The differential diagnosis of malignant spindle cell neoplasms in the breast most frequently rests between malignant phyllodes tumor (MPT) and metaplastic carcinoma (MBC). Diagnosis of MPT can be challenging due to diffuse stromal overgrowth, keratin (CK) and/or p63 immunopositivity, and absent CD34 expression, which can mimic MBC, especially in core biopsies. Distinction of MPT from MBC has clinical implications, with differences in surgical approach, chemotherapy, and radiation. In this study, we evaluated MPT (78 tumors, 64 patients) for stromal CK, p63, and CD34 expression and profiled a subset (n=31) by targeted next-generation DNA sequencing (NGS), with comparison to MBC (n=44). Most MPT (71%) were CK+ and/or p63+, including 32% CK+ (25/77 focal) and 65% p63+ (32/66 focal, 10/66 patchy, 1/66 diffuse). Thirty-percent of MPT expressed both CK and p63 (20/66), compared to 95% of MBC (40/42, p<0.001). CK and/or p63 were positive in CD34+ and CD34- MPT. Recurrent genetic aberrations in MPT involved TERT, TP53, MED12, CDKN2A, chromatin modifiers, growth factor receptors/ligands, and PI-3K and MAPK pathway genes. Only MED12 (39%, 12/31) and SETD2 (13%, 4/31) were exclusively mutated in MPT and not MBC (p<0.001 and p=0.044, respectively), whereas PIK3R1 mutations were only found in MBC (35%, 13/35, p<0.001). Comparative literature review additionally identified ARID1B, EGFR, FLNA, NRAS, PDGFRB, RAD50, and RARA alterations enriched or exclusively in MPT versus MBC. MED12 was mutated in MPT with diffuse stromal overgrowth (53%, 9/17), CD34- MPT (41%, 7/17), and CK+ and/or p63+ MPT (39%, 9/23), including 36% of CD34- MPT with CK and/or p63 expression. Overall, MED12 mutation and/or CD34 expression were observed in 68% (21/31) MPT, including 61% (14/23) of CK+ and/or p63+ tumors. Our results emphasize the prevalence of CK and p63 expression in MPT and demonstrate diagnostic utility of NGS, especially in MPT with confounding factors that can mimic MBC.

UNASSIGNED: Phyllodes tumors (PTs) are rare breast neoplasms, with an incidence rate of <1 %. Further, the coexistence of PTs and carcinoma is also uncommon. In this report, we describe a rare case of the synchronous coexistence of a benign PT and invasive ductal carcinoma (IDC) of the ipsilateral breast.
METHODS: A 42-year-old woman presented with a 6-month history of a tumor in her right breast. Mammography and ultrasonography revealed a 9.0 cm breast lump, and core biopsy revealed a benign PT. A simple mastectomy of the right breast revealed IDC foci in the mammary area, close to the benign PT. Right axillary lymph node staging was performed by surgery. However, no lymph node metastasis was observed. Subsequently, appropriate adjuvant therapy was initiated. Currently, the patient is doing well.
UNASSIGNED: Breast cancer may be located close to the PT of the ipsilateral breast and is difficult to detect preoperatively, especially in cases of large PTs. Early detection of the presence of a coexisting carcinoma is clinically important because it can alter patient management.
CONCLUSIONS: Careful assessment of the PT using additional breast imaging tools might help identify their coexistence with breast cancer in cases of difficult diagnosis of coexistent tumors using standard breast imaging tools such as mammography or ultrasound.

Presented are three casuistics of seemingly identical breast lesions which even by adopting advanced laboratory techniques may represent diagnostic challenge. Microscopic features of some bland spindle cell lesions of different histogenesis (epithelial or mesenchymal) are misleading and a potential source of unaware errors, which might affect optimal therapeutic strategy. In the setting of three diverse entities (low-grade spindle cell metaplastic carcinoma, desmoid fibromatosis and phyllodes tumor) is documented both demanding diagnostic algorithm and revealing molecular landscape on one side as well as evolving predictive/prognostic parameters on the other one. Close interdisciplinary cooperation is inevitable for accurate interpretation/understanding of revealed diagnostic facts which is required for adjustment of competent rational and individualized therapy.

The transformation of a benign phyllodes tumor (PT) into a malignant PT and/or carcinoma is extremely uncommon. We present a case of a 66-year-old female with a huge mass on the left breast which was successfully removed by surgical resection. The pathological diagnosis was infiltrating lobular carcinoma with pure rhabdoid features and the malignant transformation of a benign phyllodes tumor. The first time this rare case was reported, it is demonstrated a special phenomenon through the synchronous transformation of PT grades and the carcinomatous transformation of PT.

