (10% to 18%).12 It is associated with menstrual irregularities and anaemia in women and poses a high risk for malignant transformation into endometrial cancer.13 Worldwide endometrial cancer is the most common gynecological cancer in peri and postmenopausal women.14,15 The incidence of endometrial adenocarcinoma not only has remained high but in recent years has tended to significantly increase in many countries, including Bangladesh.12,16

 

The diagnosis and classification of endometrial hyperplasia can be made by histopathological examination. The present cross-sectional study was carried out with an aim to observe the histopathological pattern of endometrial hyperplasia in peri and post-menopausal women. In the present study, the commonest diagnosed lesion was simple endometrial hyperplasia without atypia which was 53(75.7%), followed by simple endometrial hyperplasia with atypia 8(11.4%), complex endometrial hyperplasia without atypia 6(8.6%) and then complex endometrial hyperplasia with atypia 3(4.3%).

In this study it was observed that, the mean age was 43.7±7.9 years in simple endometrial hyperplasia without atypia, 44.3±5.9 years in simple endometrial hyperplasia with atypia, 48.5±15.5 years in complex endometrial hyperplasia without atypia and 50.0±13.2 years in complex endometrial hyperplasia with atypia. In our study, the age ranged from 35 to 75 years with a mean age of 45 years. The highest number of cases 35(50%) were in the fourth decade. These findings are almost similar to the studies carried out.17,13 In their study, they also found maximum cases in the fourth decade. However, the present study differed from the study conducted by Trimble et al.2 who reported the mean age as 58 years and the age range between 25 to 89 years. Probably this discrepancy is due to small number of cases in our study. The present study also differed from the study conducted.18 They observed that, the incidence of simple and complex hyperplasia without atypia were highest in women aged 50 to 54 years, whereas the rate of atypical hyperplasia was highest in women aged 60 to 64 years. This variation may be due to high expectancy of life in developed countries.

We observed, 55 cases were in their reproductive age and on menstrual history, all of them had irregular menstrual bleeding. Among 55 cases, majority (42) were diagnosed as simple endometrial hyperplasia without atypical, followed by (8) as simple endometrial hyperplasia with atypia. In this study it was observed that, 15 cases achieved menopause and postmenopausal bleeding. Out of 15 cases, on histopathological examination, 11 were diagnosed as simple endometrial hyperplasia without atypia, 2 as complex endometrial hyperplasia without atypia and 2 as complex endometrial hyperplasia with atypia. This finding is in concordance with that found in the study of Farquhar et al.19 Thus, it can be concluded that, postmenopausal bleeding does not always indicate a risk for development of endometrial carcinoma as simple endometrial hyperplasia without atypia has only 1 to 3% risk for development of endometrial carcinoma.1

In the present study, postmenopausal patients were 15 in number. The mean age at which they achieved menopause was 51.09±0.8 years in simple endometrial hyperplasia without atypia, 51.0±0 years in complex endometrial hyperplasia without atypia and 51.5±0.7 years in complex endometrial hyperplasia with atypia. In this study it was observed that, most patients achieved menopause at the age of 52 years. This result is in concordance with the study done by Jetley et al.20 However, the number of menopausal patient is inadequate to come to any definite comment.

All the patients of this study were parous women. Parity causes estrogen-hormonal environment throughout the fertile years of a woman.9 In the present study it was found that, range of parity varied from 2 to 5 in all types of endometrial hyperplasia. This result is in concordance with the study done by Topcu et al.21,22

They also observed range of parity from 2 to 5 among the patients with endometrial hyperplasia. However, this finding has a pitfall of not having nullipara patient in the present study.

Obesity is a known risk factor for endometrial cancer. This excess risk is associated with the endocrine and inflammatory effects of adipose tissue. Adipocytes express aromatase that converts ovarian androgens into estrogens, which induce endometrial proliferation.10 In the present study, it was observed that by Body Mass Index (BMI), obesity (BMI more than 30) was found in 34 cases (48.6%). Among them, majority (27) cases were simple endometrial hyperplasia without atypia. This result is in concordance with the study done by Epplein et al. 23,21,17 they also found 48.89% cases of endometrial hyperplasia in obese women.

In this study. it was observed that diabetes was found in 11 cases (15.7%). Similar study was done by Bera et al.17 They also found association of diabetes mellitus in 18 cases (15%) of endometrial hyperplasia.

In present study it was observed that, hypertension was found in 24 cases (34.3%). This result is in concordance with the study done by Bera et al.17 They also found 36 cases (35%) of endometrial hyperplasia in hypertensive patients. It is observed that, in the present study and other comparable studies, endometrial hyperplasia is found in diabetic and hypertensive patient, but whether this association is statistically significant or not or whether it carries a risk of endometrial carcinoma for diabetic and hypertensive women need to be ascertained with a large series of study population.

The history of associated estrogen producing tumor of ovary was found in 1 case and it was a case of complex endometrial hyperplasia with atypia. Though this number is very insignificant in our study, Gregory et al.24 have shown in their study that, women with ovarian tumor and polycystic ovarian syndrome (PCOS) have a higher risk of development of estrogen-induced endometrial hyperplasia and cancer.

We observed that history of OCP in 15 cases. Out of 15 cases, 7 cases were simple endometrial hyperplasia without atypia, 4 cases were simple endometrial hyperplasia with atypia, 3 cases were complex endometrial hyperplasia without atypia and 1 case was complex endometrial hyperplasia with atypia. Epplein et al.23 also the found association of OCP in 18 cases of endometrial hyperplasia in the women of reproductive age.

