Epithelial proliferation is a common feature of phyllodes tumours (PTs), but epithelial malignancy is rare. This review seeks to further our understanding of epithelial malignancy within PTs by analysing their histopathological characteristics in previously reported cases and providing an overview of studies on their pathological features. PubMed and DeepDyve were searched for case reports, case series, and literature reviews of in situ and invasive carcinoma within PTs. Only cases where the carcinoma was within the PT were included. Cases of synchronous carcinoma in the ipsilateral or contralateral breast were excluded. Ninety-eight cases of in situ or invasive carcinoma within a PT were identified. Across the grades of PTs, there was a similar proportion of invasive carcinomas compared to in situ lesions. Malignant PT correlates with a higher likelihood of epithelial malignancy, and molecular studies support a possible causal pathophysiological relationship. This higher likelihood may suggest interactions between malignant stroma and the transforming epithelium that could potentially play a significant role in the phenomenon, which remains to be elucidated. Encasement within a PT likely improves the prognosis of breast carcinoma due to earlier detection. The presence of carcinoma within a malignant PT has uncertain prognostic implications. Thorough sampling of all PTs is recommended for appropriate prognostication and management.

Phyllodes tumours (PTs) of the breast are circumscribed fibroepithelial neoplasms showing a prominent and exaggerated intracanalicular architectural pattern with leaf-like stromal fronds demonstrating stromal hypercellularity [1]. In people of European descent, they account for 0.3–1% of all primary breast tumours, with a higher incidence in those of Asian heritage [1]. Of their two components, only the stroma is typically considered neoplastic. It determines their grade of benign, borderline, or malignant, and yet their pathophysiological development likely relies partly on epithelial-stromal interactions. Strong nuclear beta-catenin staining in the stroma of PTs correlates with expression of Wnt (wingless-related integration site) ligands in their epithelium, with the stromal proliferation later becoming independent of the epithelium during malignant progression, suggesting an initial causal link between the epithelium and stromal proliferations via the Wnt-beta-catenin pathway. Malignant transformation of the epithelium may similarly result from de novo epithelial neoplastic progression possibly linked to stromal-epithelial interactions within the PT, or it may represent colonization of a PT by carcinoma arising in the adjacent ducts [2]. While epithelial proliferation is a common feature of PTs, development of epithelial malignancy is rare. Figure 1 depicts histological images of this phenomenon. In a 2005 review, usual ductal hyperplasia of the epithelial component was present in 74% of PTs, while carcinoma occurred in less than 1% [3]. The pathophysiology of these lesions is not fully understood [4, 5].

Fig. 1.

a Invasive ductal carcinoma extending into the stromal frond of a borderline PT. b Low magnification of DCIS at the periphery of a malignant PT.

Fig. 1.

a Invasive ductal carcinoma extending into the stromal frond of a borderline PT. b Low magnification of DCIS at the periphery of a malignant PT.

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This review specifically seeks to further our understanding of epithelial malignancy within PTs by analysing their histopathological characteristics in previously reported cases. It includes discussion of our current understanding of the pathological interactions between the epithelial and stromal components in these rare neoplasms.

PubMed and DeepDyve were searched for case reports, case series, and literature reviews of in situ and invasive carcinoma within PTs. Search terms included PT, cystosarcoma phyllodes, cystosarcoma phyllodes malignum (and variants on spelling), and carcinoma. English and translated non-English abstracts and full texts when available were analysed to identify appropriate cases. Citations and reference lists were used to identify further cases. Only cases where the carcinoma was within the PT were included. Cases of synchronous carcinoma in the ipsilateral or contralateral breast were excluded. Where this distinction could not be made due to imprecise or absent information, for example, in older cases reports when the abstract suggested “coexistence” of a PT and a carcinoma but the full text article could not be found, the paper was excluded. The pertinent data included patient age, the size and grade of the PT, the size and type of the carcinoma, whether it was an in situ or invasive lesion, regional lymph node or distant site involvement, clinical management, and follow-up. Discussions of selected molecular findings were parsed and summarized.

Ninety-eight cases of in situ or invasive carcinoma within a PT were identified in the literature [3‒64], including 31 cases compiled from case series by Sin et al., Widya et al., Co M. et al., Saimura et al., and Nistor-Ciurba et al. [65‒69], as shown in Table 1. Patients averaged 49 years old, ranging from 19 to 80 years. The size of the PT correlated with grade. On average, benign PTs were 57 mm in maximum dimension, borderline were 73 mm, and malignant 78 mm. Of the 98 PTs containing epithelial carcinoma, 40 were malignant (41%), 16 borderline (16%), 34 benign (35%) and no grade was provided in the remaining 8 cases (8%). The PTs contained a range of in situ and invasive carcinomas, which are summarized in Table 2. Seventy-one ductal carcinomas constituted the majority (72%) of lesions, comprising 32 invasive (often with an in situ component) and 39 in situ only. They ranged in size from small foci up to a 110 mm invasive carcinoma present throughout the PT [66]. The grade of invasive carcinoma of no special type (invasive ductal carcinoma/NST) was seldom reported though included grades 1–3. Seventeen PTs contained lobular carcinoma (17%), with 4 invasive lobular carcinomas (ILCs) and 13 lobular carcinomas in situ (LCsIS). The remaining 10% of cases were three PTs containing both DCIS and LCIS (3%), five containing squamous cell carcinomas (5%), one neuroendocrine carcinoma (1%), and one carcinosarcoma (1%) [8, 10, 14, 17, 18, 23, 35, 37, 56, 66].

Table 1.

