A Case Report of Double Primer Cancer: Malignant Phyllodes Tumor and Invasive Ductal Carcinoma
Lauraine Wijayaningtyas Sinuraya
1, Kristanto Yuli Yarso
2*1 Department of Surgery, Resident of General Surgeon, Universitas Sebelas Maret, Surakarta, Indonesia
2 Department of Surgery, Oncology Surgeon, Universitas Sebelas Maret, Surakarta, Indonesia
*Corresponding author:
Kristanto Yuli Yarso
Department of Surgery, Oncology Surgeon, Universitas Sebelas Maret, Surakarta, Indonesia
INTRODUCTION
In some cases, multiple primary malignancies are common, and the number has been increasing due to improvements in diagnostic technology [1]. Nevertheless, multiple primary malignancies have happened in multiple organs. Billroth described this phenomenon at the end of the nineteenth century, and several cases of double or triple primary malignancies have been reported since then [2]. Epidemiological studies have shown the frequency of some area codes in the range of 2–17%
[3]. The interval between those tumors diagnosed divides into two categories that are synchronous malignancy and metachronous malignancy. Secondary tumors that appeared at the same time as or within six months of the first malignancy were referred to as synchronous malignancies, and secondary tumors that occurred more than six months after the first malignancy were referred to as metachronous malignancies [1].
The most common area of primary tumors is in the head and neck (34.15%), followed by gynecologic cancer (21.95%), breast (17.07%), lung cancer (14.9%), esophageal cancer (7.3%), and then other tumors (14.6%). Of the secondary malignancies, breast cancer (21.95%) and gastrointestinal tract (21.95%) are the most common, and lung cancer (17.07%) and gynecologic cancer (12.20%) followed [1]. One case of double primary cancer is often found in melanoma. Patients with cutaneous melanoma (CM) include primary- secondary malignancies, especially secondary primary melanoma, lymphoma, and various other cancers (breast, thyroid, or prostate). It has been reported that the risk is high [4].
Multiple primaries have been reported in patients with breast cancer in the range of 4.1% to 16.4%. The median time from the first malignancy to the second malignancy was five to eight years [3]. Many risk factors have been identified, including early onset menstruation, late menopause, childbirth, and family history. First- A R T I C L E I N F O
Received : 06 May 2022 Reviewed : 06 June 2022 Accepted : 26 July 2022 Keywords:
breast cancer, double primer cancer, invasive ductal carcinoma, malignant phylloides tumor
A B S T R A C T
Introduction: Multiple primaries have been reported in patients with breast cancer in the range of 4.1% to 16.4%. This report followed the standard Surgical Case Report (SCARE) and discussed two histologically distinct breast cancer malignancies. This paper also explored the risk factor, pathogenesis, treatment, and prognosis of multiple primary malignancies in the same organs, especially in the breasts.
Case Presentation: The patient was a 45-year-old woman with a lump in the left and right breasts for five years. The patient claimed that the lump was enlarged and painless. The tumor size of the left breast was 3 x 2 x 3 cm, the right breast was 4 x 2 x 4 cm, and the patient had no enlargement of lymph nodes. The patient underwent a biopsy examination of the left breast showing invasive ductal carcinoma NST (No Special Type) 3rd grade with LV1 (+). The biopsy examination of the right breast showed malignant phyllodes tumor. Thus, the patient must undergo chemotherapy and mastectomy as definitive therapy. The patient has already completed the treatment and is currently under evaluation.
Conclusion: This report looked for the rare case of double primary malignancies in the breasts.
It highlighted double primary cancers starting to increase these days but in a particular way because it happens in the same organ, the breasts. However, medical literature rarely presented a synchronous malignancy case, prompting the publishing of this case. With improved cancer treatment and more prolonged survival, the number of patients with double cancers is increasing.
degree relatives are about twice as likely to develop the disease. Many highly permeable breast cancer susceptibility genes include BRCA1 and BRCA2. These genes increase the risk of breast and ovarian cancer.
P53 (Li Fraumeni Syndrome) and PTEN (Cowden Syndrome), two genes linked to rare cancer syndromes, have also been linked to an increased risk of breast cancer [5]. For the breast, the percentage of a double primary is 10% [6]. This study presents a case of a double primary tumor that occurred in the same organ and is the synchronous malignancy that rarely happens these days.