History of hormone replacement therapy (HRT) was found in 12 cases and majority (10) were simple endometrial hyperplasia without atypia. Epplein et al.23 have found similar association with HRT which is composed of estrogen only.

In the present study, no patient gave family history of endometrial hyperplasia or endometrial carcinoma. This may be due to unawareness of the study patients about their family history. Other studies also found no association with the family history of endometrial hyperplasia or endometrial carcinoma, though they were aware about their family history.17, 23

Limitation of the Study

Our study included few numbers of postmenopausal women. It was a cross-sectional study. To evaluate the risk factors for endometrial hyperplasia and the risk of endometrial hyperplasia to progress to endometrial carcinoma, ideally a cohort or follow-up study should be done.

 Conclusion

We found that most of the patients were in the fourth decade and all the patients had chief complaints of either irregular menstrual bleeding or postmenopausal bleeding. On USG, all of them had bulky uterus and all the patients were parous women. We found no significant association with obesity, diabetes mellitus, hypertension, oral contraceptive pill or estrogen producing ovarian tumour but significant association was found with HRT in postmenopausal women. None of the patient had family history of endometrial hyperplasia or endometrial carcinoma.

Recommendations

A large follow–up study is recommended for patients of endometrial hyperplasia selected for conservative treatment with progestogen and GnRH-agonists. Monitoring should be done by observing the Ki-67 expression in these patients. If the Ki-67 expression increases, they should be treated by surgical intervention.

References

  1. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic basis of disease, Professional edition e-book. elsevier health sciences; 2014 Aug 27.
  2. Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke JJ, Alberts D, Curtin J. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia. Cancer, 2006; 106(4):812-9.
  3. Buckley CH. Fox H, Biopsy pathology of the endometrium. 2nd London Arnold, 2002 pp.209-240.
  4. Kurman RJ, Norris HJ. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well differentiated carcinoma. Cancer, 1982; 49(12):2547-59.
  5. Rosai J. Rosai and Ackerman’s surgical pathology e-book. Elsevier Health Sciences; 2011 Jun 20.
  6. Rakha E, Wong SC, Soomro I, Chaudry Z, Sharma A, Deen S, Chan S, Abu J, Nunns D, Williamson K, McGregor A. Clinical outcome of atypical endometrial hyperplasia diagnosed on an endometrial biopsy: institutional experience and review of literature. The American journal of surgical pathology, 2012; 36(11):1683-90.
  7. Pungal A, Balan R, Cotuţiu C. Hormone receptors and markers in endometrial hyperplasia. Immunohistochemical study. Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, 2010; 114(1):180-4.
  8. Lacey JV, Chia VM. Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas, 2009; 63(1):39-44.
  9. Bayo S, Bosch FX, de Sanjose S, Munoz N, Combita AL, Coursaget P, Diaz M, Dolo A, van den Brule AJ, Meijer CJ. Risk factors of invasive cervical cancer in Mali. International journal of epidemiology, 2002; 31(1):202-9.
  10. Schmandt RE, Iglesias DA, Lu KH. Understanding obesity and endometrial cancer risk: opportunities for prevention. American Journal of Obstetrics & Gynecology. 2011; 205(6):518-25.
  11. Fabjani G, Kucera E, Schuster E, Minai-Pour M, Czerwenka K, Sliutz G, Leodolter S, Reiner A, Zeillinger R. Genetic alterations in endometrial hyperplasia and cancer. Cancer letters, 2002; 175(2):205-11.
  12. Benyuk VA, Kurochka VV, Vynyarskyi YM, Goncharenko VM. Diagnostic algorithm endometrial pathology using hysteroscopy in reproductive age women. Women Health (ZdorovyaZhinky), 2009; 6(42):54-6.
  13. Goncharenko VM, Beniuk VA, Kalenska OV, Demchenko OM, Spivak MY, Bubnov RV. Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age. EPMA Journal, 2013; 4(1):24.
  14. Nicolaije KA, Ezendam NP, Vos MC, Boll D, Pijnenborg JM, Kruitwagen RF, Lybeert ML, van de Poll-Franse LV. Follow-up practice in endometrial cancer and the association with patient and hospital characteristics: a study from the population-based PROFILES registry. Gynecologic oncology, 2013; 129(2):324-31.
  15. Giordano G, Gnetti L, Merisio C, Melpignano M. Postmenopausal status, hypertension and obesity as risk factors for malignant transformation in endometrial polyps. Maturitas, 2007; 56(2):190-7.
  16. Zaporozhan VN, Tatarchuk TF, Dubinina VG, Kosey NV, Diagnosis and treatment of endometrial hyperplastic processes. Reprod Endocrinol, 2012; 1(3):5-12.
  17. Bera H, Mukhopadhyay S, Mondal T, Dewan K, Mondal A, Sinha SK. Clinicopathological study of endometrium in peri and postmenopausal women in a tertiary care hospital in Eastern India. OSR-JDMS, 2014; 13:16-23.
  18. Giuntoli RL, Zacur HA, Goff B, Garcia RL, Falk SJ. Classification and diagnosis of endometrial hyperplasia. Offical Reprint from UpToDate. 2014 Jun.
  19. Farquhar CM, Lethaby A, Sowter M, Verry J, Baranyai J. An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding. American Journal of Obstetrics & Gynecology, 1999; 181(3):525-9.
  20. Jetley S, Rana S, Jairajpuri ZS. Morphological spectrum of endometrial pathology in middle-aged women with atypical uterine bleeding: A study of 219 cases. Journal of mid-life health, 2013;4(4):216.
  21. Topcu HO, Erkaya S, Guzel AI, Kokanali MK, Sarıkaya E, Muftuoglu KH, Doganay M. Risk factors for endometrial hyperplasia concomitant endometrial polyps in pre-and post-menopausal women. Asian Pac J Cancer Prev, 2014; 15(15):5423-5425.
  22. Kudesia R, Singer T, Caputo TA, Holcomb KM, Kligman I, Rosenwaks Z, Gupta D. Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma. American Journal of Obstetrics & Gynecology, 2014; 210(3):255-261.
  23. Epplein M, Reed SD, Voigt LF, Newton KM, Holt VL, Weiss NS. Risk of complex and atypical endometrial hyperplasia in relation to anthropometric measures and reproductive history. American journal of epidemiology, 2008; 168(6):563-70.
  24. Gregory CW, Wilson EM, Apparao KB, Lininger RA, Meyer WR, Kowalik A, Fritz MA, Lessey BA. Steroid receptor coactivator expression throughout the menstrual cycle in normal and abnormal endometrium. The Journal of Clinical Endocrinology & Metabolism, 2002; 87(6):2960-6.