Published cases of epithelial malignancies within PTs

AuthorsYearAgeSurgeryPT gradeSize, mmEpithelial typeSize, mm*Axillary LN statusTreatmentFollow-up
Treves [61964 Benign LCIS, IDC 
Norris et al. [71967 Invasive carcinoma (2 cases) 
Cornog et al. [81971 Squamous cell carcinoma 
Haagensen [91971 LCIS (two cases) 
Harris et al. [101973 50 Mastectomy Malignant 110 Carcinosarcoma 
Seemayer et al. [111975 27 Mastectomy Malignant 60 DCIS 
Rosen et al. [121975 43 Benign LCIS 
Pietruska et al. [131978 45 Mastectomy Malignant 50 Invasive carcinoma Negative, AD DOD 3 mo, general metastases 
Bassermann et al. [141980 Squamous cell carcinoma 
Leong et al. [151980 51 Mastectomy Benign 40 IDC DF, 21 mo 
Klausner et al. [161983 60 Mastectomy Malignant 40 IDC Negative, AD 
Cole-Beuglet et al. [171983 60 Local excision Benign 14 IDC Focal 
  55 Local excision Benign 35 DCIS, LCIS 
Hunger et al. [181984 57 Mastectomy Malignant 155 SCC 
Ishida et al. [191984 41 Mastectomy Benign 56 IDC Focal Negative, AD Nil DF, 2 yr 6 mo 
Grove et al. [201986 71 Mastectomy Benign 190 DCIS 20 Negative, AD Nil DF, 4 mo 
Ward et al. [211986 55 Mastectomy Malignant 40 LCIS Focal Nil DF, 7 yr 3 mo 
Christensen et al. [221986 Borderline DCIS Foci 
Knudsen et al. [231987 71 Mastectomy Benign 70 DCIS, LCIS Multifocal Negative, AD 
Yasumura et al. [241988 47 Mastectomy Benign 130 IDC Focal Negative (0/13), AD DF, 5 yr 6 mo 
De Rosa et al. [251989 77 Mastectomy Benign 50 DCIS, IDC Negative, AD Nil DF, 10 mo 
Schwickerath et al. [261992 47 Mastectomy Malignant 20 DCIS Negative, AD 
Padmanabhan et al. [271997 47 Mastectomy Malignant 75 LCIS Focal Negative, AD 
Naresh [281997 51 Local excision Borderline 140 DCIS Focal 
Nishimura et al. [291998 80 Mastectomy Malignant 105 DCIS Focal DOD 3 mo, lung/skin metastases of sarcoma 
Alo et al. [302001 39 Mastectomy Malignant 90 DCIS 
Kodama et al. [312003 47 Mastectomy Benign 170 ILC Focal DF, 9 yr 
Parfitt et al. [322004 26 Local excision Benign 33 High grade DCIS, invasive carcinoma NST grade 3 Extensive Positive (4/13) for carcinoma, AD R, H, C DF, 3 yr 
Lim et al. [332005 45 Mastectomy Malignant 120 High grade solid DCIS with comedonecrosis Nil DOOC, 9 yr 
Tokudome et al. [342005 59 Mastectomy Malignant 35 Invasive carcinoma Negative (0/30), AD R, C Recurrence 10 mo carcinoma only, DF, 5 mo post 2nd surgery 
Tan et al. [32005 LCIS 
Tan et al. [32005 Malignant DCIS 
Ramdass et al. [352006 69 Benign SCC 
Nomura et al. [362006 75 Mastectomy Malignant 35 DCIS Negative, AD Nil DF, 26 mo 
Sugie et al. [372007 54 Mastectomy Malignant 80 SCC Negative, AD DOD 40 mo, lung/mouth metastases of sarcoma 
Korula et al. [382008 51 Mastectomy Malignant 160 Low grade DCIS, IDC Positive (2/12) for carcinoma, AD R, H, C DF, 11 mo 
Yamaguchi et al. [392008 54 Mastectomy Benign 150 Cribriform DCIS with comedonecrosis Focal DF, 1 yr 
Macher-Goeppinger et al. [402010 70 Mastectomy Malignant 60 DCIS, IDC 25 Negative, AD Nil Lost to follow-up 
Kuo et al. [412010 24 Mastectomy Borderline 100 DCIS, IDC 25 Positive (1/2) for carcinoma, SLNB H, C DF, 15 mo 
Aziz et al. [52010 43 Local excision Malignant 35 Intermediate cribriform/solid DCIS, invasive carcinoma DCIS foci, carcinoma 2 DF, 1 yr 
Nio et al. [42011 53 Local excision Benign 35 Low-intermediate grade cribriform DCIS DF, 2 yr 
Gina Shirah et al. [422011 49 Local excision Benign 48 LCIS, ILC Nil 
Quinlan-Davidson et al. [432011 53 Local excision Borderline 65 IDC+LCIS IDC 24 Negative (0/3), SLNB 
Choi et al. [442012 62 Mastectomy Malignant 100 Invasive cribriform carcinoma 60 Negative, AD DF, 2 yr 
Shin et al. [452013 42 Benign 18 Cribriform DCIS 12 DF, 8 mo 
Çolakoğlu et al. [462014 19 Local excision Benign 18 Intermediate cribriform DCIS R, H DF, 3 yr 
Prithwijit Ghosh et al. [472014 42 Local excision Benign 22 Intermediate grade DCIS 
Warrier et al. [482015 50 Mastectomy Malignant 110 Intermediate DCIS R, H DF, 2 yr 
Chopra et al. [492016 23 Local excision Benign 50 High grade DCIS Focal Nil 
Sin et al. [652016 43 Mastectomy Borderline 50 DCIS with a small focus of IDC IDC 4 
  45 Mastectomy Borderline 50 DCIS 5 mm 
  46 Mastectomy Borderline 70 DCIS, LCIS, IDC Multiple foci of each, IDC up to 3 
  44 Local excision Borderline 30 LCIS 
  45 Mastectomy Malignant 120 DCIS 
  48 Local excision Malignant 50 LCIS 
Panko et al. [502017 70 Local excision Benign 23 High grade DCIS, IDC Negative, SLNB R, H 
Muthusamy et al. [512017 51 Mastectomy Malignant 155 Invasive carcinoma NST 25 11 positive nodes, AD R, C 
Widya et al. [662017 42 Mastectomy Borderline 150 LCIS Focal Nil DF, 54 moa 
  54 Local excision Benign 60 LCIS Extensive Nil DF, 54 moa 
  75 Mastectomy Malignant 50 Low grade DCIS Nil DF, 54 moa 
  44 Local excision Benign 40 High grade DCIS 2.5 Nil DF, 54 moa 
  49 Mastectomy Malignant 40 Low grade DCIS 40 Nil DF, 54 moa 
  59 Mastectomy Borderline 90 LCIS, high grade DCIS Focal, 11 Nil DF, 54 moa 
  35 Local excision Benign 50 LCIS Focal Nil DF, 54 moa 
