Synchronous occurrence of primary breast cancer and renal cell carcinoma: A case report and literature review

Abstract

Introduction and importance

Multiple Primary Malignant Neoplasms (MPMNs) are rare and refer to the occurrence of two or more distinct primary cancers with unrelated histopathological features in one patient. MPMNs can be classified as synchronous when tumors appear simultaneously or within six months of each other, and as metachronous when identified six months or more after the initial cancer diagnosis. While breast cancer often co-occurs with other primary cancers such as colorectal, endometrial, and ovarian cancers, the simultaneous presence of invasive lobular breast carcinoma and clear cell renal cancer is rare.

Case presentation

Here, we present the case of a 59-year-old postmenopausal woman who initially presented with breast carcinoma. Further investigation revealed a mass in the left kidney. The patient underwent a radical mastectomy and axillary dissection, followed by a left nephrectomy. After 8 months follow up, the patient is doing well and disease-free.

Clinical discussion

Based on our case and literature review, the co-occurrence of breast carcinoma with renal cell carcinoma (RCC) is uncommon. Most reported cases involve metastatic tumors or metachronous breast malignancy with RCC. The etiology of synchronous malignancy is complex, and treatment options usually include a combination of surgery and/or adjuvant therapy.

Conclusion

This case report contributes valuable insights to the limited literature on synchronous breast cancer with renal cell carcinoma. The rarity of this simultaneous occurrence underscores the importance of considering such cases. Documenting these cases is crucial for increasing awareness and reducing the resulting morbidity and mortality.

Highlights

• •Multiple primary malignant neoplasms (MPMNs) are rare.
• •Synchronous tumors are defined as two tumors arising concurrently or within six months of each other.
• •Multiple synchronous malignancies are rarer than metachronous ones.
• •Breast cancer is the most common tumor to be associated with other primaries.
• •The synchronous occurrence of breast and renal cell carcinoma is uncommon.

1. Introduction

Primary malignancies of different organs can occur in the same patient. “Multiple Primary Malignant Neoplasms” (MPMNs) is the term used to describe the detection of two or more distinct primary cancers with unrelated histopathological features in one patient. The term “MPMNs” was initially introduced by Billroth in 1889 and later formally defined by Warren Gates in 1932 [1]. MPMNs are classified as synchronous (SMPMN) when two tumors appear at the same time or when the second tumor develops within six months of the initial diagnosis [2]. On the other hand, metachronous cancers (MMPMN) are those that are identified six months or more after the initial cancer diagnosis [2]. The primary cause of multiple primary malignant tumors remains largely unknown. However, it is believed that certain factors, such as immunological, environmental, and hereditary elements, may play a role in the development of multiple cancers [3,4]. Breast cancer is frequently observed to co-occur with other primary cancers, especially colorectal, endometrial, and ovarian cancers [5]. However, the occurrence of invasive lobular carcinoma with clear cell renal cancer is relatively rare [5].

In this case report based on SCARE 2023 guidelines for better reporting [6], we report a rare case of synchronous invasive lobular breast carcinoma and renal clear cell carcinoma in a 59-year-old female.

2. Case presentation

A 59-year-old postmenopausal woman, non-smoker, non-alcoholic, with no family history of malignancy and with well-controlled hypertension, presented with a palpable mass in her left breast. The mass has been slowly increasing in size over the last 3 months. The patient had a good functional status (ECOG-0). On the physical examination, there was a mass approximately 3 cm in diameter in the upper outer quadrant of the left breast. There was no nipple discharge or axillary mass. The patient had no systemic complaints. The opposite breast and axilla were normal. The systemic examination was normal.

A left radical mastectomy and axillary dissection was done by a surgeon at a peripheral hospital. The histopathological examination of breast revealed infiltrating carcinoma. On microscopy, it was an infiltrating lobular carcinoma grade II SBR (Fig. 1). Mitotic activity was seen. No evidence of haemorrhage or necrosis. There were no lymphovascular emboli or perineural invasion. 12 nodes were dissected, none were metastatic. All the margins and the rest of the breast were free of tumor. Breast carcinoma was of stage pT2N0. On immunohistochemistry (Fig. 2), the tumor was reactive for both estrogen and progesterone receptors and negative for HER2 protein overexpression. Finally, the Ki67 proliferation index was 15 %.

Fig. 1.

Postoperative histopathological analysis H&E staining revealed an infiltrating lobular carcinoma grade II SBR.

Fig. 2.

Immunohistochemistry of the infiltrating lobular carcinoma A) ER receptors +ve B) PR receptors +ve C) HER2 −ve.

