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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 12  |  Issue : 3  |  Page : 131-134

Synchronous primary malignancies and pre-cancers affecting entire hysterectomy specimen: A report of an unfortunate case


1 Department of Pathology, AIIMS, Patna, Bihar, India
2 Department of Hematology (Pathology), IGIMS, Patna, Bihar, India
3 Department of Radiation Oncology, AIIMS, Patna, Bihar, India

Date of Submission15-Sep-2021
Date of Decision07-Mar-2022
Date of Acceptance14-Mar-2022
Date of Web Publication30-Jun-2022

Correspondence Address:
Dr. Iffat Jamal
Marina Heights Apartment, A.G. Colony, Patna - 800 025, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_94_21

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  Abstract 


Synchronous tumours of the female genital tract are rare, accounting for approximately 1%–2% of all gynaecological malignancies involving simultaneous independent primary malignancies. Synchronous tumours in the ovary and endometrium are the most common combination. We report on a 58-year-old postmenopausal woman who presented with bleeding per vaginum for 1.5 months with no prior menstrual complaints. On per vaginal examination, a mass was felt in the pelvis. Ultrasonography revealed a mass of 8 cm × 9 cm in size filling the entire uterine cavity. Contrast enhanced computed tomography showed a multilobate mass in the pelvis, replacing the whole uterus and cervix, with heterogeneous enhancement and internal necrosis. Bilateral ovaries were not visualised separately. The radiological impression suggested an endometrial carcinoma. Wertheim's hysterectomy was subsequently performed. On microscopic examination, the uterine mass revealed a malignant mixed Müllerian tumour (carcinosarcoma) of the endometrium, along with a high-grade serous carcinoma of the left ovary and left fallopian tube. The right fallopian tube showed adenocarcinoma in situ. The patient had an unusual past history of multiple system comorbidities, a few of which were continuing and for which she was receiving medical treatment.

Keywords: Carcinosarcoma, complex and mixed, Müllerian tumour, neoplasms, synchronous


How to cite this article:
Bharti S, Jamal I, Singh P. Synchronous primary malignancies and pre-cancers affecting entire hysterectomy specimen: A report of an unfortunate case. Curr Med Res Pract 2022;12:131-4

How to cite this URL:
Bharti S, Jamal I, Singh P. Synchronous primary malignancies and pre-cancers affecting entire hysterectomy specimen: A report of an unfortunate case. Curr Med Res Pract [serial online] 2022 [cited 2022 Aug 12];12:131-4. Available from: http://www.cmrpjournal.org/text.asp?2022/12/3/131/349300




  Introduction Top


About 1%–2% of all gynaecological cancers are synchronous tumours with two or more simultaneous independent primary tumours.[1] These synchronous tumours are either identical or entirely different in histomorphology. Strict histomorphological and immunohistochemical analyses are necessary to distinguish multiple primary tumours from tumours that have metastasized from one site to another.[2] Here, we present a case of a synchronous presence of tumours of different types arising from various sites involving the female genital system, along with an unusual history of multiorgan system comorbidities.


  Case Report Top


A 58-year-old postmenopausal woman presented with bleeding per vaginum for over a month, with a recent development of overflow incontinence for around 10 days. The patient did not provide a history of any prior menstrual complaints. She had a past medical history of multiple site fractures, including of the right wrist and left leg. She had suffered from pulmonary tuberculosis, for which she received antitubercular treatment for a year. She presented with a history of hypothyroidism and hypertension for around a decade and was irregularly taking medicines for these conditions. Per vaginal examination revealed a uterus of 10 weeks gestational size with a soft mass felt in the pelvis. Per speculum examination showed the unhealthy hypertrophied cervix.