  69 Local excision Borderline 40 Low grade DCIS Focal Nil DF, 54 moa 
  58 Mastectomy Borderline 110 Grade 1 IDC 110 Negative, AD R, H DF, 10 yr 
  53 Mastectomy Borderline 50 Intermediate DCIS 0.4–1 foci DF, 54 moa 
  53 Local excision Malignant 10 LCIS Nil DF, 54 moa 
Lui et al. [522018 19 Local excision Benign 50 Low-intermediate DCIS Multifocal Negative (0/2), SLNB 
Fisher et al. [532018 40 Mastectomy Borderline 42 ILC + LCIS 14 Negative, SLNB DF, 6 mo 
Co et al. [672018 54 Mastectomy Borderline 90 Low grade DCIS Focal Nil DF, 70 mo& 
  52 Mastectomy Malignant 100 Intermediate DCIS Focal Nil DF, 70 mob 
  48 Mastectomy Malignant 50 High grade DCIS Focal Nil DF, 70 mob 
  44 Mastectomy Benign 50 Low grade DCIS Focal Nil DF, 70 mob 
  25 Local excision Benign 25 Low grade DCIS Multifocal DF, 70 mob 
  45 Mastectomy Malignant 40 IDC Focal Negative, SLNB Nil DF, 70 mob 
Saimura et al. [682018 32 Local excision Benign 45 Low grade DCIS Nil DF, 4 yr 11 mo 
  49 Local excision Benign 51 LCIS Nil DF, 1 yr 9 mo 
  25 Local excision Benign 40 Low grade DCIS DF, 1 yr 5 mo 
  58 Local excision Benign 37 Low grade DCIS 37 DF, 11 mo 
Hasdemir et al. [542019 Malignant Cribriform/solid DCIS 
  Malignant IDC 
Sun et al. [552019 30 Local excision Benign 15 Intermediate grade DCIS 3.5 Nil DF, 1 mo 
Kaur et al. [562020 26 Local excision Malignant 90 Neuroendocrine carcinoma 45 
Nistor-Ciurba et al. [692020 50 Mastectomy Malignant 110 Grade 3 invasive carcinoma NST + DCIS Negative (0/22), AD R, C DF, 11 yr 
  71 Mastectomy Malignant 50 Grade 1 invasive carcinoma NST Negative (0/16), AD R, H DF, 3 yr 3 mo 
  45 Mastectomy Malignant 60 Cribriform, solid intermediate grade DCIS Negative, SLNB Nil DF, 2 yr 3 mo 
  75 Mastectomy Malignant 40 Grade 2 invasive carcinoma NST + intermediate solid DCIS 20 Negative (0/24), AD R, H DOD 4 yr 8 mo, general carcinoma metastases 
Jesenkova et al. [572021 Malignant IDC Negative, AD R, C DF, 3 yr 
Erdogan et al. [582021 55 Local excision Malignant 70 DCIS Foci DF, 1 yr 
Park et al. [592021 21 Local excision Borderline 20 IDC Negative, SLNB R, H DF, 3 yr 2 mo 
Erdogan et al. [602022 22 Mastectomy Malignant DCIS+IDC Positive for carcinoma (4/19), AD R, H, C DF, 6 yr 
Sazuka et al. [612022 70 Mastectomy DCIS 20 
Brahmachari et al. [622022 36 Mastectomy Benign 45 Cribriform/solid low-intermediate grade DCIS Foci Negative, AD 
Chen et al. [632022 43 Mastectomy Benign 120 ILC 18 Positive for carcinoma (3/13), AD H, C DF, 4 yr 
Gemci et al. [642022 63 Mastectomy Malignant 200 G1 IDC Negative, SLNB DF, 9 mo 
AuthorsYearAgeSurgeryPT gradeSize, mmEpithelial typeSize, mm*Axillary LN statusTreatmentFollow-up
Treves [61964 Benign LCIS, IDC 
Norris et al. [71967 Invasive carcinoma (2 cases) 
Cornog et al. [81971 Squamous cell carcinoma 
Haagensen [91971 LCIS (two cases) 
Harris et al. [101973 50 Mastectomy Malignant 110 Carcinosarcoma 
Seemayer et al. [111975 27 Mastectomy Malignant 60 DCIS 
Rosen et al. [121975 43 Benign LCIS 
Pietruska et al. [131978 45 Mastectomy Malignant 50 Invasive carcinoma Negative, AD DOD 3 mo, general metastases 
Bassermann et al. [141980 Squamous cell carcinoma 
Leong et al. [151980 51 Mastectomy Benign 40 IDC DF, 21 mo 
Klausner et al. [161983 60 Mastectomy Malignant 40 IDC Negative, AD 
Cole-Beuglet et al. [171983 60 Local excision Benign 14 IDC Focal 
  55 Local excision Benign 35 DCIS, LCIS 
Hunger et al. [181984 57 Mastectomy Malignant 155 SCC 
Ishida et al. [191984 41 Mastectomy Benign 56 IDC Focal Negative, AD Nil DF, 2 yr 6 mo 
Grove et al. [201986 71 Mastectomy Benign 190 DCIS 20 Negative, AD Nil DF, 4 mo 
Ward et al. [211986 55 Mastectomy Malignant 40 LCIS Focal Nil DF, 7 yr 3 mo 
Christensen et al. [221986 Borderline DCIS Foci 
Knudsen et al. [231987 71 Mastectomy Benign 70 DCIS, LCIS Multifocal Negative, AD 
Yasumura et al. [241988 47 Mastectomy Benign 130 IDC Focal Negative (0/13), AD DF, 5 yr 6 mo 
De Rosa et al. [251989 77 Mastectomy Benign 50 DCIS, IDC Negative, AD Nil DF, 10 mo 
Schwickerath et al. [261992 47 Mastectomy Malignant 20 DCIS Negative, AD 
Padmanabhan et al. [271997 47 Mastectomy Malignant 75 LCIS Focal Negative, AD 
Naresh [281997 51 Local excision Borderline 140 DCIS Focal 
Nishimura et al. [291998 80 Mastectomy Malignant 105 DCIS Focal DOD 3 mo, lung/skin metastases of sarcoma 
Alo et al. [302001 39 Mastectomy Malignant 90 DCIS 
Kodama et al. [312003 47 Mastectomy Benign 170 ILC Focal DF, 9 yr 
Parfitt et al. [322004 26 Local excision Benign 33 High grade DCIS, invasive carcinoma NST grade 3 Extensive Positive (4/13) for carcinoma, AD R, H, C DF, 3 yr 
Lim et al. [332005 45 Mastectomy Malignant 120 High grade solid DCIS with comedonecrosis Nil DOOC, 9 yr 
Tokudome et al. [342005 59 Mastectomy Malignant 35 Invasive carcinoma Negative (0/30), AD R, C Recurrence 10 mo carcinoma only, DF, 5 mo post 2nd surgery 
Tan et al. [32005 LCIS 
Tan et al. [32005 Malignant DCIS 
Ramdass et al. [352006 69 Benign SCC 
Nomura et al. [362006 75 Mastectomy Malignant 35 DCIS Negative, AD Nil DF, 26 mo 
