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Year : 2017  |  Volume : 60  |  Issue : 3  |  Page : 371-376
Malignant phyllodes tumor with heterologous differentiation: Clinicopathological spectrum of nine cases in a tertiary care institute in Eastern India

1 Department of Pathology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

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Date of Web Publication22-Sep-2017


Phyllodes tumors are uncommon fibroepithelial neoplasms of breast. Heterologous sarcomatous differentiation of malignant phyllodes tumor (MPT) is a rare phenomenon as shown in the literature. Herein we report a series of nine cases from a tertiary care centre in Eastern India. Patients demographic data and clinical details were obtained from the medical records. Histopathology and immunohistochemical studies were analysed and diagnosed accordingly. Out of 38 cases of PT, 13 were found to be MPT, of which 9 cases showed heterologous differentiation in the form of angiosarcoma, fibrosarcoma, undifferentiated sarcoma, extensive squamous differentiation and with lipomatous metaplasia. Proper diagnosis and subtyping of the sarcomatous component is essential for deciding the correct treatment modality and prognostication of the disease. However there is no clear cut treatment protocol is available because of paucity of data.

Keywords: Heterologous, malignant, phyllodes, transformation

How to cite this article:
Nayak M, Patra S, Mishra P, Sahoo N, Sasmal PK, Mishra TS. Malignant phyllodes tumor with heterologous differentiation: Clinicopathological spectrum of nine cases in a tertiary care institute in Eastern India. Indian J Pathol Microbiol 2017;60:371-6

How to cite this URL:
Nayak M, Patra S, Mishra P, Sahoo N, Sasmal PK, Mishra TS. Malignant phyllodes tumor with heterologous differentiation: Clinicopathological spectrum of nine cases in a tertiary care institute in Eastern India. Indian J Pathol Microbiol [serial online] 2017 [cited 2023 Mar 30];60:371-6. Available from:

   Introduction Top

Phyllodes tumor are uncommon fibroepithelial lesions accounting for ≤1% of all primary breast neoplasms.[1] WHO classifies it into benign, borderline and malignant based on tumor border, stromal cellularity and overgrowth, nuclear atypia, mitotic activity and the presence of malignant heterologous elements. These tumors have a tendency to recur. Majority of recurrence is histologically similar to the initial tumor, however malignant transformation with heterologous differentiation though rare has been described.

Despite the fact that malignant phyllodes tumor (MPT) can undergo heterologous differentiation, an extensive literature review showed few case reports only. Herein we report a series of nine cases in a duration of 2 years from a tertiary care centre in Eastern India. This study analyses the clinicopathological features in patients of phyllodes tumor with special reference to heterologous elements.

   Materials and Methods Top

This is a retrospective study conducted in the Department of Pathology over a period of 2½ years from January 2014 to June 2016. Patients demographic data, family history, history of previous breast disease, prior treatment history, detail surgical procedure and follow up data were obtained from the medical records. During this period 38 cases of phyllodes tumors were diagnosed. They were classified into benign, borderline and malignant using the parameters put forth by WHO 2012 classification. Routine hematoxylin and eosin stained sections were made with 10% neutral buffered formalin as fixative. The mastectomy specimens were grossed as per CAP protocol. Immunohistochemistry was performed using panel of antibodies (DAKO) which included pancytokeratin, vimentin, epithelial membrane antigen, smooth muscle actin, desmin, myogenin, S-100, P63, CD31, CD34, BCL-2 and CD117 wherever indicated.

   Results Top

Out of 38 cases diagnosed with phyllodes tumor, 23 cases were benign, 2 were borderline and 13 were malignant. Of the 13 cases diagnosed as malignant phyllodes, 9 cases showed heterologous differentiation and 4 cases were usual malignant phyllodes without differentiation. The diagnosis of all the nine cases are enlisted in [Table 1]. Detailed clinical history and mammographic findings of all nine cases are tabulated in [Table 2].
Table 1: The various heterologous transformation seen in our cases

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Table 2: Clinical history and mammographic findings of all nine cases

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Two cases revealed phyllodes admixed with sarcomatous components of a vasoformative tumor [Figure 1]c. The latter composed of anastomosing vascular channels lined by spindloid cells with elongated plump to oval, pleomorphic, hyperchromatic, mitotically active nuclei, eosinophilic cytoplasm with ill-defined cytoplasmic borders. Some of the cells showed neo lumina formation with extensive areas of hemorrhage and necrosis. Plenty of polymorphs admixed with the tumor component were seen. The tumor cells were strongly positive for CD31 favouring a diagnosis of “angiosarcoma” [[Figure 1]c, Inset]. The younger patient, showed features of lactational changes with cytoplasmic vacuolation and hobnailing of the nuclei [Figure 1]d.
Figure 1: (a and b) Gross. (c) Anastomosing vascular channels lined by pleomorphic spindle cells (H and E, ×400). Inset CD31 (×400). (d) Lactational changes (H and E, ×40)

