Malignant Phyllodes Tumors of the Breast With Rhabdomyosarcomatous Differentiation: A Case Report and Literature Review.

Phyllodes tumor (PT) is a rare fibroepithelial breast neoplasm that is typically graded histopathologically as benign, borderline, and malignant. Malignant PTs (MPTs) exhibit marked stromal cellularity, atypia, overgrowth, increased mitotic activity, and the propensity to metastasize. MPTs represent 10%-15% of all PT cases and often have a notably aggressive disease course. Infrequently, these tumors contain heterologous histological elements, including liposarcoma and fibrosarcoma, among others. Rhabdomyosarcomatous differentiation is an exceptionally rare example of such variation. This report documents the clinical presentation and disease course of a 62-year-old woman diagnosed with MPT with rhabdomyosarcomatous differentiation, just the seventh such confirmed case in the English literature. The patient experienced an arduous disease course, developing metastases to her lungs and axial skeleton just months after her initial diagnosis. Palliative radiation and chemotherapy were initiated, but the patient unfortunately succumbed to her disease just 10 months after the initial diagnosis. This case adds to the scarce literature surrounding the rare development of a heterologous rhabdomyosarcomatous element in an MPT, as well as the decision-making process surrounding the use of radiation to treat such lesions. The details discussed in this paper may inform future approaches for patients diagnosed with this disease.

Massive malignant phyllodes tumor accompanied by anemia and ulceration in the breast: A case report.

Large malignant breast phyllodes tumors are uncommon in clinical settings. Here, we report such a case to provide a reference for clinical work. A 48-year-old woman identified a lump in her right breast, which eventually grew up to 25 cm × 10 cm and began to rapidly bleed and ulcerate within 3 months. The patient had visible signs of anemia and significant emaciation as a result of the tumor's wasting effect and the protracted course of the disease. The patient underwent a modified radical mastectomy on the right breast. The pathology results obtained after surgery revealed a malignant phyllodes tumor. No adjuvant therapy, such as chemotherapy or radiation, was administered. The patient had no symptoms of tumor recurrence and complications from the surgery after a follow-up of 9 months.

Malignant phyllodes tumor with EGFR variant III mutation: A rare case report with immunohistochemical and genomic studies.

A female in her 60's presented with a left-sided breast mass. A core needle biopsy specimen showed diffuse proliferation of a round cell tumor, which was positive for vimentin, NKX2.2, BCOR, and focal CD99 on immunohistochemistry (IHC). No fusion genes of the Ewing family sarcomas were detected. With a tentative diagnosis of primary breast sarcoma (PBS), total mastectomy was performed after chemotherapy. The resected tissues showed proliferation of round or spindle-shaped tumor cells with a high nuclear-to-cytoplasmic ratio, exhibiting solid and fascicular arrangements but no epithelial component or organoid pattern. While IHC indicated no particular histological diagnosis, genomic examination revealed gene alterations in MED12 p.G44D, MLL2 (KMT2D) p.T1496fs*27, and EGFR variant III (vIII). Moreover, a retrospective IHC study showed overexpression of EGFRvIII. A malignant phyllodes tumor (PT) with extensive sarcomatous overgrowth was indicated as an integrative diagnosis. This is a rare case of a malignant PT harboring EGFRvIII. The present case provides an importance of accurate diagnosis and genomic analysis of rare breast tumors, as malignant PT and PBS are different in its treatment strategy and prognosis.

Multi-recurrent Asynchronous Bilateral Malignant Phyllodes.

In this comprehensive study, we present an exceptionally rare case characterized by the occurrence of multi-recurrent asynchronous bilateral malignant phyllodes tumors. Phyllodes tumors, known for their rapid growth, originate within the stromal tissue of the breast and predominantly manifest as benign entities. Our case stands out as an extraordinary anomaly, not only due to its bilateral malignant nature but also owing to the manifestation of a multi-recurrent pattern on both sides. This unprecedented presentation underscores the complexity and heterogeneity of malignant phyllodes tumors, necessitating further in-depth investigation to unravel the underlying mechanisms driving their aggressive behavior and to explore innovative therapeutic strategies aimed at optimizing patient outcomes and prognosis.

