Ipsilateral breast metastasis after axillary dissection caused by epithelioid sarcoma: a case report and pathological investigation
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Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor, commonly occurring in distal extremities, such as fingers, hands and wrists. For oncologists and surgeons, a female patient with enlarged axillary lymph node on one side only is easily diagnosed with an occult breast carcinoma rather than ES. Besides, whole breast metastasis of ES has not been reported yet.
A 47-year-old Chinese woman came to the outpatient clinic of First Affiliated Hospital of Zhejiang University (FAHZU) with a complaint of an asymptomatic right axillary mass for 3 months. Then she received surgical resection of the right axillary lymph nodes and right supraclavicular lymph nodes. According to the clinical tumor site and routine immunohistochemistry (IHC), suspicion of metastatic epithelial sarcoma and metastatic breast cancer could not be ruled out. Subsequently, with more detailed medical history review and physical examination, a mass on the right forearm was found, which was considered as the primary lesion. Further IHC and Molecular Genetics revealed that all the neoplastic cells exhibited loss of INI1 protein and were negative for ERG gene rearrangement yet positive for epithelial membrane antigen (EMA), cytokeratin (CK) 8, CK19, Vimentin, CD34. The final diagnosis was ES. She received postoperative chemotherapy, without radiotherapy. Unexpectedly, an ipsilateral breast metastasis was developed at ten months after surgery. Regrettably, there was no positive result of the metastatic breast sample, based on a genome sequencing by a 381-cancer-gene panel in a lab. Therefore, she went through another round of chemotherapy and took Apatinib for maintenance treatment. During the last follow-up (26 months after diagnosis), the disease was under control.
This rare but interesting case enables breast surgeons and pathologists to accumulate more experience of differential diagnosis of axillary mass for personalized treatment in clinical practice. Meanwhile, ipsilateral breast metastasis of ES we reported in the case urges that clinicians attach greater importance to the tumor metastasis mechanism.
KeywordsEpithelioid sarcoma Axillary mass Breast metastasis
Core needle biopsy
Epithelial membrane antigen
Extraskeletal myxoid chondrosarcomas
First Affiliated Hospital of Zhejiang University
Fluorescence in situ hybridization
GATA binding protein-3
Hematoxylin and eosin
- HMB 45
Human melanoma black 45
- INI 1
Integrase interactor 1
Modified mesna, doxorubicin, ifosfamide and dacarbazine
Epithelioid malignant peripheral nerve sheath tumors
Magnetic resonance imaging
Malignant rhabdoid tumor
Positron emission tomography
Primitive neuroectodermal tumor
- TFE 3
Heavy-chain enhancer 3
Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor originating from mesenchymal tissue with epithelium-like features, which commonly occurs in distal extremities, such as fingers, hands and wrists. It was first described by Enzinger in 1970 . ES grows slowly and presents great metastatic tendency especially in adolescents and young adults. According to case reports, there have been unusual sites with ES metastases such as the vulva , scapular region and pelvis . The majority of patients had initial complaints of skin ulcer and mass. Here we reported a rare case of epithelioid sarcoma with an initial symptom of an axillary mass only, which originated from the right forearm and developed a breast metastasis after a ten-month progression. This case provides information and experience about the diagnosis and treatment of axillary mass for oncologists, surgeons and pathologists, as well as a deeper understanding of the clinical manifestations of ES.
A 47-year-old female patient came to the outpatient clinic of FAHZU with a complaint of an asymptomatic right axillary mass for 3 months. Physical examination revealed a soft mass 4 cm in diameter in the right axilla without any other positive findings in the right breast. An axillary lymph node biopsy was conducted in a previous local hospital, and the histopathological results were suggestive of some metastatic carcinomas with an unknown primary lesion, while suspicion of lobular carcinoma of breast could not be ruled out.
Epithelioid sarcoma is a rare malignant soft tissue tumor with slow progression, which commonly occurs in distal extremities including fingers, hands and wrists. It can migrate to other organs such as lungs and form metastatic lesions through blood vessels and lymphatics . Breast metastasis of ES has not been reported yet.
ES can be classified into two types: distal and proximal types. Distal-type ES usually shows characteristics of nodular aggregates, nests or cords of fairly uniform, plump epithelioid cells, with relatively abundant eosinophilic cytoplasm and distinct central zonal necrosis . Cellular atypia is relatively mild in the primary lesion, compared with a greater degree of pleomorphism in recurrent or metastatic lesions. Proximal-type ES is usually featured by multinodular distributions and sheets of large polygonal cells with mildly to moderately pleomorphic vesicular nuclei and prominent nucleoli. Its key feature is Rhabdoid morphology, and the nodules often contain central necrosis. Although ES can occur in either proximal or distal sites, the tumors rarely contain all features of both types.