 

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Imprint Cytology in the Diagnosis of Upper Gastrointestinal Lesions

Imprint Cytology in the Diagnosis of  Upper Gastrointestinal Lesions

*Keya  SA,1 Saha NK,2 Alam MJ,3 Ullah P,4 Shariar S,5 Hira AD,6 Ahmed NU,7 Islam N8

 Abstract

Endoscopic biopsy and cytology are well established techniques for the diagnosis of upper gastrointestinal tract malignances. Imprint cytology is a touch smear preparation which helps to diagnose malignant cell easily. This cross sectional study was done to see imprint cytological patterns of benign and malignant lesions of upper gastrointestinal tract,  to find out histopathological diagnoses and to compare imprint cytological diagnoses with histopathological diagnoses. Biopsy materials from 100 patients were obtained by endoscopist using video endoscope and were subjected to imprint smear technique followed by histopathological examination of the same materials. Cytological and histopathological diagnoses were compared using appropriate statistical methods. Among the 100 cases, 57(57%) were male & 43(43%) were female with a mean age of 56.7 years.  Out of 100 cases, gastric, esophageal and duodenal lesions were 63(63%), 32(32%) and 5(5%) respectively. Misinterpretation on cytological evaluation was seen in only 6 cases. The overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of imprint cytology were 98.46%, 91.42%, 95.52%, 96.97% and 96% respectively. The findings of the present study indicate that imprint cytological method is a reliable technique for rapid diagnosis of upper GIT lesions as it is simple, accurate and cost effective. Diagnosis can be provided within an hour of endoscopic procedure by the imprint smear technique.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):23-29]

 Keywords:  Imprint  cytology,  Upper  Gastrointestinal Lesions

 

  1. *Dr. Shamim Ara Keya, Lecturer of Pathology, Shaheed Suhrawardy Medical College, Dhaka. keyaparash@gmail.com
  2. Professor Dr. Naba Kumar Saha, Professor and Head, Department of Pathology, Sylhet MAG Osmani Medical College, Sylhet.
  3. Md. Jahangir Alam, Associate Professor and Head, Department of Gastroenterology, Sylhet MAG Osmani Medical College, Sylhet.
  4. Parash Ullah, Medical Officer, Department of Medicine, Shaheed Suhrawardy Medical College Hospital, Dhaka.
  5. Sakib Shariar, Pathologist, Bangladesh Railway Hospital, Chittagong.
  6. Ananda Dyuti Hira, Pathologist, Khulna Medical College, Khulna.
  7. Nasir Uddin Ahmed, Pathologist, Faridpur Medical College, Faridpur.
  8. Nazmul Islam, Assistant Professor of Pathology, Army Medical College, Comilla.

*For correspondence

Introduction

Any portion of the gastrointestinal tract may be affected by malignancy. The highest incidence of malignancy is in the esophagus, stomach and colorectal region. In fact esophagogastric and colorectal malignancies are amongst the commonest cancers in humans.1 Worldwide, gastric adenocarcinoma is the second most common cancer.2 Endoscopic biopsy and cytology are well established techniques for the diagnosis of upper gastrointestinal tract malignancies. Now a days, various cytologic techniques like brush cytology, crush preparation, touch smear or imprint cytology are commonly used along with routine endoscopic biopsy.3

Imprint cytology from endoscopic biopsy is highly sensitive and specific technique for the diagnosis of upper GI malignancy. Imprint cytology showed an overall accuracy of 97.6%, 100% and 100% for the diagnosis of malignancies of esophagus, stomach and duodenum respectively.4  But there is no systemic study on imprint cytology of gastrointestinal lesions in our country. Imprint cytology can act as an adjunct to histopathology as it increases the diagnostic efficacy and saves time but definitely it cannot replace histopathology as chances of false positives are high.5  Imprint cytology is a special variation of applied cytology that can be used for various purposes.6 Sometimes endoscopic biopsy fails to make a definitive histological diagnosis due to inadequate tissue from small lesion where tissues are distorted during histological processing; in that case imprint cytology may be useful in diagnosing upper gastrointestinal tract malignancy.7 In this study, imprint smears were taken before keeping the endoscopic specimens in fixative for histopathological examination. Endoscopic biopsy is an essential part of the evaluation of gastrointestinal pathology. In the diagnosis of upper GI lesions, histopathological examination is considered gold standard but is time-consuming  when compared to cytology. Most gastroenterologists and patients would like to get an immediate opinion regarding the adequacy of biopsy and nature of the lesion. Imprint cytology is a simple, rapid, reliable and cost effective method and it alone can serve as a useful tool for an immediate diagnosis within an hour after endoscopic procedure. Imprint cytology lets the surgeon to plan a therapeutic strategy approximately one week earlier.4,8  With this background, this study was designed to find out imprint cytological patterns of benign and malignant lesions of upper gastrointestinal tract, to find out histopathological diagnoses and to compare imprint cytological diagnoses with histopathological diagnoses.