Sugie et al. [372007 54 Mastectomy Malignant 80 SCC Negative, AD DOD 40 mo, lung/mouth metastases of sarcoma 
Korula et al. [382008 51 Mastectomy Malignant 160 Low grade DCIS, IDC Positive (2/12) for carcinoma, AD R, H, C DF, 11 mo 
Yamaguchi et al. [392008 54 Mastectomy Benign 150 Cribriform DCIS with comedonecrosis Focal DF, 1 yr 
Macher-Goeppinger et al. [402010 70 Mastectomy Malignant 60 DCIS, IDC 25 Negative, AD Nil Lost to follow-up 
Kuo et al. [412010 24 Mastectomy Borderline 100 DCIS, IDC 25 Positive (1/2) for carcinoma, SLNB H, C DF, 15 mo 
Aziz et al. [52010 43 Local excision Malignant 35 Intermediate cribriform/solid DCIS, invasive carcinoma DCIS foci, carcinoma 2 DF, 1 yr 
Nio et al. [42011 53 Local excision Benign 35 Low-intermediate grade cribriform DCIS DF, 2 yr 
Gina Shirah et al. [422011 49 Local excision Benign 48 LCIS, ILC Nil 
Quinlan-Davidson et al. [432011 53 Local excision Borderline 65 IDC+LCIS IDC 24 Negative (0/3), SLNB 
Choi et al. [442012 62 Mastectomy Malignant 100 Invasive cribriform carcinoma 60 Negative, AD DF, 2 yr 
Shin et al. [452013 42 Benign 18 Cribriform DCIS 12 DF, 8 mo 
Çolakoğlu et al. [462014 19 Local excision Benign 18 Intermediate cribriform DCIS R, H DF, 3 yr 
Prithwijit Ghosh et al. [472014 42 Local excision Benign 22 Intermediate grade DCIS 
Warrier et al. [482015 50 Mastectomy Malignant 110 Intermediate DCIS R, H DF, 2 yr 
Chopra et al. [492016 23 Local excision Benign 50 High grade DCIS Focal Nil 
Sin et al. [652016 43 Mastectomy Borderline 50 DCIS with a small focus of IDC IDC 4 
  45 Mastectomy Borderline 50 DCIS 5 mm 
  46 Mastectomy Borderline 70 DCIS, LCIS, IDC Multiple foci of each, IDC up to 3 
  44 Local excision Borderline 30 LCIS 
  45 Mastectomy Malignant 120 DCIS 
  48 Local excision Malignant 50 LCIS 
Panko et al. [502017 70 Local excision Benign 23 High grade DCIS, IDC Negative, SLNB R, H 
Muthusamy et al. [512017 51 Mastectomy Malignant 155 Invasive carcinoma NST 25 11 positive nodes, AD R, C 
Widya et al. [662017 42 Mastectomy Borderline 150 LCIS Focal Nil DF, 54 moa 
  54 Local excision Benign 60 LCIS Extensive Nil DF, 54 moa 
  75 Mastectomy Malignant 50 Low grade DCIS Nil DF, 54 moa 
  44 Local excision Benign 40 High grade DCIS 2.5 Nil DF, 54 moa 
  49 Mastectomy Malignant 40 Low grade DCIS 40 Nil DF, 54 moa 
  59 Mastectomy Borderline 90 LCIS, high grade DCIS Focal, 11 Nil DF, 54 moa 
  35 Local excision Benign 50 LCIS Focal Nil DF, 54 moa 
  69 Local excision Borderline 40 Low grade DCIS Focal Nil DF, 54 moa 
  58 Mastectomy Borderline 110 Grade 1 IDC 110 Negative, AD R, H DF, 10 yr 
  53 Mastectomy Borderline 50 Intermediate DCIS 0.4–1 foci DF, 54 moa 
  53 Local excision Malignant 10 LCIS Nil DF, 54 moa 
Lui et al. [522018 19 Local excision Benign 50 Low-intermediate DCIS Multifocal Negative (0/2), SLNB 
Fisher et al. [532018 40 Mastectomy Borderline 42 ILC + LCIS 14 Negative, SLNB DF, 6 mo 
Co et al. [672018 54 Mastectomy Borderline 90 Low grade DCIS Focal Nil DF, 70 mo& 
  52 Mastectomy Malignant 100 Intermediate DCIS Focal Nil DF, 70 mob 
  48 Mastectomy Malignant 50 High grade DCIS Focal Nil DF, 70 mob 
  44 Mastectomy Benign 50 Low grade DCIS Focal Nil DF, 70 mob 
  25 Local excision Benign 25 Low grade DCIS Multifocal DF, 70 mob 
  45 Mastectomy Malignant 40 IDC Focal Negative, SLNB Nil DF, 70 mob 
Saimura et al. [682018 32 Local excision Benign 45 Low grade DCIS Nil DF, 4 yr 11 mo 
  49 Local excision Benign 51 LCIS Nil DF, 1 yr 9 mo 
  25 Local excision Benign 40 Low grade DCIS DF, 1 yr 5 mo 
  58 Local excision Benign 37 Low grade DCIS 37 DF, 11 mo 
Hasdemir et al. [542019 Malignant Cribriform/solid DCIS 
  Malignant IDC 
Sun et al. [552019 30 Local excision Benign 15 Intermediate grade DCIS 3.5 Nil DF, 1 mo 
Kaur et al. [562020 26 Local excision Malignant 90 Neuroendocrine carcinoma 45 
Nistor-Ciurba et al. [692020 50 Mastectomy Malignant 110 Grade 3 invasive carcinoma NST + DCIS Negative (0/22), AD R, C DF, 11 yr 
  71 Mastectomy Malignant 50 Grade 1 invasive carcinoma NST Negative (0/16), AD R, H DF, 3 yr 3 mo 
  45 Mastectomy Malignant 60 Cribriform, solid intermediate grade DCIS Negative, SLNB Nil DF, 2 yr 3 mo 
  75 Mastectomy Malignant 40 Grade 2 invasive carcinoma NST + intermediate solid DCIS 20 Negative (0/24), AD R, H DOD 4 yr 8 mo, general carcinoma metastases 
Jesenkova et al. [572021 Malignant IDC Negative, AD R, C DF, 3 yr 
Erdogan et al. [582021 55 Local excision Malignant 70 DCIS Foci DF, 1 yr 
Park et al. [592021 21 Local excision Borderline 20 IDC Negative, SLNB R, H DF, 3 yr 2 mo 
Erdogan et al. [602022 22 Mastectomy Malignant DCIS+IDC Positive for carcinoma (4/19), AD R, H, C DF, 6 yr 
Sazuka et al. [612022 70 Mastectomy DCIS 20 
Brahmachari et al. [622022 36 Mastectomy Benign 45 Cribriform/solid low-intermediate grade DCIS Foci Negative, AD 
Chen et al. [632022 43 Mastectomy Benign 120 ILC 18 Positive for carcinoma (3/13), AD H, C DF, 4 yr 
Gemci et al. [642022 63 Mastectomy Malignant 200 G1 IDC Negative, SLNB DF, 9 mo 