Characteristically, ES has immunoreactivity for vimentin and epithelial markers: low and high molecular weight cytokeratins, including keratin 8, keratin 19 and/or EMA. Half of the cases of ES are positive for CD34  and vimentin. The staining pattern suggests that ES is a neoplasm of mesenchymal origin with epithelial dedifferentiation. Almost all cases of ES are negative for ERG gene rearrangement and according to detection by IHC or fluorescence in situ hybridization (FISH), 90% of malignant rhabdoid tumors show nuclear deficiency of INI1 [6, 7], with the inactivation of SMARCB1 .
ES needs to be distinguished from many other benign and malignant diseases. Benign lesions include granulomas , rheumatoid nodules, benign fibrous histiocytomas, and giant cell tumors of tendon sheath. Aside from the morphologic differences between benign lesions and ES, all benign lesions lack CK expression and most lack EMA, both of which are typically diffusely expressed in ES. Malignant diseases include tumors with epithelioid or rhabdoid morphology , such as malignant rhabdoid tumors (MRT), epithelioid malignant peripheral nerve sheath tumors (MPNST), myoepithelial tumors, primitive neuroectodermal tumors (PNET), extra-skeletal myxoid chondrosarcomas (EMC), epithelioid angiosarcomas, epithelioid hemangioendotheliomas (EHE), rhabdomyosarcomas, synovial sarcomas, malignant mesotheliomas, melanomas and so on.
In blood test of ES, Kato et al. documented that 10 of 11 (91%) patients had positive test results for CA-125 [10, 11]. In our case, results of all tumor markers were within normal range. New biomarkers are in need of discovery.
With regard to imaging, twice of PET-CT performed before and after operation were not sufficient to indicate all of the primary and metastatic lesions. Vien X et al. reported a case of proximal-type ES in scrotum with comprehensive staging and monitoring by PET-CT . We speculated that PET-CT was not sensitive enough for the disease and other examinations like CT, MRI and CNB would assist the diagnosis. Moreover, the right axillary mass was considered as a metastasis from a malignant tumor of unknow origin and no mastectomy was performed at the first place. Unexpectedly, the patient developed ipsilateral breast metastasis ten months later which was similar to inflammatory breast cancer, without any other site involved. We wondered whether the metastasis would be avoided or delayed in case mastectomy was performed before. Pathologists showed us that the tumor of right breast puncture under the microscope was totally in the vessel. Since the main lymphatic pathway to the breast had been destroyed after axillary dissection, whole breast metastasis might be caused by residual focus in the breast, as called intra mammary metastasis, explaining the recurrence of the ipsilateral breast. We still wondered why there were no other metastases than the right breast.
As of treatments, Frezza AM et al. considered that anthracycline-based and gemcitabine-based treatments might be of choices . The patient should not be denied of surgery to resect the breast if necessary. Localized radiotherapy should also be the treatment of choice for the disease. Although the genetic testing did not provide positive results, the levels of SWI/SNF complex  or PD-1/PD-L1  in tissue could be evaluated, which may suggest genetic testing as a novel therapy for the disease. This case provides useful and informative clinical reference for breast doctors by presenting a case study of a rare malignant soft tissue tumor.
In conclusion, epithelioid sarcoma is a rare malignant soft tissue tumor. Patients who come to the hospital reporting only enlarged axillary lymph node are easily misdiagnosed with occult breast carcinoma. Our case reported a woman with an axillary metastasis of ES in the right arm. She received a localized operation and classical chemotherapy, and an ipsilateral breast metastasis occurred ten months later. This rare but interesting case enables breast surgeons and pathologists to accumulate more experience of differential diagnosis of axillary mass for personalized treatment in clinical practice. Meanwhile, ipsilateral breast metastasis of ES we reported in our case encourages clinicians to attach greater importance to the tumor metastasis mechanism. For oncologists and surgeons, it is necessary to comprehensively assess the condition, think over the scope of surgery and actively treat the patients.
The authors would like to thank the staff of breast center of the First Affiliated Hospital of Zhejiang University.
LC: collection of clinical data, follow-up of the patient and writing of the manuscript; LW: pathological diagnosis, immunohistochemical analysis and assisted writing; LC and LW contributed equally to this work. XZ, MY: treatment and management of the patient; PF (the last author): treatment, management of the patient and revision of the manuscript. All authors read and approved the final manuscript prior to submission.
This work was supported by National S&T Major Project (NO.2018ZX10301201) and Department of Health of Zhejiang province, China (No.2016RCA013) .
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Written informed consent was obtained from the patient for the publication of the case report.
The authors declare that they have no competing interests.
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