 Methods

This study was a cross sectional study and carried out on 100 patients in the department of Pathology, Sylhet MAG Osmani Medical College, Sylhet in collaboration with the department of Gastroenterology, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh from 1st January 2015 to 31st December 2015. During endoscopic examination by using video endoscope, biopsy was taken. Imprint smears were prepared from all biopsy samples. Imprint smear was done by placing tissue on the slides from the biopsy forcep with the help of a fine needle.  After placing tissue on the slides, thin smears were prepared by gently rotating the tissue with the needle. Then smears were fixed in 95% ethyl alcohol and stained with Papanicolaou stain.The same tissue after smear preparation was collected for histopathological examination. The tissue was examined thoroughly in day light  with particular emphasis on number, colour, consistency, presence or absence of hemorrhage and necrosis. Tissue was embedded as such and was placed in bottle containing 10% formalin with proper tagging and was kept for overnight fixation.  Routine tissue processing with paraffin impregnation was done and sections were stained with haematoxylin and eosin. The diagnosis of upper gastrointestinal tract malignancy was done according to the cytopathological and histopathological findings and grading was done by WHO classification. Then imprint smear diagnosis was compared with the histopathological diagnosis. The efficacy of imprint cytology was determined by sensitivity, specificity, positive predictive value, negative predictive value and accuracy.

 Results

Among the 100 patients, the age ranged from 21 to 100 years with a mean of 56.7 years. In this study, 57(57%) were male and 43(43%) were female with male to female ratio of 1.33:1. The highest number of patients  30(30%) was in the age group 61-70 years followed by 27(27%) in 41-50 years age group & 21(21%) in 51-60 years age group. In our study, 63% (63 cases) were located in the stomach, 32 % (32 cases) were in the esophagus, and 5% (5 cases) were in the duodenum. The most common presenting symptoms were pain and vomiting in case of gastric lesions and dysphagia in case of esophageal lesions.

 

Table I:  Imprint cytology and corresponding histopathological diagnosis in contingency (cross) table

 Cytological diagnosis

 

 

  

 

 

No

  

Histopathological diagnosis

 T

 

o

 

t

 

a

 

 

l
Adenocarcinoma Squamous cell carcinoma Chronic non atrophic gastritis Suggestive of adenocarcinoma Chronic gastric ulcer Chronic duodenitis Dysplasia Suggestive of squamous cell carcinoma Chronic esophagitis Hyperplastic polyp Gastric adenoma
Adenocarcinoma 35 34 1 35
Squamous cell carcinoma 25 25 25
Chronic  gastritis 24 23 1 24
Suspicious of adenocarcinoma 5 4 1 5
Chronic gastric ulcer 3 3 3
Suspicious of squamous cell carcinoma 2 1 1 2
Chronic duodenitis 2 2 2
Normal findings 2 1 1 2
Chronic esophagitis 1 1 1
Dysplasia 1 1 1
Total 100 35 25 24 4 4 2 2 1 1 1 1 100

 

 

Ulcerative (41%) and ulceroproliferative lesions (41%) were the most common endoscopic findings.  Proliferative lesion was found in 17% of cases and benign polyp was noted in 1% of cases. In the present study, the most common lesion diagnosed by imprint cytology was adenocarcinoma (35%) followed by squamous cell carcinoma (25%) and chronic gastritis (24%) (Table-1). Histopathological evaluation revealed that the most common tumor was adenocarcinoma (35%) followed by squamous cell carcinoma (25%), chronic non atrophic gastritis (24%), suggestive of adenocarcinoma (4%), chronic gastric ulcer (4%), chronic duodenitis (2%),  dysplasia (2%) & suggestive of squamous cell carcinoma, chronic esophagitis, hyperplastic polyp, gastric adenoma  1 case each  (Table I).

Complete correlation between imprint cytological and histopathological diagnosis was obtained in 94(94%) cases (Table II) and 6 cases were misinterpreted on cytological examination. Out of six misinterpreted cases, two cases were diagnosed as normal findings on imprint smears which were subsequently diagnosed as adenocarcinoma in one case and chronic gastric ulcer in another case on histopathology. One case was diagnosed as adenocarcinoma on imprint smears which was subsequently diagnosed as chronic non atrophic gastritis on histopathology. Another one case was diagnosed cytologically as chronic gastritis was diagnosed histologically as hyperplastic polyp. Cytological diagnosis of suspicious of squamous cell carcinoma in one case was confirmed as moderate dysplasia by histopathology. Cytologically one case was interpreted as suspicious of adenocarcinoma which was diagnosed as gastric adenoma on histopathological examination.