IDC, invasive ductal carcinoma, synonymous with invasive carcinoma of NST; NST, no special type; DCIS, ductal carcinoma in situ; LCIS, lobular carcinoma in situ; SCC, squamous cell carcinoma in situ; SLNB, sentinel lymph node biopsy; AD, axillary dissection; R, radiotherapy; H, anti-oestrogen hormone therapy; C, chemotherapy; DF, disease free; DOD, died of disease; DOOC, died of other cause; DFa, DF average follow-up in Widya 2017; DFb, DF average follow-up in Co 2018.

*Where case reports do not give precise dimensions of carcinoma and instead qualify it as focal, multifocal, or extensive, this qualitative measurement has been included as its size.

Table 2.

Number of each type of epithelial malignancy within PTs

Phyllodes gradeDuctal carcinomaLobular carcinomaDuctal and lobularSCCOtherTotal
invasive (NST)in situ disease (DCIS) onlyinvasive (ILC)in situ disease (LCIS) onlyin situ disease
Benign 16 34 
Borderline 16 
Malignant 16 16 40 
Not stated 
Total 32 39 13 98 
Phyllodes gradeDuctal carcinomaLobular carcinomaDuctal and lobularSCCOtherTotal
invasive (NST)in situ disease (DCIS) onlyinvasive (ILC)in situ disease (LCIS) onlyin situ disease
Benign 16 34 
Borderline 16 
Malignant 16 16 40 
Not stated 
Total 32 39 13 98 

Number of each type of invasive and in situ epithelial malignancy within benign, borderline, and malignant PTs, as well as within PTs where the grade was not stated (8 cases). The other category includes a neuroendocrine carcinoma and carcinosarcoma.

A greater proportion of carcinomas within malignant and borderline PTs were invasive compared to benign PTs. Of the 40 carcinomas within malignant PTs, 20 were invasive (50%), compared to 7 of the 16 within borderline tumours (44%) and 12 of the 34 within benign tumours (35%). When restricted to ductal carcinoma only, the most common type of epithelial malignancy, there was a greater proportion of invasive carcinomas within malignant and borderline PTs compared to benign PTs. Within malignant PTs, 16 of 32 ductal carcinomas were invasive (50%), compared to 6 of 13 within borderline (46%) and 8 of 26 within benign (31%).

Fifty-four PTs contained ductal carcinoma in situ (DCIS) – 39 with DCIS only, 3 with DCIS and LCIS, and 12 with an invasive component. For the thirty cases where more detail was available, the DCIS showed variable comedonecrosis, solid and cribriform architecture, and ranged from low to high grade as shown in Table 3. PT grade did not correlate with the DCIS grade and a slightly greater proportion of benign PTs than malignant contained high grade DCIS. Five of sixteen benign PTs contained high grade DCIS (31%), six intermediate grade (38%), and five contained low grade DCIS (31%). Conversely, two of ten malignant PTs contained high grade DCIS (20%), five contained intermediate grade (50%), and three contained low grade DCIS (30%).