The uterus measured 11 cm × 8 cm on ultrasonography, with a large, multilobulated solid mass that was isoechoic to the myometrium and had increased internal vascularity. Computed tomography of the pelvis revealed a well-demarcated mass replacing the uterus and cervix with necrosis and fluid collection. The ovaries were not seen separately. Radiological interpretation suggested a malignant mass, probably endometrial carcinoma [Figure 1]a and [Figure 1]b. Routine serum tumour markers were within normal limits except for a slightly elevated CA-125 level of 82 IU/ml. Routine haematological parameters were unremarkable except for a moderate degree of anaemia. A Wertheim's hysterectomy was performed and sent for histopathology. Macroscopically, the entire endometrial cavity was filled with a large polypoidal and friable growth measuring 8 cm × 6 cm × 5 cm, with thinning of the myometrium. The attached right  Fallopian tube More Details was dilated, with obliteration of the lumen. The right ovary was unremarkable grossly. The left ovary and left fallopian tube were received in a separate container in multiple greyish white, friable tumour fragments [Figure 1]c and [Figure 1]d.
Figure 1: (a) Computed tomography pelvis revealed a well-demarcated mass in pelvis replacing uterus and cervix with necrosis and fluid collection. (b) Computed tomography pelvis revealed a large endometrial mass adhered to bilateral ovaries and other adjacent pelvic structures. (c) Gross image of large polypoidal and friable growth measuring 8 cm × 6 cm × 5 cm in endometrial cavity. Attached right fallopian tube was dilated with obliteration of the lumen. The right ovary was unremarkable. The left ovary and fallopian tube were received in a separate container which showed multiple greyish white, friable fragments. (d) Gross image showing adhered and distorted right fallopian tube forming a tubo-ovarian mass

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Microscopic examination of representative sections revealed a spectrum of malignancies of varied morphologies affecting different parts of the specimen received. The morphological diagnoses offered were as follows:

  • Uterus: Malignant mixed Müllerian tumour involving the endomyometrium
  • Cervix: High-grade squamous intraepithelial lesion)
  • Right fallopian tube: Adenocarcinoma in situ
  • Left ovary and left fallopian tube: Serous cystadenocarcinoma, high-grade [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d,[Figure 2]e,[Figure 2]f.
Figure 2: (a) Microphotograph showing biphasic tumour with epithelial and sarcomatous components (H and E, ×400). (b) Microphotograph showing heterologous cartilaginous elements in the stroma (H and E, ×400). (c) Microphotograph showing features of high-grade serous carcinoma of the left ovary (H and E, ×400). (d) Microphotograph showing moderate ectocervical dysplasia (CIN II). Insight shows features of adenocarcinoma in situ of the right fallopian tube. (e-i) Microphotograph of IHC images showing positivity for strong positivity for CK7, patchy positive for P53, ER, diffuse strong positivity for Vimentin and increased Ki-67 (DAB, ×400)

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Other pathological parameters were reported according to the College of American Pathologists guidelines for reporting malignant uterine tumours and malignant ovarian tumours.

Immunohistochemistry (IHC) with a panel of markers was applied to both the left ovarian and the endometrial tumour. Common IHC markers applied on both these tumours were CK7, CK20, WT1, p53, PAX8 and Ki67. In addition, PAX8 IHC was done for the left ovarian mass, while vimentin and oestrogen receptor were applied to the endometrial tumour. The results of the IHC markers are presented in [Table 1], followed by the representative microphotographs in [Figure 2]e,[Figure 2]f,[Figure 2]g,[Figure 2]h,[Figure 2]i. The overall immunohistochemical features confirmed the presence of high-grade papillary serous carcinoma of the left ovary and an endometrial origin tumour showing carcinosarcomatous morphology with a strong WT1 positivity in tumour cells compared with that of left ovarian tumour.
Table 1: Results of immunohistochemistry markers applied on both left ovarian tumour and endometrial tumour

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  Discussion Top


In patients with synchronous primary tumours of the female genital tract, the tumours behave differently compared with individual primary tumours of fallopian tube, endometrium, cervix or ovary. However, it is challenging to confirm whether there are two or more different primary tumours present simultaneously at different sites or whether it is only an extension of one type of tumour to other sites.

Axelrod et al., Eisner et al., and Ayhan et al.[3],[4],[5] detected synchronous primaries among 1.8%, 0.7% and 1.7% of women with gynaecological neoplasms, respectively. Ayhan et al.[5] determined endometrial–ovarian synchronous tumours in 51.7% of women. Eifel et al. and Ziano et al.[6],[7] found a younger than expected median age in cases of synchronous tumours. Eifel et al.[6] also found that 50% of women with synchronous endometrial–ovarian tumours were nulliparous, with a considerable frequency of hypertension and diabetes mellitus (33.3% for each). However, we could not establish any correlation of patients' multiple comorbidities with the development of synchronous primaries in her genital system.