CASE PRESENTATION
The patient was a 45-year-old woman with a breast lump in the right breast near the armpit in the last five years. The initial size of the lump was about a grape size, painful, and enlarged slowly. At the end of 2020, a lump appeared on the left breast around 12 o’clock. The left lump widened faster, with an initial size as big as a corn seed and grown as big as a ping pong ball. The patient claimed no history of pregnancy during her 18 years of marriage. Also, the patient used no hormonal contraception and had no history of breast cancer in her family. The patient had regular monthly menstruation but always be accompanied by pain in the breast, starting from two weeks before until the end of menstruation.
Physical examination found asymmetrical breasts, right and left breast mass, left lump size 3 x 2 x 3 cm, right lump size 4 x 2 x 4 cm, non-mobile consistency, and not-clear boundaries. The patient had no enlargement of lymph nodes. Sores, nipple retraction, and peau d’orange appearance were denied.
The patient did a mammary ultrasound examination at Indriati Hospital in February 2021 (Figure 1). On the right mammary examination, the lesion appeared solid, multiple, lobulated, and conglomerated with an irregular border. The lesion was located around 9 o’clock with a size ± 4.34 x 2.23 x 4.08 cm (Birads 4A). On the left mammary examination, the lesion appeared solid and immobile, with an irregular border and regular contours.
The lesion was located at the upper outer of the left mammary with a size ± 2.82 x 2.12 x 2.96 cm (Birads 4C). Thus, from the ultrasound examination, the patient decided to pursue a biopsy of the mentioned lesion.
The patient underwent a right mammary biopsy at Indriati Hospital on February 2021. On the microscopic view, the lesion showed mesenchymal tumor tissue composed of spindle cells, infiltrative, atypical cells, and pleomorphic with round, oval, and spindle with binucleated and multinucleated, coarse chromatin and myxoid stroma between the swollen connective tissues and glands with partially differentiated rhabdoid cells (Figure 2). Macroscopic examination showed one piece
of tissue with I-IV thread markings measuring 6.5 x 5 x 2 cm, white color, supple. Cleavage obtained a mass size of 2.5x2x5.5 cm. The examination concluded that the patient had a malignant phyllodes tumor with Rhabdoid differentiated on the right mammary (Figure 3).
The patient’s cancer stage was T2N0.
Figure 1. Ultrasound Examination at Indriati Hospital on February 2021. (A) Right breast; (B) Left breast
A B
Figure 2. (A) Histopathology slide of infiltrative ductal carcinoma; (B) Histopathology of malignant phyllodes.
A B
Figure 3. (A) Right Mammary Biopsy at Indriati Hospital in February 2021; (B) Left Mammary Biopsy at Indriati Hospital in March 2021
Figure 4. Clinical appearance after undergoing mastectomy surgery on both breasts
suppressor genes. It acts as an inhibitor of the PI3K/
AKT/mTOR signaling pathways that control angiogenesis and cell proliferation [11]. Mutations of PTEN are related to an elevated risk of malignant and benign tumors [12]. Loss of PTEN activity increases the phosphorylation of various cellular proteins, affecting growth, migration, and apoptosis ]13]. To diagnose the mutations of PTEN, DNA was extracted from peripheral blood leukocyte samples. Germline variants were assessed in PTEN exons (along with the intron-exon boundary) by PCR and sequencing [14].
Epithelial cadherin (CDH1) is a member of classical cadherin (the others are Neural cadherin (N-cadherin) and Vascular Endothelial cadherin (VE-cadherin)). These single-pass transmembrane glycoproteins are found in many tissues and play a role in Ca2+- dependent intercellular adhesion [15]. Immunohistochemical staining is used to diagnose [16]. Understanding how cadherin affects cell behavior can help regulate cadherin activity and design potential therapeutic interventions to prevent tumor cell growth, infiltration, and metastasis. The therapeutic target may be epigenetic E-cadherin activation or N-cadherin inactivation. In diverse types of cancer, increased infiltration is associated with the downregulation of the gene encoding E-cadherin (CDH1).
The CDH1 promoter is hypermethylated in human breast cancer, hepatocellular carcinoma, and prostate cancer.