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An isolated case of fibrosarcomatous transformation with stromal overgrowth and hypercellularity was seen. The cells were spindle shaped arranged in interlacing bundles, fascicles and in herringbone pattern resembling fibrosarcoma [Figure 2]c. The cells were elongated to oval with hyperchromatic nuclei, scanty cytoplasm and indistinct cell border and no tumor giant cell [Figure 2]d. Extensive areas of hemorrhage and necrosis were seen. These features were consistent with a diagnosis of “malignant phyllodes with fibrosarcomatous transformation.”
Figure 2: (a and b) Gross. (c and d) Tumor cells in intersecting fascicles and herringbone pattern (H and E, ×100, ×400)

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Two cases were diagnosed as MPT with undifferentiated sarcomatous transformation. The sarcomatous component revealed long fascicles of spindle cells intersecting at right angles. These cells had hyperchromatic, pleomorphic nuclei with dense eosinophilic fibrillary cytoplasm [Figure 3]b and [Figure 3]c. Few cells were polygonal with abundant amount of eosinophilic cytoplasm and the cells were seen palisading around areas of geographic necrosis. Epithelioid cells, binucleated and multinucleated tumor giant cells were seen admixed with the pleomorphic spindle cells [Figure 3]d. Tumor cells were only positive for vimentin and negative for smooth muscle actin, desmin, myogenin, S-100, bcl-2, CD117 and CD34 and hence was diagnosed as MPT with undifferentiated sarcomatous transformation. Adjascent breast showed features of lactational changes.
Figure 3: (a) Gross. (b) Tumor cells in intersecting fasicles (H and E, ×100). (c) Binucleated and multinucleated tumor giant cells admixed with pleomorphic spindle cells (H and E, ×100). (d) Multinucleated tumor giant cells (H and E, ×400)

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There was a single case of malignant phyllodes with extensive squamous differentiation. The stromal cells were spindloid in shape arranged in long fascicles and storiform pattern. The spindle cells showed moderate nuclear pleomorphisim and tumor giant cells. Within the stroma there were islands of squamous differentiation exhibiting hyperkerotosis, parakeratosis, dyskeratosis and formation of keratin pearls [Figure 4]c. In addition to squamous metaplasia, the ductular epithelium also showed hyperplasia of usual ductal type. Though the transition between myoepithelial cells and squamous cells were not easily identified, the IHC expression of P63 in both the myoepithelial cells and the metaplastic squamous cells supports the myoepithelial origin of the metaplastic squamous cells in concordance with literature [Figure 4]d.[2]
Figure 4: (a and b) Gross. (c) Squamous metaplasia (H and E, ×40 Inset - P63 positivity). (d) Spindle cells, ducts and keratin (IHC, ×100)

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Three cases showed a tumor composed of ductular and stromal components. Stromal component showed spindle cells arranged in bundles, fascicles and storiform pattern [Figure 5]b. One of the section showed cells with intracellular accumulation of fat which were S100 positive [Figure 5]d and intervening areas were myxoid [Figure 5]c. However the lipomatous component did not reveal any lipoblast in all the three cases. However in one case the periphery of the tumor showed areas of multinucleated bizzare tumor giant cells, resembling pleomorphic sarcoma. Extensive areas of hyalinization and coagulative necrosis were seen. Resected margins were free of tumor. The ductules were compressed into slit like spaces, lined by cuboidal to columnar epithelium with focal stratification and few ducts were dilated containing eosinophilic secretions. [Table 3] summarizes the patient's histopathological data and follow-up.
Figure 5: (a) Gross. (b) Lipomatous metaplasia (H and E, ×100), (c) Storiform pattern (H and E, ×100). (d) S100 positivity by the tumor cells (IHC, ×400)

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Table 3: Summarizes the patient's histopathological data and follow up

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   Discussion Top

Heterologous sarcomatous differentiation of malignant phyllodes is a rare phenomenon, which comprises of angiosarcoma, liposarcoma, chondrosarcoma, rhabdomyosarcoma or osteosarcoma.[3] The number of phyllodes tumor reported during pregnancy is low.[4] However in this series we report three cases of MPT during pregnancy and two of them showed heterologous differentiation.