It is suggested that patients with synchronous primary tumours are likely to have hereditary cancer syndromes associated with familial mutations; however, this still needs to be validated and could not be determined in our case. Soliman et al.[8] found that 46% of women with synchronous endometrial and ovarian tumours present with abnormal uterine bleeding and 17% with abdominal or pelvic pain; these symptoms were also present in our case.

A similar case report by Jain and Puri showed a primary synchronous uterine carcinosarcoma with serous carcinoma of bilateral ovaries in a 63-year-old woman.[9] Three different types of uterine malignancies (carcinosarcoma, uterine papillary serous carcinoma and endometrioid carcinoma) in one patient have similarly been reported in the literature. We could clearly differentiate the separate origins of the left ovarian and endometrial malignancies. In addition, our patient had a high-grade dysplasia of the uterine cervix and of the right fallopian tube mucosa.

Generally, uterine carcinosarcomas reveal more aggressive behaviour compared with high-risk endometrioid carcinomas because of their distinct biologic characteristics, such as greater expression of IGF2 and lower expression of MUC1 and HOXB6. Based on microarray analysis of endometrioid carcinomas, uterine serous papillary carcinoma and uterine carcinosarcomas may develop in part through alternate genetic pathways.[10],[11]


  Conclusion Top


Synchronous primary genital tumours are supposed to have a better prognosis than tumours of single metastatic lesions because they are diagnosed at an earlier stage and are of low grade at the time of presentation. It is important to differentiate independent synchronous primary tumours from metastasis because the prognosis and clinical management vary between them. Complete morphological, immunohistochemical and molecular genetic evaluations, if available, need to be performed for confirmation, as well as a prognostication of these entities. Multiple past histories of fractures, tuberculosis, hypothyroidism and hypertension in this patient were not attributable to the occurrence of these synchronous primary malignancies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Singh N. Synchronous tumours of the female genital tract. Histopathology 2010;56:277-85.  Back to cited text no. 1
    
2.
Kanthan R, Senger JL. Uterine carcinosarcomas (malignant mixed müllerian tumours): A review with special emphasis on the controversies in management. Obstet Gynecol Int 2011;2011:470795.  Back to cited text no. 2
    
3.
Axelrod JH, Fruchter R, Boyce JG. Multiple primaries among gynecologic malignancies. Gynecol Oncol 1984;18:359-72.  Back to cited text no. 3
    
4.
Eisner RF, Nieberg RK, Berek JS. Synchronous primary neoplasms of the female reproductive tract. Gynecol Oncol 1989;33:335-9.  Back to cited text no. 4
    
5.
Ayhan A, Yalçin OT, Tuncer ZS, Gürgan T, Küçükali T. Synchronous primary malignancies of the female genital tract. Eur J Obstet Gynecol Reprod Biol 1992;45:63-6.  Back to cited text no. 5
    
6.
Eifel P, Hendrickson M, Ross J, Ballon S, Martinez A, Kempson R. Simultaneous presentation of carcinoma involving the ovary and the uterine corpus. Cancer 1982;50:163-70.  Back to cited text no. 6
    
7.
Zaino R, Whitney C, Brady MF, DeGeest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas – A prospective clinicopathologic study of 74 cases: A gynecologic oncology group study. Gynecol Oncol 2001;83:355-62.  Back to cited text no. 7
    
8.
Soliman PT, Slomovitz BM, Broaddus RR, Sun CC, Oh JC, Eifel PJ, et al. Synchronous primary cancers of the endometrium and ovary: A single institution review of 84 cases. Gynecol Oncol 2004;94:456-62.  Back to cited text no. 8
    
9.
Jain M, Puri V. Synchronous carcinosarcoma uterus and primary serous carcinoma of bilateral fallopian tubes: A case report. J Reprod Med 2013;58:361-4.  Back to cited text no. 9
    
10.
Maxwell GL, Chandramouli GV, Dainty L, Litzi TJ, Berchuck A, Barrett JC, et al. Microarray analysis of endometrial carcinomas and mixed mullerian tumors reveals distinct gene expression profiles associated with different histologic types of uterine cancer. Clin Cancer Res 2005;11:4056-66.  Back to cited text no. 10
    
11.
Watanabe M, Shimizu K, Kato H, Imai H, Nakano H, Sugawa M, et al. Carcinosarcoma of the uterus: Immunohistochemical and genetic analysis of clonality of one case. Gynecol Oncol 2001;82:563-7.  Back to cited text no. 11
    


    Figures

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    Tables

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