Table 3.

Nuclear grade of DCIS within PTs

Phyllodes gradeHigh gradeIntermediate gradeLow gradeTotal
Benign 16 
Borderline 
Malignant 10 
Total 12 10 30 
Phyllodes gradeHigh gradeIntermediate gradeLow gradeTotal
Benign 16 
Borderline 
Malignant 10 
Total 12 10 30 

Nuclear grade of DCIS within malignant, borderline, and benign PTs for which sufficient information was available.

In 34 cases, regional lymph nodes were sampled and examined in either a sentinel lymph node biopsy or axillary dissection (AD) as shown in Table 1. The lymph nodes were involved by metastatic disease in 6 cases, which will be briefly outlined here and summarized in Table 4. In 2004, Parfitt et al. [32] reported a 26-year-old woman who had a benign PT locally excised that contained high grade DCIS and a grade 3 invasive carcinoma NST. 4 of 13 axillary lymph nodes contained carcinoma. The patient underwent radiotherapy, hormone therapy, and chemotherapy and was disease free (DF) at 3 years follow-up. Korula et al. [38] described a 2008 case of a 51-year-old woman who underwent a mastectomy for a malignant PT that contained low grade DCIS and a focus of invasive carcinoma. Two of twelve lymph nodes contained carcinoma and following hormone therapy, radiotherapy, and chemotherapy the patient was DF at 11 months post-surgery. Kuo et al. [41] in 2010 discussed a 24-year-old woman who had a 100 mm borderline tumour resected via mastectomy, which contained a 25 mm invasive ductal carcinoma and DCIS. Carcinoma was present in a sentinel node and the patient was treated with hormone therapy and chemotherapy. She was DF after 15 months. In 2017, Muthusamy et al. [51] reported a 51-year-old woman with a malignant PT containing an invasive carcinoma who underwent a mastectomy and axillary clearance, which revealed 11 positive nodes. She was treated with local radiotherapy and chemotherapy, but her follow-up was not included. A case from Turkey in 2022 by Erdogan et al. [60] detailed the case of a 22-year-old woman with a malignant PT and invasive ductal carcinoma with DCIS. Following a mastectomy and AD, four of nineteen nodes were positive for carcinoma and the patient had radiotherapy, hormone treatment, and chemotherapy and was DF 6 years post-surgery. Finally, in 2022 Chen et al. [63] described the case of a 43-year-old woman with a benign PT containing an ILC, which metastasized to three of thirteen axillary lymph nodes. After hormone and chemotherapy, she was DF at 4 years post-surgery.

Table 4.

Cases with involvement of lymph nodes by metastatic disease

AuthorsAgePT grade and surgeryCarcinomaLymph nodeTreatmentFollow-up
Parfitt et al. [32] (2004) 26 Benign PT, locally excised with AD High grade DCIS and extensive grade 3 invasive carcinoma NST 4 of 13 axillary lymph nodes contained carcinoma Radiotherapy, hormone therapy, and chemotherapy DF at 3 years follow-up 
Korula et al. [38] (2008) 51 Malignant PT, mastectomy with AD Low grade DCIS and a focus of invasive carcinoma 2 of 12 lymph nodes contained carcinoma Hormone therapy, radiotherapy, and chemotherapy DF at 11 months post-surgery 
Kuo et al. [41] (2010) 24 Borderline PT, mastectomy with SLNB 25 mm invasive ductal carcinoma and DCIS Carcinoma was present in a sentinel node Hormone therapy and chemotherapy DF after 15 months 
Muthusamy et al. [51] (2017) 51 Malignant PT, mastectomy, and AD 25 mm invasive carcinoma 11 positive nodes  Local radiotherapy and chemotherapy Follow-up was not included 
Erdogan et al. [60] (2022) 22 Malignant PT, mastectomy, and AD IDC with DCIS 4 of 19 nodes were positive for carcinoma Radiotherapy, hormone treatment, and chemotherapy DF at 6 years post-surgery 
Chen et al. [63] (2022) 43 Benign PT, nipple-sparing mastectomy 18 mm ILC Carcinoma metastasized to 3 of 13 axillary lymph nodes Hormone therapy and chemotherapy DF at 4 years post-surgery 
AuthorsAgePT grade and surgeryCarcinomaLymph nodeTreatmentFollow-up
Parfitt et al. [32] (2004) 26 Benign PT, locally excised with AD High grade DCIS and extensive grade 3 invasive carcinoma NST 4 of 13 axillary lymph nodes contained carcinoma Radiotherapy, hormone therapy, and chemotherapy DF at 3 years follow-up 
Korula et al. [38] (2008) 51 Malignant PT, mastectomy with AD Low grade DCIS and a focus of invasive carcinoma 2 of 12 lymph nodes contained carcinoma Hormone therapy, radiotherapy, and chemotherapy DF at 11 months post-surgery 
Kuo et al. [41] (2010) 24 Borderline PT, mastectomy with SLNB 25 mm invasive ductal carcinoma and DCIS Carcinoma was present in a sentinel node Hormone therapy and chemotherapy DF after 15 months 
Muthusamy et al. [51] (2017) 51 Malignant PT, mastectomy, and AD 25 mm invasive carcinoma 11 positive nodes  Local radiotherapy and chemotherapy Follow-up was not included 
Erdogan et al. [60] (2022) 22 Malignant PT, mastectomy, and AD IDC with DCIS 4 of 19 nodes were positive for carcinoma Radiotherapy, hormone treatment, and chemotherapy DF at 6 years post-surgery 
Chen et al. [63] (2022) 43 Benign PT, nipple-sparing mastectomy 18 mm ILC Carcinoma metastasized to 3 of 13 axillary lymph nodes Hormone therapy and chemotherapy DF at 4 years post-surgery 

SLNB, sentinel lymph node biopsy; IDC, invasive ductal carcinoma.