The incidence of primary angiosarcomas of breast is 0.04% of primary breast tumors and approximately 8% of breast sarcomas.[5] Angiosarcoma arising in MPT is extremely rare and constitutes <1% of all breast tumors [6] and only three cases have been reported till date.[7],[8],[9] Surprisingly we reported two cases of angiosarcomatous transformation in a short span of 2 years. According to Barrenetxea et al.[10] 12% of angiosarcoma occurs in pregnancy which implies a hormonal effect. However, reported cases with positive hormone receptors are so rare that the hormonal dependency of angiosarcoma is still debated.[7] In addition to the hormonal receptors other factors which may play a role for rapid transformation during pregnancy are suppressed immune system and placental growth factors. The case of concern was in the third trimester of pregnancy and the hormonal receptors were negative on tumour tissue.

Till date only four cases of fibrosarcoma arising from phyllodes has been documented to the best of our knowledge after a thorough literature search,[11],[12],[13],[14] which suggests the prognosis for fibrosarcoma of the breast is poor and the treatment modality is not well defined due to insufficient data of this disease.[15] Established therapeutic guidelines used for both soft tissue sarcoma and breast cancer should be applied in the management of fibrosarcoma.[15] Tumor size is an important prognostic factor than tumor grade.[16] Distant metastasis is seen in 28.6% of patients with malignant phyllodes.[17] Surprisingly in our case though the tumor size was 27 cm in maximum dimension, the patient did not have distant metastasis. The most common site of distant metastasisis is lung. As with soft tissue sarcomas, distant pulmonary metastasis may be resectable for cure if it is the only site of distant disease.[18],[19]

MPT with undifferentiated sarcomatous transformation is extremely rare and has not been repoted so far in literature to the best of our knowledge till date. We are reporting two such cases. The closest differential diagnosis in this case was metaplastic carcinoma with spindle cell differentiation, which was ruled out considering the absence of malignant glandular elements and pancytokeratin negativity in the tumor cells. It is important to distinguish the two entities because of different management protocols.

At the initial workup of the primi her radiological workups were negative for distant metastasis. After 12 months postsurgery the patient was admitted for right chest pain and left pelvic pain. The contrast enhanced computed tomography thorax, abdomen and pelvis showed disseminated metastatic disease with right pleural effusion, bilateral multiple nodules in the lung parenchyma, multiple hypodense lesions in the liver and osteolytic lesions in the left ileum, iliac crest, sacrum and right femoral head. Needle biopsy was done from left iliac swelling showed spindle cells in long fascicles and infiltrating the bony fragments. A diagnosis of metastatic MPT was rendered and the patient was referred to the department of radiotherapy. As the tumor was aggressive, with marked pleomorphisim and high proliferative activity with an average mitotic rate of 18–20/10 HPF including atypical mitotic figures, this could be a possible explaination for early distant metastasis in our patient.

In malignant phyllodes several proliferative changes including hyperplasia, adenosis or squamous metaplasia are occasionally seen in the lining epithelia.[20] Squamous metaplasia of ductal epithelium which may occur in benign, borderline and MPT has been found in 10% of phyllodes.[3] In one of the reported phyllodes tumor series stromal metaplasia was observed in 3.3% of cases that included benign adipocytic and chondromyxoid elements, malignant heterologous elements such as chondroid, osteoid, rhabdomyosarcoma and liposarcoma where as the epithelial component showed ductal hyperplasia in 36.5% of cases and squamous metaplasia was observed only in 3.6% of the cases.[21] Here we encountered a rare case of malignant phyllodes with extensive squamous metaplasia of the myoepithelial origin. There is no difference in the treatment protocol compared to the usual cases of malignant phyllodes.

Most of the literature on lipomatous differentation in phyllodes is liposarcomatous [22] with a handful of cases showing adipose metaplasia. No tumor recurrences were seen in the MPT with adipocytic differentiation.[23] All the three cases showed lipomatous metaplasia without any lipoblast. The patients are on close follow-up and no recurrences are documented at 6 months follow-up.

Proper histopathological diagnosis and subtyping of the sarcomatous components are essential for deciding the correct treatment modality and prognostication of patients with MPT. Pregnancy related hormones may have some relation with exacerbation and aberrant differentiation, but the mechanism of which is not clear. Further studies involving larger series and deep molecular analysis may help in predicting the biological behavior of these tumors and as well as for development of targeted therapy.

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Conflicts of interest

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   References Top

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Barrenetxea G, Schneider J, Tánago JG, Pérez C, Centeno MM, Rodríguez-Escudero FJ. Angiosarcoma of the breast and pregnancy: A new therapeutic approach. Eur J Obstet Gynecol Reprod Biol 1995;60:87-9.  Back to cited text no. 10
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Correspondence Address:
Susama Patra
Department of Pathology, All India Institute of Medical Sciences, Bhubaneswar, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_426_16

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3]

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