Malignant Phyllodes Tumor in a Pubertal Girl: A Report of a Case.

BACKGROUND: Malignant phyllodes tumor (MPT) is a rare breast disease that is extremely rare in children. A few cases of pediatric malignant phyllodes tumors have been reported, including some with a poor prognosis. CASE: A 14-year-old girl presented with a growing lump on her right breast. On the basis of imaging tests and a core needle biopsy, MPT was diagnosed, and right mastectomy was performed. The postoperative course was uneventful. SUMMARY AND CONCLUSION: MPT is an infrequent disease in adult females and is extremely rare in pubertal females. It occasionally shows rapid growth, metastasis, and recurrence with a poor prognosis. Early surgical resection is necessary to obtain a cure. When a rapidly growing breast tumor is observed in pubertal females, MPT should be considered.

Better survival was found in patients treated with breast-conserving surgery compared with mastectomy in malignant phyllodes tumor of the breast.

Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer. The prognosis between breast-conserving surgery (BCS) and mastectomy remains unclear in MPTB. Therefore, long-term survival was investigated between BCS and mastectomy in MPTB via the Surveillance, Epidemiology, and End Results (SEER) database. MPTB patients with T1-2/N0 stage between 2000 and 2015 from SEER database were retrospectively reviewed. Prognosis between different surgical approaches was assessed by Kaplan-Meier curves and Cox proportional hazards analysis. A total of 795 patients were enrolled with a median follow-up of 126 months. BCS was associated with significantly increased 10-year overall survival (OS) (89.2% vs. 81.1%, p = 0.002) and breast cancer-specific survival (BCSS) (95.2% vs. 90%, p = 0.004) compared with mastectomy. Multivariate analysis showed better OS (HR = 0.587, 95% CI 0.406-0.850, p = 0.005) and BCSS (HR = 0.463, 95%CI 0.267-0.804, p = 0.006) in the BCS group than the mastectomy group. After 1:1 propensity score matching (PSM), improved 10-year OS (89.2% vs.81%, p = 0.023) and BCSS (95.8% vs. 90.1%, p = 0.033) were observed in BCS compared with mastectomy. This study found the survival benefit of BCS over mastectomy in patients with early-stage MPTB. BCS should be recommended as a priority in MPTB patients when both surgical approaches are feasible.

Malignant phyllodes tumor of the breast in ayoung patient ­ case report

Phyllodes tumor (PT) is an uncommon form of breast tumor. It occurs most commonly in women aged 35 to 65 years. The benign form represents about 85­90% of cases and only 10­15% of PTs are malignant. Clinically and radiologically, malignant phyllodes tumor (MPT) presents as regular, well-delimited, mobile nodules that are difficult to distinguish from fibroadenomas of the breast. The most important differential diagnoses of MPT include fibroadenoma, metaplastic carcinoma, and sarcoma. The prognosis of MPT exhibits a higher frequency of local recurrence and metastatic rate with larger tumors and inadequate surgical margins. The case presented here refers to a 24-year-old female patient, with a vast tumor in the right breast, with rapid and progressive growth, associated to local pain, and histological diagnosis of MPT. Surgery was the initial treatment, followed by adjuvant chemotherapy and radiotherapy. The purpose of this article was to report an atypical case of MPT of the breast in a very young woman as well as to make a brief literature review on this infrequent and dangerous disease. (AU)

Clinical perspectives and outcomes of the giant breast phyllodes tumor and sarcoma: a real-world retrospective study.

