Original article / research
| Year :
2023 |
Month :
October
|
Volume :
12 |
Issue :
4 |
Page :
PO21 - PO24 |
Full Version
|
|
Distribution of Mast Cells in Uterine Leiomyoma and Adjacent Myometrium: A Cross-sectional Study
|
D Shobhitha, Shankar Saranya, Yadav M Dileep, Anikode Subramanian Ramaswamy
1. Assistant Professor, Department of Pathology, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India.
2. Assistant Professor, Department of Pathology, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India.
3. Civil Assistant Surgeon Specialist-Pathology, Department of Pathology, Area Hospital, Yerragundapalem, Andhra Pradesh, India.
4. Professor and Head, Department of Pathology, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India.
|
| |
Correspondence
Address :
D Shobhitha, Shankar Saranya, Yadav M Dileep, Anikode Subramanian Ramaswamy,
Dr. D Shobhitha,
No. 115, Yahvi, Sindhu Layout, Robertsonpet, Kolar Gold Fields-563122 Karnataka, India.
E-mail: kgfshobhitha@gmail.com
|
| | | ABSTRACT |  | : Introduction: Mast cells are involved in various physiological and pathological processes. Their role in neoplasm angiogenesis remains an enigma. Mast cells have been observed in association with smooth muscle tumours of the uterus. The role of mast cells in leiomyomas is conflicting, with some studies favoring tumour development and others showing the opposite.
Aim: To assess the distribution of mast cells in uterine leiomyomas and the adjacent myometrium.
Materials and Methods: This cross-sectional study included 100 consecutive hysterectomy specimens from patients who underwent surgery for leiomyoma over a period of one year and five months at PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India. Sections from the leiomyoma and adjacent myometrium were stained with Hematoxylin and Eosin (H&E) and toluidine blue stains. Mast cell distribution was calculated. The data was collected and analysed using the Statistical Package for the Social Sciences (SPSS) (Version 23.0; SPSS Inc., Chicago, IL, USA). Mast cell counts were expressed as mean and standard deviation. The comparison between the means of different groups was performed using the “Independent sample t-test.” A p-value<0.05 was considered statistically significant.
Results: A total of 100 leiomyoma cases were included in the study. The mean age of the study participants who underwent hysterectomy was 46.3±6.73 years, and the majority (32%) of them were in the age group of 46-50 years. The average number of mast cells in the leiomyoma and adjacent myometrium was 11.65±15.813 and 37.16±23.008, respectively. A statistically significant difference was observed between leiomyoma and adjacent myometrium (p-value<0.0001).
Conclusion: A higher distribution of mast cells was observed in the myometrium adjacent to the leiomyoma. This finding may indicate that mast cells play a role in the growth of leiomyoma by providing appropriate growth factors. |
 |
| Keywords
: Benign tumours, Degenerations, Mast cell density, Smooth muscle tumours, Uterus |
|
| DOI and Others
: DOI: 10.7860/NJLM/2023/64426.2770
Date of Submission: Apr 02, 2023
Date of Peer Review: May 06, 2023
Date of Acceptance: Jul 19, 2023
Date of Publishing: Oct 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Apr 06, 2023
• Manual Googling: Jul 14, 2023
• iThenticate Software: Jul 18, 2023 (24%)
ETYMOLOGY: Author Origin
EMENDATIONS: 7 |
|
| |
|
INTRODUCTION |
|
Mast cells were first described by Paul Ehrlich in 1878 (1). Over the past two decades, mast cells have gained recognition for their involvement in physiological and pathological processes (2). They play a role in physiological processes such as inflammation, angiogenesis, wound healing, fibrosis, tissue remodeling, as well as pathological conditions like asthma. Additionally, they contribute to the pathogenesis of various benign and malignant lesions affecting different organ systems (1).
Mast cells are components of the cancer microenvironment and are present in peri- and intratumour sites. Upon stimulation, mast cells release enzymes such as histamine, tryptase, chymase, Vascular Endothelial Growth Factors (VEGFs), Tumour Necrosis Factor α (TNF-α), Matrix Metalloproteinases (MMPs), Fibroblast Growth Factors (FGFs), Transforming Growth Factor-β (TGF-β), and interleukins, which have protumourigenic and antitumourigenic responses (3). Several types of tumour cells exhibit increased production of stem cell factor, which stimulates mast cell migration, proliferation, and degranulation (4). Literature reports a close correlation between mast cells and angiogenesis in neoplasms. Mast cells have been observed around the periphery of the tumour, in the adjacent connective tissue, and near lymphatics and blood vessels. It is suspected that they play a role in tumour development, progression, and angiogenesis (4). The presence of mast cells in tumours has also been described as evidence of host immunologic antitumour response by inhibiting tumours through cytotoxic factors like TNF-α and granzyme B (3). The accumulation of mast cells may be part of a generalised inflammatory reaction described in some tumours (5).