BACKGROUND: Optimal surgical margin width for patients with phyllodes tumors (PTs) of the breast remains debated. The aim of this study was to assess the influence of margin width on long-term local recurrence risk.
METHODS: This was a single-institution retrospective review of patients with confirmed PT treated from 2008-2015. Margins were defined as positive (ink on tumor), narrow (no tumor at inked margin but < 10mm), or widely free (>/= 10mm). LR rates were estimated by the Kaplan-Meier method.
RESULTS: Among 117 female patients, histology included 55 (47%) benign, 29 (25%) borderline, and 33 (28%) malignant PT. Final margins were positive in 16 (14%), narrow in 32 (27%), widely free in 64 (55%), and unknown in 5 (4%) patients. Compared with margins > 10 mm, patients with positive and narrow margins had a higher LR risk [HR 10.57 (95% CI 2.48-45.02) and HR 5.66 (95% CI 1.19-26.99), respectively]. Among benign PTs, the 10-year LR-free rates were 100%, 94%, and 66% for widely negative, narrow, and positive margins, respectively (p = 0.056). For borderline/malignant PT, the 10-year LR-free rates were 93% and 57% for widely negative and narrow margins, respectively (p = 0.02), with no difference in LR between narrow and positive margin groups (p = 1.00).
CONCLUSIONS: For benign PTs, a margin of no ink on tumor appears sufficient to optimize local control. In patients with borderline or malignant PTs, achieving a wide surgical margin may remain important as narrower margins were associated with LR rates comparable to those with positive margins.

Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro. Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo. Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

UNASSIGNED: The lung is the most common site of metastases in the case of phyllodes tumor of the breast followed by bone. However, pneumothorax as a presenting complaint in a patient of bilateral cavitating lung metastases from malignant phyllodes tumor of the breast has never been reported to our knowledge. We herein report a case of a 34-year-old female presenting with sudden onset of chest pain in already existing lung metastases who on imaging showed the development of bilateral pneumothorax. We should, therefore, be on the lookout for the potential development of spontaneous pneumothorax in such cases.

Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, typically characterized by their benign nature. We present a unique case of a 29-year-old Pakistani female who initially presented with a benign PT in her left breast. Despite undergoing multiple surgical resections over the course of a decade, the tumor exhibited a remarkable transformation in biology, progressing from a benign phenotype to malignancy. Subsequent recurrences manifested with increasing aggressiveness, ultimately culminating in distant metastasis to the bones, axillary nodes, chest wall, and abdominal wall. This case underscores the unpredictable nature of PTs and highlights the challenges in managing recurrent cases with malignant transformation. The clinical course described herein emphasizes the importance of vigilant monitoring and individualized treatment strategies in such cases.

UNASSIGNED: Breast phyllodes tumors (BPT) have variable malignant potential, their histological classification remains insufficient for an accurate diagnosis.
UNASSIGNED: We attempted to investigate CD10 (Cluster of differentiation 10) and EGFR (Epidermal growth factor receptor) expression in BPT in order to highlight their diagnostic and prognostic values.
UNASSIGNED: Eight patients with BPT are recruited from January 2014 to December 2020 and immunohistochemical assessment of CD10 and EGFR is realized.
UNASSIGNED: Median age was 27±15.2, the mean tumor size was 9.63±10.21. Only malignant tumours showed expression for EGFR. Borderline and malignant tumors were CD10 positive. Patients overexpressing CD10 were postmenopausal with great tumor size, 25% of these were sarcomatous. Coexistence of CD10 and EGFR overexpression was found in 25% of cases and was associated with age (P=0.008), tumor size (P=0.030) and hitologic types (P=0.014). PC1 and PC2, were extracted, they accounted cumulatively for 94.7% of the variance of the data analysed, it suggests that patient\'s age and histological type of tumor have significant association with CD10 and EGFR expression in BPT.
UNASSIGNED: EGFR and CD10 overexpressed combined proteins in phyllode tumors constitute, with histopathological parameters, an important prognostic factor as well as a promising potential targets.

Phyllodes tumor is an uncommon breast neoplasm that is present in variable sizes. Giant phyllodes are those larger than 10 cm in diameter. Clinically, giant phyllodes tumors present as a visible, rapidly growing mass distorting the breast contour. Such tumors with large size and rapid growth rate suggest a phyllode diagnosis of fibroadenoma. Planning a standard treatment strategy for these tumors is quite challenging. While adequate surgical excision with tumor-free resection margins is the standard of care for most giant phyllodes cases, borderline and malignant giant phyllodes tumors might require wider resections given their high recurrence rates. Some authors described total mastectomy as the treatment option for giant borderline and malignant phyllodes to obtain wide, clear margins. Between March 2022 and September 2023, our surgical oncology department presented and operated on three cases of giant phyllodes. They underwent a nipple-sparing mastectomy and immediate breast reconstruction using pre-pectoral silicone implants. We think that with such a procedure, we can benefit from the wide, safe margins of mastectomy that have been proven to decrease local recurrence rates while considering the aesthetic outcome.