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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 11  |  Issue : 2  |  Page : 87-90

An unusual occurrence of synchronous gastrointestinal stromal tumor and high-grade serous carcinoma of the endometrium - A rare combination


1 Departments of Pathology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Departments of Surgical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

Date of Submission20-Aug-2020
Date of Acceptance15-Dec-2020
Date of Web Publication25-May-2021

Correspondence Address:
Dr. Daphne Fonseca
Department of Pathology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Road No: 10, Banjara Hills, Hyderabad - 500 034, Telangana
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjmsr.mjmsr_35_20

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  Abstract 


Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract and comprise <2.2% of all GI tumors. The incidence of endometrial cancer in India is 1.2%. Among synchronous cancers, female genital tract tumors, mostly endometrioid/ovarian carcinomas, constitute 5% of GIST patients. We describe an unusual case with synchronous occurrence of GIST of the stomach with high-grade serous carcinoma (HGSC) of the endometrium, which was proven by histopathological examination and further confirmed by immunohistochemistry. This is the first case published so far of a patient with synchronous occurrence of low-risk GIST of the stomach with HGSC of the endometrium. The main objective of the study is to present a unique case because we have not found any reports for coexistence of the described neoplasm as in our patient, and we hope that it will be valuable in future investigations about the genesis, diagnosis, and treatment of these types of tumors.

Keywords: Gastrointestinal stromal tumor, high-grade serous carcinoma of the endometrium, immunohistochemistry, synchronous malignancies


How to cite this article:
Fonseca D, Arya SS, Raju K V. An unusual occurrence of synchronous gastrointestinal stromal tumor and high-grade serous carcinoma of the endometrium - A rare combination. Muller J Med Sci Res 2020;11:87-90

How to cite this URL:
Fonseca D, Arya SS, Raju K V. An unusual occurrence of synchronous gastrointestinal stromal tumor and high-grade serous carcinoma of the endometrium - A rare combination. Muller J Med Sci Res [serial online] 2020 [cited 2021 Jun 23];11:87-90. Available from: https://www.mjmsr.net/text.asp?2020/11/2/87/316694




  Introduction Top


Multiple primary malignancy (MPM) is defined as occurrence of the primary malignancy with different histology to two or more parts of the body that are distinct from each other. These tumors must have definite features of malignancy and the possibility of metastasis must be ruled out.[1],[2] MPM in the same patient when present within 6 months of diagnosis of primary is considered to be synchronous occurrence. When a second malignancy occurs after 6 months of diagnosis or treatment of the primary, then it is metachronous.[3] The incidence of MPM is rare and it has been increased in the last decade. Multiple mechanisms such as hereditary, immune, and environmental factors, e.g., chemical, viruses, and chemotherapeutic regimens, are considered the etiopathogenesis of MPM.[4]

Here, we present a very rare case of synchronous high-grade serous carcinoma (HGSC) of the endometrium and gastrointestinal stromal tumor (GIST) of the stomach.


  Case Report Top


A 56-year-old perimenopausal hypertensive woman with no significant family history presented to the outpatient department with chief complaints of white discharge per vaginum and abdominal discomfort for the past 4 months. On clinical examination, there was a palpable firm lump in the abdomen not extending into pelvis. Radiological investigations were performed. Magnetic resonance imaging of the whole abdomen revealed a lobular altered signal intensity lesion, isointense on T1-weighted (T1W), hyperintense on T2W/STIR sequences with restricted diffusion in the endometrial cavity, measuring 54 mm × 45 mm with focal infiltration of posterior myometrium (>50%) favoring endometrial carcinoma. Further, a well-defined lobular altered signal intensity lesion, isointense on T1W, heterogeneously hyperintense on T2W/STIR sequences with restricted diffusion was noted arising from the distal body of the pancreas, extending into lesser sac, measuring 59 mm × 46 mm, probably metastases. Biochemical examination revealed normal serum CA-125, serum CEA, and serum CA-19-9 levels. Endometrial curetting was sent for histopathological examination (HPE), which showed high-grade endometrial carcinoma. The patient underwent laparoscopic-assisted total abdominal hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic node dissection, para-aortic node sampling, infracolic omentectomy, and multiple peritoneal biopsies with excision of lesser sac mass arising from gastric wall at the posterior upper lesser curvature, and the specimen was sent for detailed HPE.