BACKGROUND: Giant breast malignant phyllodes tumor or sarcoma (GBPS) are rare entities with diameter larger than 10 cm and variously histological pleomorphisms. This disease poses a significant threat to the quality of life of individuals, and its prognosis remains unclear. This study aimed to explore the differential diagnosis, treatment, and prognosis of GBPS in a real-world retrospective cohort. METHODS: We collected GBPS (diameter > 10 cm, n = 10) and BPS (diameter ≤ 10 cm, n = 126) from patients diagnosed with sarcoma or malignant phyllodes tumor between 2008 and 2022. We analyzed clinical characteristics, histological status, treatment, and local recurrence using the Fisher's exact test between GBPS (diameter > 10 cm) and BPS (diameter ≤ 10 cm) cohort. We described overall survival (OS) and disease-free survival (DFS) using Kaplan-Meier curves and identified risk factors for local recurrence using logistic regression. The tumor size, age at diagnosis, and differential immunohistochemistry markers of breast sarcoma or phyllodes tumor to determine the prognosis of GBPS. RESULTS: In our retrospective analysis of breast malignancies, we identified 10 cases of GBPS and 126 cases of BPS, corresponding to a GBPS prevalence of 0.17% (10/6000). The median age was 38.5 years (inter-quartile range, IQR: 28.25-48.5 years). During the follow-up of period (median: 80.5 months, IQR: 36.75-122 months), the local recurrence (LR) rate was 40% and 20.6%, respectively. Clinical characteristics of young age (HR:2.799, 95%CI -00.09276-0.017, p < 0.05) and cytological characteristics of marked stromal atypia (HR:0.88, 95% CI 0.39-1.40, p < 0.05) were risk factors for the poor prognosis of GBPS by COX regression model analysis. The Kaplan-Meier curves of GBPS 5-year disease-free survival (DFS) and overall survival (OS) were 31.5 months and 40 months, respectively, and were not associated with adjuvant radiation or chemotherapy. CONCLUSION: We recommend mastectomy with a clear surgical margin as the preferred treatment for GBPS. Age and stromal atypia are significantly associated with recurrence. Adjuvant radiation therapy is advised; however, there was no improvement in overall survival. There is no consensus on the effectiveness of adjuvant chemotherapy and genetic methods, highlighting the need for further research into this aggressive tumor. We recommend a multidisciplinary approach involving a dedicated team for the management of GBPS.

Organoid models derived from patients with malignant phyllodes tumor of the breast.

PURPOSE: Phyllodes tumor of the breast is a kind of rare neoplasm, which accounts for less than 1% of all breast tumors. Malignant phyllodes tumor (MPT) is the highest risk subtype of phyllodes tumor, and is characterized by the tendency of local recurrence and distant metastasis. The prediction of prognosis and the individual therapy for MPT is still challenging. It's urgent to develop a new reliable in vitro preclinical model in order to understand this disease better and to explore appropriate anticancer drugs for individual patients. METHODS: Two surgically resected MPT specimens were processed for organoid establishment. MPT organoids were subsequently subjected to H&E staining, immunohistochemical analysis and drug screening, respectively. RESULTS: We successfully established two organoid lines from different patients with MPT. The MPT organoids can well retain the histological features and capture the marker expression in original tumor tissues, including p63, vimentin, Bcl-2, CD34, c-Kit, and Ki-67, even after a long-term culture. The dose titration tests of eight typical chemotherapeutic drugs (paclitaxel, docetaxel, vincristine, doxorubicin, cisplatin, gemcitabine, cyclophosphamide, ifosfamide) on the two MPT organoid lines showed patient-specific drug responses and varying IC50 values. Of all the drugs, doxorubicin and gemcitabine showed the best anti-tumor effect on the two organoid lines. CONCLUSION: Organoids derived from MPT may be a novel preclinical model for testing personalized therapies for patients with MPT.

Case report: Osteosarcomatous differentiation in the lung metastasis of a malignant phyllodes tumor.