In the uterus, mast cells have been reported in the myometrium and uterine smooth muscle tumours (6). Most of them were observed in close association with uterine smooth muscle cells, as well as in the vicinity of fibroblasts and collagen, suggesting they may play an important role in the reconstruction of uterine tissues during the menstrual cycle (2).
The significance of mast cells in non-neoplastic and neoplastic lesions of the uterus and cervix has been studied with conflicting results. Mast cells have been hypothesized to enhance tumour development based on their effects on angiogenesis. However, there is also mounting evidence suggesting that mast cells inhibit tumours (4). In lesions of the cervix, Kalyani R and Rajeshwari G found a decreased number of mast cells in neoplastic lesions compared to non-neoplastic lesions (2). In lesions of the uterus, although evidence exists that mast cells promote tumourigenesis, there are some clinical settings and experimental tumour models that suggest mast cell functions favoring the host (7). Thus, the effect of mast cells on uterine leiomyomas is still unclear. Therefore, the present study was conducted in an attempt to determine the role of mast cells in uterine leiomyomas. A study by Abeyratne NV et al. found a low mast cell count in leiomyomas with hyaline degeneration. Since there are very few studies in the literature (8) exploring the distribution of mast cells in leiomyomas with degeneration, the present study aimed to compare the mast cell distribution in uterine leiomyoma with the adjacent myometrium and also compare the mast cell distribution in various degenerations in leiomyoma.
|
| |
| |
|
Material and Methods |
|
This was a cross-sectional study of 100 consecutive hysterectomy specimens operated for leiomyoma and received in the Department of Pathology, PES Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India. The study was conducted over a period of 17 months, from February 2019 to July 2020. This study was approved by the Institutional Human Ethics Committee (PESIMSR/IHEC/C-12/2022). Histopathological examination was conducted in the Department of Pathology.
Inclusion criteria: All hysterectomy cases with uterine leiomyomas were included in the study.
Exclusion criteria: Specimens consisting of autolyzed or necrosed tissue and non-appreciable myometrial tissues were excluded from the study.
Procedure
Two sections each were taken from the leiomyoma and its adjacent myometrium. These sections were routinely processed using formalin fixation and paraffin embedding. The obtained blocks were cut into 4 μm sections and stained with H&E stain for routine examination (shown in (Table/Fig 1),(Table/Fig 2)) and 1% toluidine blue stain as per routine protocol for the detection of mast cells (9). Toluidine blue stains mast cell granules in a purple to red color (shown in (Table/Fig 3),(Table/Fig 4)).
Mast cells were counted under 40X magnification for 10 consecutive fields in each slide in areas where the maximum number of mast cells were observed. The number of mast cells per 10 high-power fields (hpf) in the leiomyoma was compared with the adjacent myometrium. The mast cell distribution in leiomyomas with degenerations was recorded and compared. The distribution of different degenerations among the leiomyoma specimens, the mean and standard deviation of mast cells among the leiomyomas and their adjacent areas, and the mean and standard deviation of mast cells among degenerative and non-degenerative leiomyomas were determined in this study.
Statistical Analysis
The study details were collected, and the data was entered into MS Excel 2010. Further analysis was performed using Statistical Package for the Social Sciences (SPSS) (Version 23.0; SPSS Inc., Chicago, IL, USA). The mast cell counts were expressed as mean and standard deviation. The comparison between the groups was conducted using the "independent sample t-test". A p-value < 0.05 was considered statistically significant.
|
| |
| |
|
Results |
|
There were a total of 100 leiomyoma cases. The mean age of the study participants who underwent hysterectomy was 46.3±6.73 years, and the majority (51%) of them were in the age group of 41-50 years (shown in (Table/Fig 5)).
Distribution of leiomyoma cases is depicted in (Table/Fig 6).
The average number of mast cells in the leiomyoma and adjacent myometrium was 11.65±15.813 and 37.16±23.008, respectively. A statistically significant difference was noted between the two groups (p-value: <0.0001) (shown in (Table/Fig 7)).
The average number of mast cells in the leiomyoma and adjacent myometrium of leiomyoma with degeneration is shown in (Table/Fig 8).