Grossly, the mass attached to the stomach was globular measuring 7.5 mm × 5.5 mm × 3.5 cm. External surface was smooth and cut surface showed an encapsulated gray-white lobulated cystic mass with hemorrhagic areas. The hysterectomy specimen showed a gray-white friable polypoid mass measuring 6.5 cm × 4.5 cm × 2.5 cm. On HPE, sections from the endometrium showed an infiltrating neoplasm arranged in papillary pattern. The neoplastic cells were pleomorphic showing nuclear pseudostratification, vesicular chromatin, and prominent nucleoli. Tumor involved >50% of myometrial thickness. Sections from the mass attached to lesser curvature of stomach showed a well-encapsulated lesion arranged in lobules with cells in short fascicles and whorls with indistinct cell borders, paranuclear cytoplasmic vacuoles, and moderate cytoplasm exhibiting mild-to-moderate atypia. Focal areas of necrosis, hemorrhage, and microcystic stromal degeneration were noted. Mitosis was 5/5 mm2 and necrosis (5%) was seen. On immunohistochemistry (IHC), the neoplastic cells of the endometrium showed diffuse positivity for p16, null type expression with p53, 30% positivity with ER, and negativity for WT1. The neoplastic cells of the stomach showed positivity with DOG1 and CD117. The above immunoprofile, in correlation with morphologic parameters, confirmed the synchronous occurrence of low-risk GIST of the stomach with HGSC of the endometrium, which has not been documented in the English literature [Figure 1] and [Figure 2].
Figure 1: (a) Gross (endometrium): Gray-white friable polypoid mass measuring 6.5 cm × 4.5 cm × 2.5 cm, (b) Infiltrating neoplasm arranged in papillary pattern, complex branching back to back arrangement of glands (H and E, ×100); inset showing pleomorphic neoplastic exhibiting nuclear pseudostratification with vesicular chromatin and prominent nucleoli (H and E, ×400). (c) p16: Positive, (d) ER: 30% positive, (e) WT1: Negative, (f) p53: Null type

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Figure 2: (a) Gross (gastrointestinal stromal tumor): Encapsulated gray-white lobulated cystic mass with hemorrhagic areas, (b) A well-encapsulated lesion arranged in lobules with cells in short fascicles and whorls (H and E, ×100); inset showing spindle cells with indistinct cell borders, paranuclear cytoplasmic vacuoles and moderate cytoplasm exhibiting mild-to-moderate atypia (H and E, ×400), (c) DOG1: Positive, (d) CD117: Positive

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  Discussion Top


The diagnosis of synchronous malignancies in an individual is rare and difficult. Gluckmann classified second malignancies are occurring in the same individual as synchronous and metachronous. When two malignancies occur simultaneously or within a 6-month period of diagnosis of the first tumor, it is defined as synchronous, and when the second malignancy is diagnosed beyond 6 months' interval, it is diagnosed as metachronous.[3] In the present case, we present simultaneously diagnosed synchronous occurrence of low-risk GIST of the stomach with HGSC of the endometrium. Multiple mechanisms such as hereditary, immune, and environmental factors, e.g., chemical, viruses, and chemotherapeutic regimens, are considered as the pathogenesis of MPM.[4] A tendency of early onset of multiple primary cancers may suggest a genetic association. No genetic or familial risks were reported in the present case on pedigree analysis.

The incidence of endometrial cancer in India is 1.2%.[5] About 1%–2% of women with gynecological cancers are found to have two or more simultaneous independent primary malignancies.[6] Synchronous occurrence of endometrial and ovarian malignancies constitutes 50%–75% female genital tract malignancies.[6] Rarer combinations of synchronous tumors are less well studied, which may represent either unusual patterns of metastasis or multifocal origin, each deserving treatment on its own merit.[6]

GIST is the most common mesenchymal tumor of gastrointestinal tract (GIT)[7] and accounts for 2.2% of GIT malignancies,[8] with an incidence of 10–20 per million.[9] Stomach (60%–70%) is the most frequent site of GIST followed by small intestine, colon and rectum, and esophagus.[10] It is reported that the most common synchronous malignancy is gastrointestinal carcinoma, which is mainly located in the stomach (47%).[11] The incidence of GIST as a synchronous malignancy was 2.95%–33% as reported in previous studies.[11] Agaimy et al., in their meta-analysis, demonstrated that 9.2% of GIST patients suffered second primary carcinoma.[11] Among these synchronous cancers, female genital tract tumors constituted 5% (25/4813) of GIST patients.[11]

GISTs are mostly considered nonhereditary or sporadic. Murphy et al., in their study on association between GIST and other additional cancers have found a standardized incidence ratio of 1.96 in uterine adenocarcinomas.[12]

The preoperative diagnosis of synchronous GIST with other malignancies is particularly difficult, and only 12.5% (4/32) of patients are preoperatively diagnosed with concurrent digestive tract carcinomas.[13] In our case, a preoperative diagnosis of GIST was not made. A previous study indicated that the majority of synchronous GISTs with other malignancies expressed CD117 and CD34.[11] Lin et al. reported that synchronous gastric GIST presented a lower expression rate of CD117 and CD34.[14] In the present case, the diagnosis of GIST was confirmed with immunohistochemical expression of CD117 and DOG1. Hence, interpretation of IHC in case of synchronous GIST remains crucial.