Malignant phyllodes tumor is a rare breast tumor, with distant metastases and heterologous differentiation in a few cases. We report a case of malignant phyllodes tumor with liposarcomatous differentiation in the primary tumor and osteosarcomatous differentiation in the lung metastatic tumor. A middle-aged female presented with a well-defined mass in the upper lobe of the right lung measuring 5.0 × 5.0 × 3.0 cm. The patient had a history of malignant phyllodes tumor in the breast. The patient underwent a right superior lobectomy. Histologically, the primary tumor was a typical malignant phyllodes tumor with pleomorphic liposarcomatous differentiation, while the lung metastasis showed osteosarcomatous differentiation without original biphasic features. The phyllodes tumor and heterologous components showed CD10 and p53 expression, and were negative for ER, PR, and CD34. Exome sequencing revealed TP53, TERT, EGFR, RARA, RB1, and GNAS mutations in all three components. Although the lung metastasis were morphologically different from the primary breast tumor, their common origin was demonstrated through immunohistochemical and molecular characterization. Cancer stem cells give rise to tumor heterogeneous cells, and heterologous components in malignant phyllodes tumors may indicate unfavorable prognosis and a greater risk of early recurrence and metastasis.

Malignant phyllodes tumor of the breast with heterologous osteosarcoma and chondrosarcomatous differentiation: A rare case report with imaging findings.

Phyllodes tumors of the breast are rare fibroepithelial neoplasms accounting for 0.3%-1.5% of all female breast tumors [1,2]. Malignant transformations occur in 10%-20% of phyllodes tumors, often in the form of stroma. Heterologous osteosarcoma and chondrosarcomatous differentiation of phyllodes tumor are extremely rare, and little is known about their imaging findings. Here, we report a rare case of a 52-year-old woman with no history of previous surgery or radiation therapy, who presented with a rapidly growing right breast mass that was diagnosed as a malignant phyllodes tumor with heterologous osteosarcoma and chondrosarcomatous differentiation. The patient underwent modified radical mastectomy.

New Staging System and Prognostic Model for Malignant Phyllodes Tumor Patients without Distant Metastasis: A Development and Validation Study.

PURPOSE: To build a new staging system and new prognostic models for MPTB. METHODS: We performed a comprehensive analysis of the data from the SEER database. RESULTS: We discussed the characteristics of MPTB by comparing 1085 MPTB cases with 382,718 invasive ductal carcinoma cases. We established a new stage- and age-stratification system for MPTB patients. Furthermore, we built two prognostic models for MPTB patients. The validity of these models was confirmed through multifaceted and multidata verification. CONCLUSIONS: Our study provided a staging system and prognostic models for MPTB patients, which can not only help to predict patient outcomes, but also enhance the understanding of the prognostic factors associated with MPTB.

A rare case of metastatic malignant phyllodes tumor with osteosarcomatous differentiation presenting with intestinal obstruction.

Phyllodes tumors (PTs) are uncommon biphasic breast neoplasms constituting 0.5 to 1.0% of all breast tumors. Malignant PTs form a very small proportion of these and may metastasize, especially to the lungs and bones. Aggression and metastatic potential are accentuated in tumors exhibiting heterologous differentiation. Metastases to the gastrointestinal tract (GIT) have seldom been reported and are often confined to a segment of the digestive tract. In the absence of relevant clinical history, such patients presenting with gastrointestinal symptoms can lead to diagnostic perplexities. We report a unique case of a malignant PT with extensive osteosarcomatous differentiation and widespread metastases to the GIT.

Lymph Node and Distant Metastases in Phyllodes Tumor of the Breast.

A 54-year-old woman who incidentally noticed a "knot" in her left breast subsequently underwent excisional biopsy which yielded a diagnosis of malignant neoplasm with sarcomatous features. Given the broad differential diagnosis and imaging findings, the patient underwent bilateral mastectomy and intraoperative sentinel lymph node assessment. An 8.5 cm tumor that was further classified as a malignant phyllodes tumor was identified in the left breast, while the frozen section interpretation came back as positive for metastatic disease which resulted in left axillary lymphadenectomy. Two months later the patient progressed to distant metastatic disease and unfortunately passed away within 6 months after her initial diagnosis. Lymph node metastasis in phyllodes tumor is an exceptionally rare event for which patients usually do not undergo intraoperative sentinel lymph node examination; however high clinical suspicion of metastatic disease would be evidence for further investigation.

Classic illustrations of benign and malignant phyllodes breast tumors in two patients.