Decreased DNA methylation in mouse models of colorectal tumors has been reported to result in inhibition of tumor growth. Therefore, it may be a new target for cancer treatment. For example, thymine DNA glycosylase (TDG) directly targets specific sequences of DNA, causing local DNA demethylation at key regulatory sequences and enhancing gene induction. Another idea is to target the intramembrane proteases of the rhombic family RHBDL2 to regulate the migration of cancer cells by E-cadherin functional inactivation [17].
The pathophysiology of multiple primary malignancies has been proposed as a combination of common- carcinogen-induced multiple cancers in an exposed epithelial surface, known as “field-cancerization,” and a genetic predisposition to neoplasia [6]. A combination of some factors contributes to multiple cancers in most patients. Genetic predisposition for double primary breast cancer can be seen with germline mutation BRCA1/2 and possibly other mutations. After ten years of breast cancer diagnosis, 30% of patients with this mutation would be diagnosed with contralateral breast cancer [18].
In common, malignant phyllodes growth are one- sided and unifocal. However, some may be as reciprocal and multifocal lesions. Histologically, malignant phyllodes neoplasm is biphasic fibroepithelial tumors comprising the tissue and stromal parts. The epithelial ducts are organized into crevices and cystic structures surrounded by a leaf-shaped stroma. The stromal component shows different histological manifestations. In general, the The patient received three chemotherapy cycles with
paclitaxel and epirubicin since April 9, 2021, along with mastectomy surgery of the left breast in June 2021. In addition, the patient received another three cycles of chemotherapy with the same antineoplastic agents and completed on August 13, 2021, followed by mastectomy surgery of the right breast in September 2021.
Definitive treatment was done to the patient, and currently, she is under evaluation post-surgery. So far, for nine months postoperatively, the patient has not felt any significant complaints and has not complained of any residing lumps on both breasts (Figure 4).
DISCUSSION
This report tells cases of patients with two histologically distinct malignancies. Since some patients had no family history of malignant tumors, the researchers were urged to consider the presence of inherent and extrinsic risk factors that could explain the sporadic occurrence of double primary cancer. The most important hazard factors for double primary cancer are tobacco, alcohol, or radiation exposure. The second primary breast cancer can be synchronous or metachronous in the contralateral breast. Most are metachronous. Meta synchronous breast cancer accounts for 5% to 6% of cancer cases and about 1% to 2% of women with breast cancer [7].
Breast cancer patients have been reported to have multiple primary tumor incidence rates ranging from 4.1% to 16.4%. The median time for secondary malignancies was between five and eight years, but this case shows that the secondary malignancy happened almost simultaneously. Double primary cancer is a synchronous category rarely reported in the literature.
Reproductive or hormonal and hereditary variables (e.g., BRCA1, BRCA2) and corpulence are common chance variables for double primaries [3]. One study revealed that the prevalence of primary doubles varied from 1%
in the initial liver primary to 16% in the initial bladder primary. In the case of breasts, the percentage of double primary is 10% [7].
The breast is one of the anatomical sites of most cancers classified because of the world-main threatful neoplasm and nonetheless disadvantageous for some of the damaging effects of desperation in a woman [8].
The pathway of breast malignant neoplastic disease is multidimensional and inefficaciously learned; however, the bound disposal of a variable is known. Advancing age and female gender are the most common predisposing factors. Genetic changes, especially BRCA 1 and 2, make up 10% of breast cancers [9]. Other rare but highly permeable genes include PTEN, TP53, CDH1, and STK11, each leading to a different clinical syndrome [10].
Phosphatase and tensin homolog (PTEN) localized on chromosome 10 (10q23.3) and recognized as tumor
tumors and achieve better local disease control, followed by the definitive therapy of mastectomy of both breasts.
The therapy was chosen to ensure the patient’s more prolonged survival and better prognosis. The limitation of this study is that the patient is still in the evaluation period of post-operative treatment and has not been subjected to a detailed genetic examination.
CONCLUSIONS
This case highlighted multiple primary cancers that are common these days, especially in the same organ, the breast. Nevertheless, medical literature rarely presents a case of synchronous malignancy, prompting us to publish this case. With improved cancer treatment and more prolonged survival, the number of patients with double cancers is increasing.
DECLARATIONS
Ethics approval and consent to participate All participating patients provided written informed consent.
Competing interest
The authors declare no competing interest in this study.
Acknowledgement
The authors wish to thank our institution, Faculty of Medicine, Universitas Sebelas Maret Surakarta for the support.
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