In one of the largest series on synchronous second tumors with GIST by Rodriquenz et al., they have proposed KIT exon 9, 11 and heterozygous mutations in patients who developed female genital tract tumor, but the sample was too small to have a clinical relevance and no definitive conclusion was drawn due to the lack of molecular analysis in second tumors.[15]

It is reported that the 5-year overall survival rate of gastric low-risk GIST patients with synchronous gastric cancer was significantly lower than that of gastric low-risk GIST patients without synchronous gastric cancer. The prognosis of our patient is uncertain as there is no previous literature available on synchronous occurrence of gastric low-risk GIST and high-grade endometrial cancer.[14] Over 15 weeks now, our patient's follow-up remains uneventful.


  Conclusion Top


This case report details a rare synchronous occurrence of gastric low-risk GIST of the stomach and HGSC of the endometrium, the prognosis of which is currently unknown. Further studies are required to clarify the molecular and genetic mechanisms of carcinogenesis and progression associating GIST and synchronous tumors. The registry of such patients with second malignancies may provide useful information about the genetic link between the two malignancies and help in furthering clinical research.

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.
Aydiner A, Karadeniz A, Uygun K, Tas S, Tas F, Disci R, et al. Multiple primary neoplasms at a single institution: Differences between synchronous and metachronous neoplasms. Am J Clin Oncol 2000;23:364-70.  Back to cited text no. 1
    
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Derwinger K, Gustavsson B. A study of aspects on gender and prognosis in synchronous colorectal cancer. Clin Med Insights Oncol 2011;5:259-64.  Back to cited text no. 2
    
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Fonseca D, Musthyala B, Ahmed F, Murthy SS, Raju KV. A tale of synchronous lung carcinoma and diffuse large B-cell lymphoma of ileum: A rare combination. Lung India 2015;32:398-401.  Back to cited text no. 3
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Sakellakis M, Peroukides S, Iconomou G, Boumpoucheropoulos S, Kalofonos H. Multiple primary malignancies: A report of two cases. Chin J Cancer Res 2014;26:215-8.  Back to cited text no. 4
    
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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 5
    
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Singh N. Synchronous tumours of the female genital tract. Histopathology 2010;56:277-85.  Back to cited text no. 6
    
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Feng F, Liu Z, Zhang X, Guo M, Xu G, Ren G, et al. Comparison of endoscopic and open resection for small gastric gastrointestinal stromal tumor. Transl Oncol 2015;8:504-8.  Back to cited text no. 7
    
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Sheppard K, Kinross KM, Solomon B, Pearson RB, Phillips WA. Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit Rev Oncog 2012;17:69-95.  Back to cited text no. 8
    
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Tzen CY, Wang JH, Huang YJ, Wang MN, Lin PC, Lai GL, et al. Incidence of gastrointestinal stromal tumor: A retrospective study based on immunohistochemical and mutational analyses. Dig Dis Sci 2007;52:792-7.  Back to cited text no. 9
    
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Zhao X, Yue C. Gastrointestinal stromal tumor. J Gastrointest Oncol 2012;3:189-208.  Back to cited text no. 10
    
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Agaimy A, Wünsch PH, Sobin LH, Lasota J, Miettinen M. Occurrence of other malignancies in patients with gastrointestinal stromal tumors. Semin Diagn Pathol 2006;23:120-9.  Back to cited text no. 11
    
12.
Murphy JD, Ma GL, Baumgartner JM, Madlensky L, Burgoyne AM, Tang CM, et al. Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study. Cancer 2015;121:2960-7.  Back to cited text no. 12
    
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Zhang P, Deng R, Xia Z, Shuai X, Chang W, Gao J, et al. Concurrent gastrointestinal stromal tumor and digestive tract carcinoma: A single institution experience in China. Int J Clin Exp Med 2015;8:21372-8.  Back to cited text no. 13
    
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Lin M, Lin JX, Huang CM, Zheng CH, Li P, Xie JW, et al. Prognostic analysis of gastric gastrointestinal stromal tumor with synchronous gastric cancer. World J Surg Oncol 2014;12:25.  Back to cited text no. 14
    
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Rodriquenz MG, Rossi S, Ricci R, Martini M, Larocca M, Dipasquale A, et al. Gastrointestinal stromal tumors (GISTs) and second malignancies: A novel “sentinel tumor”? A monoinstitutional, STROBE-compliant observational analysis. Medicine (Baltimore) 2016;95:e4718.  Back to cited text no. 15
    


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