There were 4 cases of death from metastatic disease and 1 case of disease recurrence without metastases as summarised in Table 5. Pietruska et al. [13] presented the case in 1978 of a 45-year-old woman with an invasive carcinoma within a 50 mm malignant PT who had a mastectomy and AD. There was no lymph node involvement, but unfortunately the patient died from general metastases 3 months post-surgery. The lineage of the metastases was not reported. In 1998, Nishimura et al. [29] described an 80-year-old patient who underwent a palliative mastectomy for a 105 mm malignant PT with focal DCIS involvement and was subsequently placed on hormone therapy for the DCIS. As the surgery was aimed at symptom management, the axilla was not sampled and the patient died from lung and skin metastases of sarcoma 3 months later. In 2005, Tokudome et al. [34] reported a 59-year-old woman with a 35 mm malignant PT containing invasive carcinoma. No lymph nodes out of thirty were involved from an AD and the patient was treated with radiotherapy and chemotherapy. She had a local recurrence of carcinoma 10 months post-surgery and was DF 5 months post the second surgery. Sugie et al. [37] described in 2007 a 54-year-old female with a squamous cell carcinoma within an 80 mm malignant PT with no axillary lymph node involvement who was treated with chemotherapy. Forty months post-surgery, the patient died from generalized lung and mouth sarcoma metastases. Lastly, in 2020 Nistor-Ciurba et al. [69] reported the case of a 75-year-old woman who had a 40 mm malignant PT in the left breast, which contained intermediate grade solid DCIS and a triple negative grade 2 invasive carcinoma, who underwent mastectomy and AD. There was no lymph node involvement and she was treated with radiotherapy. Two and a half years later, she developed a grade 3 invasive carcinoma with 40% staining for oestrogen and progesterone receptors in the right breast. It was unclear whether this was a metastasis from the original malignancy or a new cancer. She had hormone therapy and palliative radiotherapy but died from general metastases of carcinoma almost 5 years after the initial surgery.

Table 5.

Cases with death from metastatic disease or disease recurrence

AuthorsAgePT grade and surgeryCarcinomaLymph nodeTreatmentFollow-up
Pietruska et al. [13] (1978) 45 50 mm malignant PT, mastectomy, and AD Invasive carcinoma No disease in axillary lymph nodes No further treatment recorded Died from general metastases 3 months post-surgery, though their nature was not recorded 
Nishimura et al. [29] (1998) 80 105 mm malignant PT, mastectomy Focal DCIS Not sampled Palliative hormone therapy Died from sarcoma metastases to lung and skin 3 months post-surgery 
Tokudome et al. [34] (2005) 59 35 mm malignant PT, mastectomy, and AD Invasive carcinoma No disease in axillary lymph nodes (0/30) Hormone therapy and chemotherapy Local recurrence 10 months post-surgery, DF at 5 months post 2nd surgery 
Sugie et al. [37] (2007) 54 80 mm malignant PT, mastectomy, and AD Squamous cell carcinoma No disease in axillary lymph nodes Chemotherapy Died of sarcoma metastases to lung and mouth 40 months post-surgery 
Nistor-Ciurba et al. [69] (2020) 75 40 mm malignant PT, mastectomy, and AD Grade 2 invasive carcinoma NST with intermediate-grade solid DCIS No disease in axillary lymph nodes (0/24) Radiotherapy on initial PT in left breast and hormone therapy with palliative radiotherapy on carcinoma in right breast Recurrence or possible new malignancy (invasive carcinoma) in contralateral breast 2.5 years post-surgery, with subsequent death from metastases of carcinoma 4 years 8 months post-surgery 
AuthorsAgePT grade and surgeryCarcinomaLymph nodeTreatmentFollow-up
Pietruska et al. [13] (1978) 45 50 mm malignant PT, mastectomy, and AD Invasive carcinoma No disease in axillary lymph nodes No further treatment recorded Died from general metastases 3 months post-surgery, though their nature was not recorded 
Nishimura et al. [29] (1998) 80 105 mm malignant PT, mastectomy Focal DCIS Not sampled Palliative hormone therapy Died from sarcoma metastases to lung and skin 3 months post-surgery 
Tokudome et al. [34] (2005) 59 35 mm malignant PT, mastectomy, and AD Invasive carcinoma No disease in axillary lymph nodes (0/30) Hormone therapy and chemotherapy Local recurrence 10 months post-surgery, DF at 5 months post 2nd surgery 
Sugie et al. [37] (2007) 54 80 mm malignant PT, mastectomy, and AD Squamous cell carcinoma No disease in axillary lymph nodes Chemotherapy Died of sarcoma metastases to lung and mouth 40 months post-surgery 
Nistor-Ciurba et al. [69] (2020) 75 40 mm malignant PT, mastectomy, and AD Grade 2 invasive carcinoma NST with intermediate-grade solid DCIS No disease in axillary lymph nodes (0/24) Radiotherapy on initial PT in left breast and hormone therapy with palliative radiotherapy on carcinoma in right breast Recurrence or possible new malignancy (invasive carcinoma) in contralateral breast 2.5 years post-surgery, with subsequent death from metastases of carcinoma 4 years 8 months post-surgery 