The patient was referred to our hospital for further management. Computed tomography scan of brain, chest, abdomen and pelvis for metastatic workup was done and showed Lower pole renal lesion measuring 8 × 7 × 5.5 cm, hypervascular, with features suggestive of primary malignancy (Fig. 3).

Fig. 3.

Axial view abdomen computed tomography scan showing a Lower pole renal lesion measuring 8 × 7 × 5.5 cm, hypervascular, with features suggestive of primary malignancy.

The case was discussed in our multidisciplinary tumor (MDT) board meeting, and the consensus of the board was to do a left nephrectomy. The histopathological examination of renal specimen revealed a largely hemorrhagic tumor measuring 6.0/6.0 cm. Microscopy showed clear-cell renal carcinoma confined to kidney (Fig. 4). The tumor was well encapsulated with wide areas of haemorrhage and necrosis. There was no invasion into the capsule nor perinephric fat. All the margins were free. Renal carcinoma was of stage pT1bN0 Fuhrman grade II. The postoperative course went smoothly.

Fig. 4.

Postoperative histopathological analysis H&E staining revealed a low-grade renal cell carcinoma (clear cell type, Fuhrman grade 2).

A PET scan was requested to rule out the presence of other tumoral lesions, and it revealed the absence of any suspicious lesions.

The Patient was finally diagnosed as a case of synchronous carcinoma of left breast (pT2N0M0) along with renal cell carcinoma in the left kidney (pT1bN0M0, Grade II). She received adjuvant endocrinotherapy with aromatase inhibitor letrozol for the breast cancer and was advised close follow-up for renal carcinoma. To date (8 months post-operative), there is no recurrence or metastases have been identified. She is asymptomatic and leading a good quality of life.

3. Discussion

Multiple primary tumors may occur within the same patient. The existence of two or more separate primary cancers in one patient, was first described by Billroth in 1889 [7]. Subsequently, MPMTs were reported in a detailed study by Warren and Gates in 1932 [8]. Warren and Gates established specific criteria which should be fulfilled before declaring multiple co-occurring neoplasia to be MPMTs. Firstly, both tumors must present malignancy differing pathologically from each other. Secondly, the possibility of metastasis should be ruled out. Thirdly, clear features of malignant transformation should be present on histologic examination [9]. Our case fully satisfies these criteria.

The classification of a second primary tumor is determined as either synchronous or metachronous, depending on the time interval between the discoveries of the distinct neoplasms [10]. Synchronous cancer is defined as two or more neoplasms discovered in the same patient at the same time. The Surveillance Epidemiology and End Results (SEER) project [11] gave a different definition: synchronous multiple tumors are when two or more primary cancers are diagnosed within two months of each other. Conversely, the International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC) define synchronous multiple primary malignancies as the presence of two or more primary malignancies diagnosed within a period of six months [12,13]. Our case is synchronous because both tumors were incidentally diagnosed simultaneously during our patient's clinical presentation.

Multiple primary malignancies occur extremely rarely. They can occur in either the same or different organ systems, with prevalence ranging from 2 % to 17 % [14]. Metachronous malignancies have a higher prevalence compared to synchronous malignancies [15].

The global rise in the incidence of multiple primary malignancies is a significant challenge. Understanding the characteristics of metachronous and synchronous MPMTs can help improve treatment approaches for patients. The etiology of this entity remains incompletely understood. Researchers have explored several epidemiological factors to investigate the etiology of multiple primary tumors.

The exact pathophysiology for MPM remains incompletely comprehended and remain a subject of ongoing discussion. Possible contributing factors include factors include environmental factors such as alcohol, tobacco, exposure to ultraviolet light, various types of pollution, certain occupational duties that involve exposure to carcinogenic compounds, genetic predisposition, chemotherapy, radiation exposure, hormonal dysregulations, and gender-specific elements [16]. None of these risk factors were present in our case.

Multiple primary malignancies can occur at any age. However, previous research suggests that individuals diagnosed with multiple primary malignancies generally have an older age profile compared to those with a single primary cancer. Several investigations have shown that more than 75% of patients identified with MPMTs were 50 years old or older [[17], [18], [19]].

In terms of gender distribution it is observed that males have a higher incidence rate than females in both synchronous and metachronous neoplastic incidents [20,21].