 

Table II:  Correlation of histopathological and cytopathological diagnoses

 

Histopathological diagnosis No. of Cases Cytological correct diagnosis Percentage
Adenocarcinoma 35 34 97.05
Squamous cell carcinoma 25 25 100
Chronic nonatrophic gastritis 24 23 95.83
Suggestive of adenocarcinoma 4 4 100
Chronic gastric ulcer 4 3 75
Chronic duodenitis 2 2 100
Dysplasia 2 1 50
Suggestive of Squamous cell carcinoma 1 1 100
Chronic esophagitis 1 1 100
Hyperplastic polyp 1 0 0
Gastric adenoma 1 0 0
Total 100 94 94

Statistical evaluation of imprint cytology was done (Table III) and validity of imprint cytology like sensitivity, specificity, PPV, NPV and accuracy were found as 98.46%, 91.42%, 95.52%, 96.97% and 96% respectively (Table IV).

Table III:  Statistical evaluation of cytopathological diagnosis of 100 cases of  upper GIT lesions

 

Histopathological diagnosis                               Cytopathological Diagnosis
Disease positive (Malignant) Disease negative(Benign)
Positive(Malignant)

 

 65

 

 TP 64 FP 3
Negative(Benign)

 

 35

 

 FN 1 TN 32
Total 100 Total 65 Total 35

 

TP= True positive, TN= True negative, FP= False positive, FN= False negative.

 

Table IV:  Validity of cytopathological diagnosis of 100 cases of upper GIT lesions.

 

Sensitivity Specificity PPV NPV Accuracy
98.46% 91.42% 95.52% 96.97% 96%

 

 

 

 

 

 

Figure 1. Photomicrograph of imprint cytology of adenocarcinoma (Papanicolaou stain, x40).

 

 

 

 

 

Figure 2. Photomicrograph of imprint cytology of squamous cell carcinoma (Papanicolaou stain, x40).

 

 

 

 

 

 

Figure 3.  Photomicrograph imprint cytology of chronic gastritis (Papanicolaou’s stain, x40).

 

 

 

 

 

Figure 4. Photomicrograph of imprint cytology of gastric ulcer (Papanicolaou stain, x40).

Discussion

The primary role of gastrointestinal tract cytology is the detection of cancer. Gastrointestinal cytology is still in its early stages of development and few studies have described the role of brush cytology and imprint cytology in interpretation of upper GI biopsy.

The age of study patients ranged from 21 years to 100 years with a mean of 56.7 years.  Of the 100 patients, 57(57%) were male and 43(43%) were female with male to female ratio of 1.33:1.  This observation is similar to other studies who also observed that the frequency of gastrointestinal lesions was more in male.4,9  Highest number (30%) of gastrointestinal lesions were found in the age group 61 to 70 years followed by 27(27%) in 41 to 50 years age group and 21(21%) in the age group of 51 to 60 years which have consistence with the study of Vijayanarasimha D et al9  who observed highest number in fifth to seventh decades of life with a mean age of 55 years.  In the present study, 63% lesions were in the stomach, 32% were in the esophagus and 5% were in the duodenum which are also close to the findings of the  study  done by Vijayanarasimha D et al9  who observed that out of 110 cases, 52(47.3%) were gastric, 45(40.9%) were esophageal and 13(11.8%) were duodenal lesions. The clinical presentations of study patients were upper abdominal or epigastric pain, dysphagia, vomiting, anorexia, distended abdomen and sometimes abdominal mass.  Abdominal or epigastric pain was the commonest symptom in case of gastric and duodenal lesions and dysphagia in case of esophageal lesions. This clinical observation is similar to the clinical findings of the study done by Vijayanarasimha D et al.9 In our study, endoscopic findings of upper GIT lesion were ulcerative (41%), ulcero-proliferative (41%), proliferative (17%) and polypoid (1%).  In this study, among 100 cases of upper GIT lesions, 65(65%) were malignant and 35(35%) were benign. Diagnostic accuracy of imprint cytology of esophageal, gastric and duodenal lesions were 96.88%, 95.24% and 100% respectively which corresponds to or even better than some of the other studies.4,5,9,10,11 Histopathological evaluation of biopsies from 100 cases revealed that the most common lesion  was adenocarcinoma (35%) followed by squamous cell carcinoma(25%), chronic  non atrophic gastritis (24%), suggestive of adenocarcinoma(4%), chronic gastric ulcer (4%), chronic duodenitis (2%) and dysplasia (2%). Chronic esophagitis, hyperplastic polyp, gastric adenoma constituted  one case each.

Complete correlation between imprint cytological and histopathological diagnosis was obtained in 94(94%) cases and 6 cases were misinterpreted on cytological examination. One false negative case found in this study that was observed in gastric lesion. This false negative result may be due to subepithelial location of the lesion which was missed on imprint smear.  False negative diagnosis in imprint cytology was also observed in subepithelial lesions studied by Asha M et al.10 On endoscopic examination, ulceroproliferative lesion was seen in two cases in the gastric antrum. In one case, imprint cytology smears showed anaplastic epithelial cells and a diagnosis of adenocarcinoma was made. Histopathological examination showed chronic non atrophic gastritis and did not reveal any evidence of malignancy. Other case was interpreted as suspicious of adenocarcinoma by imprint smear which was subsequently diagnosed as gastric adenoma with dysplastic change by histopathology. On endoscopic examination, an ulceroproliferative lesion was seen at the lower end of esophagus which was interpreted as suspicious of squamous cell carcinoma on imprint smear but histopathological examination revealed moderate dysplasia. In the present study, three false positive diagnoses were made by imprint cytology. False positive diagnosis was also reported by other researchers and they concluded that the false positive diagnosis was due to regenerative atypia.9,11

The highest correlation (100%) was observed between imprint cytology and histopathology in the diagnosis of squamous cell carcinoma, suggestive of adenocarcinoma, suggestive of squamous cell carcinoma, chronic duodenitis and chronic esophagitis.

The overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of imprint cytology in the diagnosis of upper gastrointestinal lesions were 98.46%, 91.42%, 95.52%, 96.97% and 96% respectively which are similar to other studies.4,9

 Conclusion

The findings of the present study indicate that imprint cytology is a reliable technique for rapid diagnosis of upper GIT lesions as it is simple, accurate and cost effective. Diagnosis can be provided within an hour of endoscopic procedure by the imprint smear technique. So, gastroenterologist or surgeon can take a therapeutic decision approximately one week earlier.

References

  1. Conrad R, Castelino-Prabhu S, Cobb C, Raza A. Role of cytopathology in the diagnosis and management of gastrointestinal tract cancers. Journal of Gastrointestinal Oncology 2012; 3: 285-98.
  2. Zhang XF, Huang CM, Lu HS et al. Surgical treatment and prognosis of gastric cancer in 2613 patients. World Journal of Gastroenterology 2004; 10: 3405-08.
  3. Batra M, Handa U, Mohan H, Sachdev A. A Comparison of cytohistologic techniques in diagnosis of gastroesophageal malignancy. Acta Cytologica 2008; 52: 77-82.
  4. Sanjeevreddy M, Kittur SK, Jakareddy RB, Patil SY, Yelikar BR. Role of imprint cytology in the diagnosis of upper gastrointestinal tract lesions. Indian Journal of Public Health Research and Development 2013; 4: 190-95.
  5. Sharma P, Misra V, Singh PV, Misra SP, Gupta SC. A correlative study of histology and imprint cytology in the diagnosis of gastrointestinal tract malignancies. Indian Journal of Pathology & Microbiology 1997;40:139-146.
  6. Muller HA. Imprint cytology, advantages and possibilities. Entrez Pub Med 1976; 94: 7-10. [Online]
  7. Lal N, Bhasin DK, Malik AK, Gupta NM, Singh K, Mehta SK. Optimal number of biopsy specimens in the diagnosis of ca esophagus. Gut 1992; 33: 724-26.
  8. Cubukçu A, Gönüllü NN, Kaçar SO, Alponat A, Paksoy N. Imprint cytology in the endoscopic diagnosis of gastrointestinal malignancies. Hepatogastroenterology 2002; 49: 198-200.
  9. Vijayanarasimha D, Mahadevappa A, Manjunath GV, Sunila R. Imprint cytology: A diagnostic aid in interpretation of upper gastrointestinal endoscopic biopsies. Journal of Digestive Endoscopy 2014; 5: 144-148.
  10. Asha M, Divya V, Manjunath GV, Sunila R. Application of imprint cytology in interpretation of esophageal biopsies. Journal of Evolution of Medical and Dental Sciences 2013; 2: 4350-7.
  11. Mysorekar VV, Dandekar CP, Satyaprakash BS, Sarkar A. Role of imprint cytology in the diagnosis of gastrointestinal tract malignancies. Indian Journal of Pathology & Microbiology 2003; 46: 37- 43.

 

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Computed Tomogram Guided Fine-Needle Aspiration Cytology of Lung and Mediastinal Masses: A Study of 166 Cases

Computed Tomogram Guided Fine-Needle Aspiration Cytology of Lung and Mediastinal Masses: A Study of 166 Cases

*Alam MA,1 Islam MR,2 Haque MR,3   Nath SK4

 Abstract
Computed tomogram guided fine needle aspiration cytology (FNAC) is an important and useful investigation to differentiate between benign and malignant lesions of lung and mediastinum. To evaluate the lung and mediastinal masses and to analyze and compare the results with cytological findings, 166 patients were retrospectively studied who underwent CT guided FNAC over a period of January 2015 to December 2016. The study was carried out in patients who presented with respiratory symptoms with a localized lung and mediastinal masses which were confirmed by radiologically was sent for FNAC. 155 cases of lung masses and 11 cases of mediastinal mass were included in this study. Patients’ age ranged from 15 to 95 year and the male to female ratio was 4:1. Radiologically, out of 166 cases, 140 cases were diagnosed as malignant, 8 cases as benign and 18 cases as inflammatory lesions. Cytologically, 146 cases were diagnosed as malignant, 20 cases were benign inflammatory lesion. Most common lung malignancy was squamous cell carcinoma (72 cases) followed by adenocarcinoma (32 cases), small cell carcinoma (10 cases), large cell carcinoma (8 cases), 18 cases of lung metastasis were seen. Compared to biopsy, CT guided FNAC shortens the diagnostic interval and helps in differentiating lung malignancy into different cytopathological types which aids in proper management of the malignant lesion. Out of 11 mediastinal masses 6 cases were malignant lymphoma, 3 cases specific inflammatory lesions (tuberculosis) and 2 cases was non-specific inflammatory lesions.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):19-22]

Keywords: Computed tomogram, Cytology, Guided FNAC, Lung mass, Mediastinal mass.

