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Quadruple metachronous primary cancer in a single patient: A rare case report

1 Department of Radiation Oncology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India
2 Department of Pathology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India

Date of Submission11-Jul-2019
Date of Acceptance02-Dec-2019
Date of Web Publication26-Nov-2020

Correspondence Address:
Virendra Bhandari,
Department of Radiation Oncology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_484_19

 > Abstract 

Multiple primary cancer is a condition where multiple occurrences of different malignancies occur in the same individual. As there is a rise in the long-term survival of patients, multiple primary cancer is now not a rare entity. To see four different tumors in the same patient is very rare, and here, we report the case of a 60-year-old female patient with quadruple primary cancer of bilateral breast, esophagus, and sarcoma of the leg.

Keywords: Different histology, metachronous primary, quadruple cancer

How to cite this URL:
Ali T, Khan A, Kathed V, Verma S, Sarolkar A, Bhandari V. Quadruple metachronous primary cancer in a single patient: A rare case report. J Can Res Ther [Epub ahead of print] [cited 2022 Jun 25]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=300999

 > Introduction Top

Multiple primary cancer is a condition where more than two or more cancers which develop independently with no relation to each other. Warren and Gates[1] suggested three diagnostic criteria for multiple primary cancers that each cancer must be definitively malignant, must be histopathologically different, and the possibility of metastasis among the cancers must be excluded. The incidence of quadruple primary cancer has been reported <0.1% in the literature. Ayhan et al.[2] reported that the incidence of multiple primary cancer of the female reproductive tract is 1.7%, and 51.7% of these occur in the endometrium and ovary because of the same causative agent.

We report here a rare entity of quadruple primary cancer involving esophagus and leiomyosarcoma of the leg, which occurred after both breast cancers.

 > Case Report Top

A 60-year-old female presented to us with a history of treatment for infiltrating duct carcinoma left breast with surgery followed by chemotherapy and radiotherapy in 1996. Her disease was controlled for 2 years and then, she developed a lump in the upper-outer quadrant of the right breast in 1998 for which right modified radical mastectomy was done, histopathology was infiltrating duct carcinoma. She received four cycles of chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil. She did not receive radiotherapy but was started on tamoxifen 20 mg daily, which she continued for 8 years.

She presented to us in 2014 with complaints of difficulty in swallowing for solids for 2 months. There was no history of hematemesis or pain during swallowing. Gastroduodenoscopy showed large proliferative growth 3 cm below the cricopharynx, the scope was not negotiable beyond. Histopathology was squamous cell carcinoma-Grade II [Figure 1]. Whole-body positron-emission tomography-computed tomography (PET-CT) was suggestive of focal abnormal increased fluorodeoxyglucose (FDG) uptake in the upper third of the thoracic esophagus, measuring 3.6 cm in length and 1.5 cm in thickness (SUV ma × 5.6). No focal abnormal increased FDG uptake was noted in hepatic parenchyma and visualized bones. She was given concurrent chemotherapy with weekly cisplatin and radiotherapy using intensity-modulated radiotherapy with daily imaging (60 Gray/30 fractions) in May 2014. The patient tolerated the treatment well and started taking solid diet. Posttreatment PET-CT scan and the upper gastrointestinal scopy showed no evidence of disease.
Figure 1: Histopathology of lesion in the esophagus (squamous cell carcinoma)

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During follow-up in May 2019, the patient developed swelling in the left mid-calf 12 cm × 10 cm, which was well-defined, bosselated, and mobile. There were no inguinal or popliteal lymph nodes palpable. Magnetic resonance imaging of the left leg showed mixed intensity lobulated dumbbell-shaped solid mass lesion with predominant exophytic component noted in the subcutaneous tissue overlying the anteromedial aspect of the left mid-calf measuring 6.5 cm × 5.7 cm × 9.2 cm with no evidence of infiltration into the underlying muscle, bones, nerves, or vessels. Multiple adjacent satellite lesions were also seen. The lesion was hyperintense on T2 and hypointense on T1. The patient underwent wide local excision of the mass, and histopathology was suggestive of spindle cell sarcoma [Figure 2]. Immunohistochemistry revealed that tumor was positive for S-100, smooth muscle actin, DESMIN, and Ki-67 which was suggestive of leiomyosarcoma. At present, she on postoperative local radiotherapy.
Figure 2: Histopathology of leiomyosarcoma