Previous research has documented the coexistence of breast cancer with synchronous tumors in other organs [22]. Additionally, there have been associations found between renal cell carcinoma (RCC) and other types of tumors [23]. However, the occurrence of both RCC and breast cancer together is exceptionally rare in the literature. Nonetheless, a retrospective analysis of 72 patients was conducted by Jiao et al. revealed 16 cases (22.2 %) of primary malignant tumors, out of which 8 had both breast and renal cancer [24]. In our case, the renal tumor was fortuitously detected during the metastatic workup of the breast lesion. The patient did not exhibit any noticeable clinical symptoms of a renal tumor that would prompt them to seek medical counsel.

Estrogens are suggested to play a role in renal cell carcinoma (RCC) that is related with other primary tumors affecting tissues targeted by steroid hormones, such as the breast, endometrial, and ovary [25]. According to a study, by Banerjee et al. it was found that estradiol can stimulate the development of micronuclei and aneuploidy in hamster renal tissues [26]. Estrogens have the potential to enhance tumor development through many mechanisms; a) It has the potential to function as carcinogens, which can create direct covalent linkage to DNA, b) it has the potential to act as promoters of other carcinogens, c)it may have a permissive influence on growth factors [25]. Receptors for estrogen and progesterone have been proven to exist in cases of human RCC [25].

Primary breast cancer is the most prevalent type of tumor that is linked to multiple other primary tumors [27]. Women diagnosed with breast cancer had a 17 % increased risk of developing a second primary malignancy, according to a meta-analysis [22]. This increased risk often leads to the occurrence of malignancies in organs including the liver, head, and neck of the female genital tract, as well as the opposite breast [23].

According to the literature, Renal cell carcinoma has been associated to other primary malignancies, such as those of the colon [28], rectum [28], stomach [29], prostate [28], bladder [28], endometrium [30], ovary [30], breast [28], nasopharynx [29], lung [31], and haematological malignancies.

Finding secondary primary malignancies is often an unexpected discovery while conducting preoperative screening for distant metastases. This raises a challenge regarding whether the therapy should be administered at separate times or concurrently, and if at separate times, which tumor should be prioritized [32]. The study conducted by Lee et al. found that performing two separate neoplastic regional excisions produced superior outcomes compared to wide and extensive excision [33]. The occurrence of breast and renal cancer simultaneously is extremely uncommon in the literature, and there is a lack of sufficient evidence to establish a definitive consensus on the best approach for planning the order of treatment in such situations. In our case, it was thought that breast cancer might have been the more aggressive tumor and was given treatment priority. The postoperative histopathologic staging of both tumors revealed T2N0M0 breast cancer (stage 1A), and T1bN0M0 (Stage 1) renal cancer. The postoperative period was uneventful. Eight months follow-up presented no signs of recurrence and no metastasis in the tumors.

To prevent the recurrence of renal cell carcinoma, it is recommended to have regular tests such as urine analysis, general examination, palpation of lymph nodes every two years, and cystoscopy every ten years [34].

Fuhrman proposed a reliable grading method for predicting the 5-year survival rates of RCC, providing valuable prognostic predictions. It is unrelated to the stage of the tumor. The statistics are as follows: 89 % for Grade 1, 65 % for Grade 2, and 46 % for the Grades 3 to 4 [35]. Our patient falls into the 65 % category as their renal cell carcinoma (RCC) has been classified as Grade 2 according to Fuhrman's classification.

According to a study conducted by Sato et al., the presence of additional primary lesions at the time of nephrectomy for RCC was found to be an independent predictor of overall survival after the procedure. Moreover, it has been observed that patients diagnosed with localized cell carcinoma (RCC) and coexisting malignancy tend to have a lower overall survival rate compared to patients with localized RCC alone [36].

4. Conclusion

In conclusion, Multiple primary malignancies are becoming more common due to improved screening methods and increased patient awareness. This highlights the need for a comprehensive approach to understanding and managing these complex cases. Studying synchronous malignancies provides evidence for clinical evaluation, future treatments, and insights into cancer's underlying causes and development processes. Genetic and molecular profiling research holds potential for understanding these tumors and developing more effective treatment modalities.

Consent to participate

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

Ethical approval has been exempted by our institution.

Funding

No funding was received for this case report.

Author contribution

Fatima Rezzoug: Writing, review and editing of the manuscript.

Ikram Kharmach: have helped writing the article, data collection.

Jihan Derfoufi: have helped collecting data.

Ouissam Al Jarroudi: supervised the writing of manuscript.

Sami Aziz Brahmi: supervised the writing of manuscript.

Said Afqir: supervision and data validation.

Guarantor

Rezzoug Fatima.

Declaration of competing interest

The authors have no conflict of interest to declare.