Among the 36 cases displaying degeneration, 34 cases had hyaline degeneration (including leiomyomas with hyaline degeneration-27 and leiomyoma with adenomyosis with hyaline degeneration-7), and 2 cases had myxoid degeneration. The average number of mast cells in the adjacent myometrium of uterine leiomyoma with hyaline degeneration and myxoid degeneration was 39 and 27 per 10 hpf, respectively (shown in (Table/Fig 9)).
|
| |
| |
|
Discussion |
|
Mast cells are present in virtually all vascularised tissues (10). Derived from the bone marrow, mast cells are tissue-homing leukocytes that were initially described by Paul Ehrlich over 130 years ago (10). The role of mast cells has been a puzzle for researchers. Cajal noted their close association with some epithelial tumours, suggesting their importance in the host defense mechanism (11). They are known to be involved in the pathogenesis of allergic reactions and responses to parasitic tissue (11). However,
recent studies have recognised their significant role in tumour development (12). The major link between mast cells and cancer is their ability to secrete potent angiogenic compounds (13). A study by Jiang L et al., suggests that mast cell count may be a useful indicator in differentiating between leiomyomas and leiomyosarcomas (7). The stroma surrounding tumour tissue is believed to contain mast cells that secrete angiogenic cytokines and proteases (14). Many tumours have been found to have a high number of mast cells (15). The human uterus, especially the myometrium, is considered relatively rich in mast cells compared to other tissues in the body. These mast cells are located in proximity to smooth muscle cells and connective tissue (1). Few studies have explored the relationship between mast cells and leiomyoma in general, and specifically in leiomyomas with degeneration (1),(4),(7). Therefore, one of the objectives of this study was to compare the distribution of mast cells in various degenerations in leiomyoma, making it a unique study.
In the present study, a statistically significant difference (p-value <0.001) was observed in the mean mast cell count between uterine leiomyomas and adjacent myometrium. The average number of mast cells per 10 hpf in uterine leiomyoma was 11.65, while in the adjacent myometrium, it was 37.16. These results are consistent with similar studies that have reported the proportional distribution of mast cell numbers. For example, Apurva V et al., found 40 mast cells in the myometrium per 10 hpf (1), Gousuddin M et al., found 85.5 mast cells in the myometrium per 10 HPF, Orii A et al., found 37 mast cells in the myometrium per 10 HPF, and Erol AY et al., found 41 mast cells in the myometrium per 10 HPF (Table/Fig 10) (1),(4),(11),(12). However, direct comparison of mast cell numbers may not be possible due to the limited number of leiomyoma cases available for analysis and the limited number of tissue sections examined, which may not capture the full spectrum of mast cell distribution. The observation of a greater number of mast cells in the myometrium adjacent to the leiomyoma further supports the suspicion that these cells may play a role in tumour angiogenesis (4).
The average number of mast cells per 10 hpf in uterine leiomyoma with degeneration and in the adjacent myometrium was 12.181 and 36.931, respectively. A decreasing trend in the mean number of mast cells in the adjacent myometrium of uterine leiomyoma with degeneration was observed.
A study by Abeyratne NV et al. found a low mast cell count (<50/10 hpfs) in leiomyomas with hyaline degeneration (8). As there have been limited studies conducted in this regard, further research is suggested to ascertain the probable explanation for low mast cell counts in cases of leiomyomas with degeneration.
Erol AY and Ozdemir O conducted a study on the correlation between Microvessel Density (MVD) and Mast Cell Density (MCD) and found no significant correlation between MVD and MCD in leiomyomas. They suggested that the presence of mast cells would indicate the benign nature of myometrial lesions, which may be important in the assessment of malignant and premalignant lesions (16).
Limitation(s)
The study was limited by the number of leiomyoma cases available for analysis. Histomorphological assessment of mast cells involves subjective interpretation by pathologists, which may have led to interobserver variability.
|
| |
| |
|
Conclusion |
|
It was observed that there was a higher distribution of mast cells in the myometrium adjacent to the leiomyoma. This may indicate that they play a role in the growth of leiomyoma by providing appropriate growth Factors. The presence of mast cells may indicate the benign nature of myometrial lesions, which could be important in assessing malignant and premalignant lesions.
Further studies on mast cell distribution may shed additional light on the role of mast cells in tumour biology.
|
| |
| |
|
Acknowledgement |
|
|
We would like to thank the histopathology technicians in the Department of Pathology, PESIMSR, Kuppam, Andhra Pradesh, India.
|
| |
| | 1. | Apurva V, Sharma PK, Manchanda GS, Sharma VK, Sood S, Vats S. Mast cell profile in myometrial lesions: A study of 577 cases. Indian Journal of Basic and Applied Medical Research. 2016;5(2):646-50.