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 > Discussion Top

Multiple primary cancer is an entity of two or more cancers that are not related directly and develop independently. Billroth[3] had first reported case of tumors in multiple organs in 1889, since then, the occurrence of multiple primary cancer has risen as the cure rate, and survival rate of such patients have dramatically increased due to improvements in diagnostic techniques and treatment facilities.

As per Moertel,[4] multiple primary cancers observed at the same time or within 6 months are synchronous, and cancers developing with more than 6 months intervals are metachronous. It is difficult to differentiate between multiple primary and multicentric tumors with these criteria, and therefore, Moertel[4] also suggested a classification, including multiple primary and multicentric cancers, and this classification is widely used today. Group I includes multiple primary cancer occurring in organs with the same histology. Group I is subdivided into Group IA, including cancers that occur in the same tissue and organ, Group IB, including cancers that are from the same tissue and different organs, and Group IC, including cancers that occur in bilateral organs (i.e., breast, ovary, etc.). Group II includes multiple primary cancers originating from different tissues, and Group III consists of cancers from different tissues and organs that concurrently exist with Group I, forming multiple primary cancers. Our patient comes in Group III as it has arisen from different tissues and has different histology which are rare to occur.

The etiology of these types of cancers is not fully understood, but many theories have been suggested, such as field cancerization, genetic cause, radiation, and chemotherapy for primary cancer, prolonged exposure to carcinogens, and family history of cancer. Slaughter et al.[5] suggested that field cancerization is a condition in which when the body is exposed to carcinogens, other organs besides the organ with cancer are also exposed to the carcinogen and carry a high risk of cancer.

There are no fixed treatment guidelines to be followed for patients with multiple primary cancers. However, if the aim is curative, radical therapy is indicated. If radical therapy of primary cancer is not possible, conservative, and palliative therapy can be considered. Another theory suggests that cancers developing in other sites originate from the histologically similar epithelium.[6]

Noh[7] reported a patient with breast cancer at the age of 45 years, rectal cancer at the age of 63 years, and ovarian cancer and endometrial cancer synchronously at the age of 68 years. Although none of her family members had breast or ovarian cancer.

In our patient, all the primaries occurred at an interval of more than 6 months with different tissue of origin and different histologies making it metachronous type of multiple primary cancer.

 > Conclusion Top

Multiple primary cancer is quite rare in India. Due to the better treatment facilities and treatment with increasing long-term survival, the incidence is rising. The prevention of such an entity is a new challenge that has to be faced.

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.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Warren S, Gates O. Multiple primary malignant tumors; surgery of literature and statistical study. Am J Cancer 1932;16:1358-414.  Back to cited text no. 1
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. 2
Billroth T. General Surgical Pathology and Therapeutics in 51 Vorlesungen: A Textbook for Students and Physicians in Fifty-One Lectures. 14th ed. Berlin, DE: G. Rerimer; 1889.  Back to cited text no. 3
Moertel CG. Multiple primary malignant neoplasms: Historical perspectives. Cancer 1977;40:1786-92.  Back to cited text no. 4
Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953;6:963-8.  Back to cited text no. 5
Lauchlan SC. Conceptual unity of the Müllerian tumor group. A histologic study. Cancer 1968;22:601-10.  Back to cited text no. 6
Noh SK, Yoon JY, Ryoo UN, Choi CH, Sung CO, Kim TJ, et al. A case report of quadruple cancer in a single patient including the breast, rectum, ovary, and endometrium. J Gynecol Oncol 2008;19:265-9.  Back to cited text no. 7


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