Malignant Phyllodes Tumor of the Breast with Anemia and Unexplained Fever: A Case Report and Literature Review

doi:10.21203/rs.3.rs-2062085/v1

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Case Report

Malignant Phyllodes Tumor of the Breast with Anemia and Unexplained Fever: A Case Report and Literature Review

https://doi.org/10.21203/rs.3.rs-2062085/v1

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The PT, which is a rare tumor accounting for approximately 1% of all breast tumors, could be classified as benign, junctional, or malignant based on stromal morphology. Herein, we reported a 52-year-old woman with an enlarged breast mass within 2 months to 90 x 50 mm, accompanied by cachexia and a fever. And clinicopathological findings included progressive erythrocyte drop and hypoproteinemia after hospitalization, no defined causative agent by various laboratory tests as well as no definite diagnosis even through FNA cytology and local biopsy. After symptomatic treatment, mastectomy and axillary lymph node dissection were performed, and postoperative pathological diagnosis suggested MPT with ER(-), PR(-), HER-2(-), KI67(30%+), P63(-), CK5/6(-), EMA(-), and P53(+), subsequently conventional chest radiotherapy treatments were executed (radiation dose: CTV 50Gy/25F) about 25 procedures. However, lung metastasis appeared just a few months later re-accompanied by fever and other symptoms. Therefore,a case report and literature review of malignant phyllodes tumor are presented herein to lead to increased awareness and recognition of this disease.

Breast Cancer

Malignant Phyllodes Tumor

Pulmonary Metastasis

Anemia

Hypoproteinemia

Neoplastic fever

PT, which is defined as a fibrous epithelial tumor with a lobulated appearance, requires surgical treatment regardless of which type of PT including benign, junctional, and malignant ¹. MPT is an intractable problem because of its high local recurrence rate and potential ability to metastasize ². In addition, existing treatment options are not standardized, and chemotherapy lacks sensitivity. Whereas radiotherapy is reported to be effective for OS and DFS of MPT. Due to the low incidence rate, patients with malignant phyllodes tumors accompanied by unexplained fever and progressive hematocrit decline are even rarer. In this paper, we report a case of a patient with a MPT with cachexia as well as pulmonary metastases in the short term after mastectomy and axillary lymph node dissection and a full course of radiotherapy, as a warning that the prognosis for this type of tumor is extremely poor.

1. Breast Lump

The patient was a 52-year-old postmenopausal woman with a right breast mass that was found 2 months ago and rapidly increasing in size. Before admission, ultrasound showed a large irregular mass of about 90×50mm in the right breast, BI-RADS classification: category 4C, and enlarged axillary lymph nodes with suspected metastasis. After admission, the MRI of the breast was perfected: the right breast mass was considered to be a PT with a high probability of BI-RADS category 5(Figure 1). Fine needle aspiration suggested that spindle cell tumor tended to be malignant PT could not be excluded. Immunohistochemistry: Vim (+), CK (-), ER (-), PR (-), HER2 (-), P120 (+), E-cadherin (-), p53 40%, (+), Ki67 5% (+). Biopsy of the right breast mass suggested: a high malignant spindle cell tumor, tending to be a malignant lobulated tumor. Immunohistochemistry suggested: CK (-), CD10 (+), CK5/6(-), ER (-), PR (-), HER2 (-), SMA (+), Ki67 20% (+) (Figure 2C-D).