 

  1. *Dr. Md. Ashraful Alam, Associate Professor, Department of Pathology, Rangpur Medical College. drashraful09@gmail.com
  2. Md. Rezaul Islam, Senior Consultant, Radiology & Imazing, Sadar Hospital, Nilphamari.
  3. Md. Rashedul Haque, Associate Professor, Department of Biochemistry, Rangpur Medical College.
  4. Professor Swapan Kumar Nath, Department of Radiotherapy, Rangpur Medical College.

 

* For correspondence

 Introduction

A Computed tomography (CT) guided fine needle aspiration cytology (FNAC) is a well known modality for characterization of mediastinal masses. CT guided FNAC of lung lesions is a well established technique for the cytologic diagnosis of peripheral malignant lung lesions, with a reported diagnostic accuracy rate more than 93% and a sensitivity rate less than 95%.1,2 It has been used to differentiate mediastinal masses into benign, malignant and inflammatory types. Furthermore, its use has been extended in differentiating lung malignancy into different cytopathological types which aids in proper management of the malignant lesions. CT guided FNAC is widely recognized technique in indeterminate mass. It is a simple diagnostic method of relatively low cost, with negligible mortality and limited morbidity.3 The accuracy of CT guided FNAC for discriminating benign from malignant lesion has been recorded to vary from 64% to 97%.4 Several post procedural complications have been reported for CT guided FNAC such as pulmonary hemoptysis and pneumothorax. The risk for developing pneumothorax has been observed to be 22% – 45% due to high sensitivity of CT in detecting pneumothorax.5 Relative contraindications to image guided FNAC are severe chronic obstructive airway disease, bleeding diathesis, contra lateral pneumonectomy and pulmonary arterial hypertension.6 The purpose of our study is to evaluate the accuracy of CT and CT guided FNAC in differentiating and recording the pathological spectrum of the mediastinal and lung masses.

 Methods

This is a retrospective study conducted in a private medical college hospital at Rangpur and two private laboratories in Rangpur city from Janary 2015 to December 2016.The study was carried out in 166 patients who presented with lung and mediastinal mass attended to different physicians and Rangpur Medical College Hospital and were sent for Fine needle aspiration cytology. Relevant clinical history and investigations were obtained from the patient to narrow down the differential diagnosis and to decide if patient was eligible for FNAC, such as history of bleeding diathesis, thrombocytopenia, dyspnea, uncontrolled cough, other feature of chronic obstructive airway diseases (COPD), pulmonary arterial hypertension etc. CT guided FNAC was performed in patients with peripheral lung and mediastinal mass or masses which were only approachable by spinal needle. Patient inclusion criteria included: cooperative patient who was able to hold breath for a short while, no bleeding tendency, patient who was to undergo chemo or radio-therapy and lesions not approachable by USG. Informed and written consent was taken from the patient explaining the risk and benefits of the procedure. Axial section of the area of interest was taken after a scanogram. A feasible approach was judged and the patient positioned accordingly with radiopaque marker placed at the site of puncture. Then under all aseptic precaution aspiration done by 21-22 G spinal needle and 10 cc disposable syringe and smear was prepared in glass slide for fixation in 95% alcohol. Routine Papaniculau stain were done in all cases.

 Results

The data were collected from January 2015 to December 2016. Our study included 166 patients, out of which 155 with lung and 11 with mediastinal mass were subjected to CT guided FNAC. Their ages ranged from 15 to 95 years with mean age of 65 years (Table I). The male to female ratio was 4:1. Out of 155 lung  malignant cases squamous cell carcinoma (Fig 1, 72 cases) was the commonest followed by adenocarcinoma ( fig 2, 32 cases), 10 cases of small cell carcinoma, 8 cases of large cell carcinoma were seen. Out of 18 cases of metastatic tumors, 10 cases were from gastrointestinal tract, 2 cases from testis and 6 cases from thyroid follicular carcinoma (Table IV). Out of 15 inflammatory cases 7 cases was specific inflammatory (tuberculosis) 8 cases was non- specific inflammatory lesion was observed. (Table IV). Out of 11 mediastinal masses 6 cases were malignant lymphoma,3 cases ware specific inflammatory lesions(tuberculosis) and 2 cases were non-specific inflammation was observed (Table V).

Table I: Age distribution (n=166)

Age Groups
(Years)		 Male Feamle Total %
15-25 6 3 9 5.42%
26-35 5 3 8 4.81%
36-45 13 4 17 10.42%
46-55 24 13 37 22.28%
56-65 30 12 42 25.30%
66-75 34 3 37 22.28%
>75 15 1 16 9.6%

 

Table II: Sites of the lesions (n=166)

Sites No %
Pulmonary 155 93.37
Mediastinal 11 6.62

Table III: Lung lesions by site and sex

 

Sex Site
Right Lung Left lung Total
Male 102(76.69%) 31(18.67%) 133(80.12%)
Female 20(60.60% 13(39.39%) 33(19.87%)
Total 122(73.49%) 44(26.50%) 166

 

Table IV: CT guided FNAC diagnosis of intrathoracic and mediastinal masses (n=166)

 

Cytological Findings: No(%)
Squamous cell carcinoma 72(43%)
Adenocarcinoma 32(19.27%)
Small cell carcinoma 10(6.02%)
Large cell carcinoma 8(4.81%)
Metastatic carcinoma 18(10.84%
Malignant Lymhoma 6(3.61%)
Specific Inflammatory lesions(TB) 10(6.02%)
Non specific inflammatory lesion 10(6.02%)

 

Table V: CT guided FNAC diagnosis of mediastinal masses (n=11)

 