Phyllodes tumors, World Health Organization fibroepithelial tumors, are classified as benign, borderline, or malignant based on histopathology. Phyllodes must be distinguished from benign fibroadenomas, also WHO fibroepithelial tumors. The distinction of phyllodes from fibroadenomas can be challenging clinically, as these tumors may mirror one another. Here, we present 2 cases, classic clinical and imaging examples of benign and malignant phyllodes, to review the current epidemiology, classification, diagnosis, and treatment of phyllodes tumors.

Intragenic EGFR::EGFR.E1E8 Fusion (EGFRvIII) in 4331 Solid Tumors.

Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2-7) is a recurrent intragenic EGFR::EGFR.E1E8 fusion that occurs in high-grade gliomas. The presence of EGFRvIII in other solid tumors has not been well characterized. We retrospectively reviewed advanced malignant solid tumor cases tested by a custom hybrid capture 610-gene next-generation sequencing platform from 2021 to 2022. EGFRvIII was identified in 17 of 4331 (0.4%) cases, including 16 of 238 (7%) brain tumors and 1/301 (0.3%) breast tumors. EGFRvIII-positive brain tumors were all glioblastoma IDH-wildtype, most with concurrent TERT promoter mutation (14 of 16), EGFR amplification (13 of 16), and EGFR mutation (8 of 16). The only EGFRvIII-positive breast lesion was a sarcomatoid neoplasm in a young female patient. A separate breast case tested outside our institution with reported EGFRvIII was noted in a young female patient with a malignant phyllodes tumor with stromal overgrowth. Microscopically, both EGFRvIII-positive breast tumors showed high-grade sarcomatoid morphology with brisk mitotic activity. In summary, EGFRvIII is rare, occurring primarily in glioblastoma and rarely in breast sarcomatoid neoplasm, with no instances identified in other tumor types in our series. This select group of patients may benefit from chemotherapy and/or targeted anti-EGFR therapy.

Metastatic Phyllodes Tumor in a Patient With Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic disorder of imprinting on the chromosome 11p15 region that presents with clinical features, such as macroglossia, abdominal wall defects, neonatal hypoglycemia, hemihypertrophy, and embryonal tumors. Phyllodes tumors (PTs) are rare fibroepithelial tumors that account for 0.3% to 1% of breast tumors and present in women aged 35 to 55 years. Here we describe a rare case of metastatic malignant phyllodes tumor in a 27-year-old woman with BWS and uniparental disomy (UPD) of chromosome 11p15.5. To our knowledge, this is the first case report in literature to describe metastatic malignant phyllodes tumor in a woman with BWS.

Genomic characteristics of two breast malignant phyllodes tumors during pregnancy and lactation identified through whole-exome sequencing.

BACKGROUND: The genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations. METHODS: DNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes. RESULTS: In total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTEN and TP53). PTEN and TP53 may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, including FCHO1 in Patient 1, and LRP12 and PKM in Patient 2, were pathogenic. Several genes, including FCHO1, LRP12 and PKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant in PRF1, was detected in Patient 1. CONCLUSION: Our study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, including TP53 mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy, TP53 and PTEN. One germline mutation in PRF1 was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.

Malignant phyllodes tumor of the breast with metastases to the lungs: A case report and literature review.

Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breasts. Approximately 10%-15% of PTs are malignant, and 9%-27% of patients with malignant PTs, develop metastatic disease. The lungs are the most common target organ for distant metastasis of PT. We report a case of 44-year-old female with a malignant PT. It had recurred locally 3 times, and 3 relapses occurred 13 months after the first diagnosis, presenting multiple metastases to the lungs by CT scan. The patient underwent radiation therapy, and palliative chemotherapy with doxorubicin was initiated. Two courses of doxorubicin therapy were administered, but the patient expired 16 months after PT diagnosis. We present a rare case of malignant PT with local recurrences, lung metastases, and poor patient outcome. Although malignant breast PTs have an unfavorable prognosis, adjuvant radiotherapy combined with margin-negative resection may be associated with decreased local recurrence and distant metastasis rates. Future research should include randomized clinical trials or well-designed prospective matched studies to clarify the effectiveness of treatments of PTs.