2. Concomitant symptoms

During the disease, the patient developed a fever with no apparent cause a month ago, peaking at 38.3°C. On the third day after admission, the patient developed intermittent fever with temperature fluctuations of 37°-39.6°C, accompanied by sweating, coughing, and coughing up a small amount of white foamy sputum (Figure 3D). The patient was questioned and told that she had a history of tooth extraction two months ago. Based on the available clinical features, the patient was considered to have an infectious fever caused by tooth extraction or active tuberculosis. We considered that the fever might be infectious caused by tooth extraction or active tuberculosis. At this point, we started anti-infective treatment with ceftizoxime and related laboratory tests. However, blood culture and sputum culture as well as nodule test results were negative, only C-reactive protein and procalcitonin concentrations were elevated in the range of (179-307 mg/L and 0.4-0.92), IL-6 and IL-10 were elevated (100.53 pg/ml, 8.5 pg/ml), respectively, while routine blood and liver and kidney function tests were repeatedly performed on the patient during this period. The patient's red blood cells, hemoglobin and albumin were found to be progressively decreasing (Figure 3A-C). The hematologic team performed tests related to blood disorders, including reticulocytes, coombs test, antinuclear antibody profile, whole body lymph node ultrasonography, and bone marrow aspiration. The only result was elevated ferritin (1069 ng/ml), no associated hematologic disorders were detected, and the cause of the anemia was unknown. After symptomatic treatment with anti-infection and transfusion of hemoglobin and albumin during hospitalization, the patient's overall physical condition continued to decline progressively.

3. Postoperative condition

After multidisciplinary discussion as well as PET/CT evaluation for the absence of metastasis, the patient underwent right mastectomy and axillary lymph node dissection on the 19th day after admission. Postoperative pathological examination suggested a malignant tumor in the right breast, with epithelial components seen in the focal area, tending to be MPT. No cancer metastasis was seen in the axillary lymph nodes (0/15). Immunohistochemistry: ER (-), PR (-), HER-2 (-), KI67 (30%+), CK (-), P63 (-), CK5/6 (-), CD56 (-), CD68 (-), CD31 (+), CD34 (-), CKL (-), CKH (-), Vim (+), P53 (+) (Figure 2E-H). There was no postoperative fever as well as a progressive decrease in hematocrit and hemoglobin, with increasing mental status day by day.

4. Postoperative follow-up

The patient was discharged from the hospital and continued with 25 conventional chest radiotherapy sessions (radiotherapy dose: CTV 50Gy/25F). In the 3rd month after the completion of radiotherapy, the patient's chest CT was repeated, suggesting that there was no definite sign of recurrence in the operated area and multiple small nodules in both lungs, considering the possibility of metastasis (Figure 4A). However, the patient did not pay attention to it. At the end of the postoperative period, the patient had a repeat CT scan, which showed a nodule of approximately 4.8 cm × 3.8 cm × 5.2 cm in size in the anterior segment of the upper lobe of the left lung and multiple nodules in both lungs (Figure 4B). At present, the patient has symptoms of fever, dry cough, fatigue and sweating, and of course, the red blood cells and hemoglobin are progressively decreasing. There is a high clinical suspicion of tumor metastasis recurrence. The patient is currently undergoing systemic comprehensive treatment in the oncology department.

PT of breast origin is associated with mammary fibroepithelial tumors and is classified as benign, mixed, or malignant in histology. Of these, benign PT is more common, accounting for approximately 40-50%³. It has been reported that all PTs can recur, except for a higher rate of local recurrence in junctional PT and MPT⁴. Zhang et al. reported a high rate of distant metastasis in MPTs of up to 22%⁵. However, lymph node metastases are less common in these tumors, usually hematogenous metastases to the lung and bone⁶. We did not find any lymph node metastases in this patient during We also did not find any lymph node metastasis when we performed a lymph node biopsy on this patient.

The presentation of PT is more similar to that of fibroadenomas on imaging, and ultrasound and mammography are not able to diagnose the benignity or malignancy of PT⁷. A history of rapid tumor growth and pathologic diagnosis is required, but the lack of standardized criteria for this tumor and the use of fine-needle aspiration due to the many cytologic features shared by this tumor and common fibroadenomas make the diagnosis of PT a bit of a challenge⁸. pathologists have some diagnostic headaches. Usually combined with immunohistochemistry, p53, Ki-67, CD117, and EGFR have a high positive rate in malignant tumors^9,10. Breast spindle cell tumors are composed of sarcomatoid spindle and epithelial adenocarcinoma cells and are also carcinosarcomas. Because MPT is also a type of tumor in which malignant mesenchymal cells proliferate, they are diagnostically indistinguishable from sarcomas¹¹. Therefore, puncture and local mass biopsy would suspect spindle cell tumors in our case. For the differentiation of the two, they can be identified by keratin and P63 in immunohistochemistry¹².