The pathophysiology leading to the occurrence of epithelial malignancy within PTs is unclear, whether it is due to de novo neoplastic transformation of epithelium or colonization by adjacent carcinoma. One study concluded that an invasive ductal carcinoma and malignant PT were true collision tumours. The malignant stroma of the PT showed loss of heterozygosity at chromosomes 16q23, 17q12, 17q25, and 22q13, and while the non-carcinomatous epithelial component shared the loss of heterozygosity at 16q23, the invasive carcinoma did not exhibit the divergent alleles at 16q23, 17q12, and 17q25, indicating a lack of clonality between the PT and invasive ductal carcinoma [40]. Despite this, a large number likely result from transformation of the epithelium. A high proportion of carcinomas within the PTs were ductal carcinomas, both invasive and in situ, which correlates with their high incidence as primary breast cancers worldwide. Similarly, 5% of the carcinomas were ILC and 5–15% of all breast carcinomas are lobular [70]. In a previous large single-centre review of 605 PTs, 73% were benign, 18% borderline, and 9% malignant [71]. In contrast, in the current review 41% of the PTs containing carcinoma were graded as malignant and only 35% as benign. This may suggest that a greater proportion of malignant PTs harboured epithelial malignancy and the process is not solely driven by colonization as that would likely result in a similar distribution of PTs of different grades containing epithelial malignancy to the previous review. Previous molecular studies have postulated a pathophysiological relationship between the epithelium and stroma of PTs. Strong nuclear beta-catenin staining in the stroma of PTs correlates with expression of Wnt ligands in their epithelium, with the stromal proliferation later becoming independent of the epithelium during malignant progression [2]. Progression from benign PTs to borderline and malignant PTs can be driven by genes such as PIK3CA, RB1, TP53, NF1, PTEN, BRAF, and EGFR [72]. In a case of invasive carcinoma NST within a borderline PT, mutations in the PIK3CA gene were present in both the epithelial and stromal components. Such mutations are present in 49% of luminal A tumours and also implicated in malignant progression of PTs [73]. Furthermore, Dietrich elucidated clonal abnormalities in both the epithelium and stroma of PTs, while Kuijper also demonstrated monoclonality in PT epithelium. These findings suggest the possible presence of a putative precursor cell with epithelial-stromal plasticity that may be the origin of diverse neoplastic components of the lesion [74].

Corresponding to these suggested pathophysiological links, there was a correlation between phyllodes tumour grade and the presence of invasive carcinoma. Borderline and particularly malignant PTs were more likely to contain an invasive carcinoma (as opposed to an in situ lesion) than a benign PT. However, benign PTs intriguingly contained high grade DCIS more often than malignant phyllodes. A parallel inverse association between the degree of epithelial hyperplasia and PT grade has previously been noted [3, 33]. Combined with the above review results and previous molecular studies, it is possible that malignant stroma could interact with the neoplastic epithelium and play a part in its malignant transformation. Whether it truly has an influence over the subsequent progression and grade of the epithelial malignancy remains to be further clarified.

The prognostic implications of these lesions are interesting. From the standpoint of breast carcinoma, encasement within a larger fibroepithelial mass accentuates size and likelihood of earlier clinical or radiological detection and thus feasibly confers a positive prognostic benefit [20, 31, 37, 41, 49]. The cases within this review are consistent with this theoretical benefit. Fifty-six cases described an invasive carcinoma within the PT. As previously outlined, in six of these cases (11%) the tumour metastasized to the axillary lymph nodes. For the five where follow-up data were available, all were DF at the reported interval though admittedly the follow-up periods were short. Only 1 of these 56 cases (2%) developed generalized metastatic carcinoma and died from their disease. From the standpoint of the PT, a malignant PT likely has a similar risk of local recurrence, distant metastasis, and subsequent prognosis, with or without an in situ carcinomatous component [33]. There is also no evidence that invasive carcinoma worsens the prognosis of a malignant PT when there is appropriate surgical and systemic treatment for the carcinomatous element. The prognosis of patients with PT containing in situ disease with clear surgical margins is reportedly excellent [62].

Currently, treatment is non-standardized and decided on a case-by-case basis [38, 40]. From the literature, treatment decisions were guided first by the presence of invasive carcinoma, entailing a sentinel lymph node biopsy and/or AD with radiotherapy, chemotherapy, and/or hormone therapy, as well as by the phyllodes tumour grade, with adequate local surgical control and close monitoring for recurrence and distant metastases, often omitting lymph node assessment if only in situ epithelial disease is noted [33, 37, 40, 60]. This is because lymph node metastasis for PTs is rare and AD not a standard treatment [37, 54]. Indeed, there were no recorded instances of sarcoma involvement of the lymph node in the reviewed 98 cases compared to 5 cases in which there were carcinoma deposits. Often, radiotherapy [58, 68] or occasionally hormone therapy [62] was added for DCIS.

The review has multiple limitations reducing the power of its conclusions. Changes in nomenclature and grading systems of PTs, as well as only sporadic reporting of features such as DCIS grade, axillary lymph node status, and follow-up, reduced the data available for analysis. Reporting of cases regarded as more likely to appeal to journals may have also skewed the findings. The data were difficult to access for some previous cases because only an abstract or title of a paper was available. Beyond these practical difficulties, sample sizes were necessarily small due to rarity, and the retrospective design of the review is subject to inherent selection biases.

Epithelial malignancy within PT is a rare phenomenon. When present, ductal carcinoma is the most common type. The pathogenesis of concurrent epithelial malignancy within PTs remains poorly understood with analysis hampered by small sample sizes and incomplete reporting. Interactions between neoplastic stroma of PTs and the transforming epithelium may play a role in the development of this phenomenon, which remains to be further elucidated and understood. Despite this, malignant PTs appear to have a greater likelihood to contain epithelial malignancy than those of benign grade. A key conclusion is that thorough sampling and careful histological evaluation of PTs are recommended, not only for accurate grading but also to identify potential concurrent epithelial malignancies for appropriate treatment.

We wish to thank Dr. Mihir Gudi from Kandang Kerbau Women’s and Children’s Hospital for contributing the cases from which the figures were taken.

The authors have no conflicts of interest to declare.

No funding was obtained for the review.

Dr. William Cook conducted the literature search and analysis including its discussion and conclusions. He drafted the review including text and figures and compiled the final version after editing and evaluation by the two supervising authors. Dr. Cheok Soon Lee is the Head of Department at Liverpool Hospital where the review was compiled. He supervised and edited drafts of the review, including suggested interpretations of the compiled data. Dr. Puay Hoon Tan is an international expert in phyllodes tumours and proposed the review. She also supervised and edited drafts of the review, including suggested interpretations of the compiled data.

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