Cytological Findings: No (%)
Malignant lymphoma 6(54.54%)
Specific Inflammatory lesion(TB) 3 (27.27%)
Non-specific inflammatory lesion 2(18.18%)

TB=Tuberculosis

 

 

 

 

 

 

Figure 1. Photomicrograph of sqamous cell carcinoma of lung (Cytopathology)

 

 

 

 

 

Figure 2. Photomicrograph of adeno carcinoma of lung (Cytopathology)

 Discussion

CT guided transthoracic FNAC is a safe and accurate means of diagnosing benign and malignant intrathoracic lesions. In this study, Out of 166 patients 5.42% were in the age group from 15-25 years and 25.30%were in the age group of 56-65 years which is not similar with the study of Sarker RN et. al 7 who found patients of intra-thoracic mass 36% in the age group ranging from 46-55 years and 21% in the age group of 56-65 years, these two groups were predominant in terms of age. There were 133  male (80.12%) and 33 female (19.67%). In the study of Sarker RN et. al7 out of 100 cases there were 77 men (77%) and 23 (23%) were women. This correlates with the well-known fact that intrathoracic mass occurs most commonly in older age group and in males than in females. Female cases are less because malignant pulmonary lesions are less in females in our population. Male: Female ratio was 4:1 in our study. That is similar to the study done by Ahmed et al.8 The locations of the pulmonary lesions were in right lung 122 (73.49%), and 44 (26.50%) in left lung. In the study of Ahamad et al8 lesion in right lung was 98 (60.49%), in left lung 64 (39.41). In the final diagnosis, squamous cell carcinoma was the commonest malignant tumour followed by adenocarcinoma and metastatatic carcinoma. These findings are similar to the findings of the study done by Mostafa et al9 although his study was not guided by CT and the number of cases was less. Our experience is similar to the study of Singh et al10 where fatal complications like tension pnemothorax, air embolism, endo bronchial haemmorhage etc were absent. The complication rate depends on the distance of the lesion from pleura and lesion size. The more the amount of the lung tissue traversed by the needle the more was the complication rate and smaller the lesion the more was the complication rate. In this study fine needle of 21- 22G was used where the chance of complication seems to be minimum which correlates well with the study of Zavala et al.11  Saha A et al12 in their series have reported cases of mediastinal masses, 3 (5.6%) cases was NHL and (1cases) was Hodgkin’s lymphoma.In our study 6 cases (54.54%) was malignant lymphoma. This discrimination may be due to total number of cases.

Conclusion

This study concludes that CT guided lung and mediastinium needle aspiration cytology by spinal needle is a highly effective procedure in the diagnosis and sub- classification of mass lesions. It is a relatively simple, cost effective procedure with good patient compliance and low morbidity. The use of CT-guided FNAC of intrathoracic mass lesions reduces the diagnostic interval and cost. It also avoids unnecessary thoracotomy for diagnostic purposes. As the facilities continue to improve; it is likely to have a greater role in the initial evaluation of intrathoracic and mediastinal mass in the near future.

 References

  1. Wallace MJ, Krishnamurthy S, Broemeling LD, Gupta S,Ahrar K, Morello FA Jr, et al. CT-guided percutaneous fine needle aspiration biopsy of small (<1 cm) pulmonary lesions. Radiology 2002; 225:823-8.
  2. Laurent F, Latrabe V, Vergier B, Mountadon M, MernejouxJM, Dubrez J. CT-guided transthoracic needle biopsy of pulmonary nodules smaller than 20 mm: results with an automated 20-gauge coaxial cutting needle. Clin Radiol 2000; 55:281-7.
  3. Santambrogio L, Nosotti M, Bellaviti N et al. CT Guided Fine Needle Aspiration Cytology of Solitary Pulmonary Nodules. Chest1997; 112:423-5.
  4. Mohammad GM. CT guided fine needle aspiration cytology in diagnosis of thoracic lesions. JIMA 2001; 99(10):1-5.
  5. Herman PG, Hessel SJ. The diagnostic accuracy and complications of closed lung biopsies. Radiology 1977; 125:11-4.
  6. Hensell DM: Interventional techniques. In Armstrong P,Wilson AG, Dee P, et al (eds): Imaging Of Diseases Of TheChest. 2nd ed . St. louis, Mosby, 1995, p. 894-912.
  7. Sarker RN, Rabbi AF, Hossain A, Quddus MA, Chowdhury N, Sarker T. Computed tomography guided transthoracic fine needle aspiration cytology in the diagnosis of Sonographically non-approachable intrathoracic masses-A study of 100 cases.J Dhaka Med Coll 2011; 20(1):25-31.
  8. Ahmed S, Ahamad M S U. Computed tomography guided fine needle aspiration cytology of lung lesions: A study of162 cases. JCMCTA 2009; 20 (1):50-2.
  9. Mostafa MG. Computed tomographic guided fine needle aspiration cytology in the diagnosis of thoracic lesions. J Indian Med Assoc 2001; 99(10): 550-3.
  10. Singh JP, Garg L, Setia V. Computed tomography (CT) guided transthoracic needle aspiration cytology in difficult thoracic mass lesions – not approachable by USG. IJRI, 2004; 14(4):395-400.
  11. Zavala DC, Bedell GN. Transthoraciclung biopsy with a cutting needle. Am Rev Respir Dis 1972; 106: 186-93.
  12. Saha A, Kumar K, Choudhuri M K. Computed tomography – guided fi ne needle aspiration cytology of thoracic mass lesions: A study of 57 cases. J cytol 2009; 26 (2):55-9.