For PT, surgical resection is the main treatment in clinical practice. For the definition of margin size, a current multi-institutional review on PT suggests that for junctional line and MPT the margin should be ≥1 cm wide for local excision or mastectomy¹³. There is no standardized adjuvant treatment modality for this type of tumor. No significant benefit of chemotherapy for this tumor can be seen in previous reports. Whereas radiotherapy may have the greatest benefit in patients with lobar tumors who opt for breast-conserving surgery or may reduce the rate of local recurrence in patients with larger masses, data from Chaney et al. showed that 43% of patients with lobar tumors larger than 5 cm and stromal overgrowth developed distant metastases⁵. Kapiris et al. also reported that postoperative adjuvant radiotherapy is often considered for MPTs, but the overall survival benefit was not significant¹⁴.

Neoplastic fever is a paraneoplastic syndrome, and for this unexplained fever, the fever is characterized by intermittent fever¹⁵. There are no relevant characteristic indicators to determine the diagnosis of this type, and other factors need to be excluded before the final determination can be made, which is clinically quite difficult¹⁶. For the mechanism of tumor fever, some investigators currently propose that it is due to the release of TNF, IL-1, IL-5, and interferon by tumor cells. , interferons, and other pyrogenic sources¹⁷. Elevated IL6 and IL-10 were indeed seen in our patients. It has also been documented that procalcitonin is useful in differentiating tumorigenic fever from infectious fever, and the median procalcitonin level in their non-infectious tumorigenic fever group was ≤0.5 mg/L¹⁸. This is more consistent with the procalcitonin concentration in our patient. Tumor fever presenting with only elevated inflammatory markers and no elevated infectious markers would have been rare¹⁹. Rapidly growing PT of the breast invading the skin has been reported with anemia²⁰. Both Liu and Laila et al. have reported PT metastasizing to the stomach and presenting with anemia^6,21. However, its occurrence in the setting of negative systemic evaluation is rare and has not been reported. In this patient, postoperatively, the fever, as well as the anemia, had improved on their own, the hemoglobin was found to be within the normal range during the follow-up of the patient, and the physical condition was improving day by day. Within a year, the patient developed a mass in the lung, and the accompanying fever, progressive hemoglobin decline, and hemoglobin decreased. The mechanism is to be further investigated and discovered. In this case, the tumor behavior could be predicted by molecular and gene expression, which unfortunately we did not do at that time.

In conclusion, PT is a very rare disease, even rarer in breast cancer with fever, progressive hemoglobin decline, and hypoproteinemia and without systemic metastases. Surgical intervention should be performed as early as possible for this type of disease, and this case developed pulmonary metastases 3-4 months after surgery. We are reminded of the need to understand that the prognosis of patients with tumor fever is extremely poor.

Acknowledgements

None

Authors’ contributions

LZH prepared and wrote the article and prepared the images. JN revised the manuscript and acted as corresponding author. ZXH wrote and reviewed the manuscript. All authors contributed to this article and approved the submitted version

Funding

None

Availability of data and materials

The authors declare that all data supporting the findings of this study are available within the article.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Chongqing Medical University.

Consent for publication

Informed consent for publication was attained from the patient.

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

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Malignant Phyllodes Tumor of the Breast with Anemia and Unexplained Fever: A Case Report and Literature Review

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Abstract

Figures

Introduction

Case Presentation

1. Breast Lump

2. Concomitant symptoms

3. Postoperative condition

4. Postoperative follow-up

Discussion

Declarations

References

Additional Declarations

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