[ Google Scholar] | | 2. | Kalyani R, Rajeshwari G. Significance of mast cells in non-neoplastic and neoplastic lesions of uterine cervix. Biomedical Research and Therapy. 2016;3(1):469-75. ?doi?https://doi.org/10.7603/s40730-016-0003-y#doi#
[ Google Scholar] [ CrossRef] | | 3. | Komi DEA, Redegeld FA. Role of mast cells in shaping the tumour microenvironment. Clin Rev Allergy Immunol. 2020;58(3):313-25. ?doi?https://doi.org/10.1007/s12016-019-08753-w#doi#?pmid?31256327#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 4. | Erol AYG, Tokyol C, Ozdemir O, Yilmazer M, Arioz TD, Aktepe F. The role of mast cells and angiogenesis in benign and malignant neoplasms of the uterus. Pathol Res Pract. 2011;207(10):618-22. ?doi?https://doi.org/10.1016/j.prp.2011.07.002#doi#?pmid?21820813#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 5. | Erol AYG, Ozdemir O. Mast cells: Are they really related to invasiveness of endometrial carcinoma? Pathology-Research and Practice. 2010;206(6):426-28. ?doi?https://doi.org/10.1016/j.prp.2009.12.007#doi#?pmid?20188490#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 6. | Cinel L, Aban M, Basturk M, Ertunc D, Arpaci R, Dilek S, et al. The association of mast cell density with myometrial invasion in endometrial carcinoma: A preliminary report. Pathol Res Pract. 2009;205(4):255-58. ?doi?https://doi.org/10.1016/j.prp.2008.10.011#doi#?pmid?19091488#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 7. | Jiang L, Hua Y, Shen Q, Ding S, Jiang W, Zhang W, et al. Role of mast cells in gynecological neoplasms. Front Biosci (Landmark Ed). 2013;18(2):773-81. ?doi?https://doi.org/10.2741/4140#doi#?pmid?23276962#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 8. | Abeyratne NVA, Santos LD, Yong LYC. A study of distribution of mast cells in uterine leiomyomas and myometrium and their relationship to morphology of leiomyomas and patients’ clinical features. Pathology-Journal of the RCPA. 2015;47:S101. ?doi?https://doi.org/10.1097/01.PAT.0000461610.11772.fe#doi#
[ Google Scholar] [ CrossRef] | | 9. | Suvarna KS, Layton C, Bancroft JD. Bancroft’s theory and practice of histological techniques E-Book. Elsevier health sciences. 2018.
[ Google Scholar] | | 10. | Ribatti D. The staining of mast cells: A historical overview. Int Arch Allergy Immunol. 2018;176(1):55-60. ?doi?https://doi.org/10.1159/000487538#doi#?pmid?29597213#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 11. | Gousuddin M, Roohi S, Pattankar VL. Common lesions of uterus and cervix with mast cell profile. Asian Pac J Health Sci. 2015;2(1):105-07. ?doi?https://doi.org/10.21276/apjhs.2015.2.1.19#doi#
[ Google Scholar] [ CrossRef] | | 12. | Orii A, Mori A, Zhai YL, Toki T, Nikaido T, Fujii S. Mast cells in smooth muscle tumours of the uterus. Int J Gynecol Pathol. 1998;17(4):336-42. ?doi?https://doi.org/10.1097/00004347-199810000-00007#doi#?pmid?9785134#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 13. | Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. iochim Biophys Acta. 2012;1822(1):02-08. ?doi?https://doi.org/10.1016/j.bbadis.2010.11.010#doi#?pmid?21130163#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 14. | Guidolin D, Marinaccio C, Tortorella C, Annese T, Ruggieri S, Finato N, et al. Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma. Clin Exp Med. 2017;17(1):71-77. ?doi?https://doi.org/10.1007/s10238-016-0407-4#doi#?pmid?26886279#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 15. | Ghouse SM, Polikarpova A, Muhandes L, Dudeck J, Tantcheva-Poór I, Hartmann K, et al. Although abundant in tumour tissue, mast cells have no effect on immunological micro-milieu or growth of HPV-induced or transplanted tumours. Cell Rep. 2018;22(1):27-35. ?doi?https://doi.org/10.1016/j.celrep.2017.12.010#doi#?pmid?29298428#pmid#
[ Google Scholar] [ CrossRef] [ PubMed] | | 16. | Erol AYG, Ozdemir O. Do mast cell phenotypes play a role in concomitantly increased microvessel density and progression of non-small cell lung cancer? Human Pathology. 2011;7(42):1056-57.?doi?https://doi.org/10.1016/j.humpath.2011.01.031#doi#?pmid?21683868#pmid# [ Google Scholar] [ CrossRef] [ PubMed]
|
|
| |
| TABLES AND FIGURES | |
|
| |
|
|
|