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CAP Home > Case of the Month > 2012 - Case Archives > june_2012_cotm_diagnosis.html

2012 — May Case of the Month

Posted June 12, 2012

CLINICAL SUMMARY: Breast  

CAP Foundation May Online Case of the Month

Click Slide Image to View Case with DigitalScope

After reading the summary, try answering the three related multiple-choice questions below.

A 48-year-old woman with no relevant previous history presented with a right breast mass. A simple mastectomy was performed. Grossly, a 5.0 x 4.8 x 4.0 cm mass well circumscribed mass was present in the retro-areolar region at the junction of the upper outer and inner quadrants. The mass had a tan, homogenous cut surface with “cleft-like” areas grossly visible. Focal gelatinous areas were also seen within the mass. A capsule is identified, but focal areas showed extension of the mass through the capsule into the peri-lesional breast parenchyma. A few satellite nodules were also present in the rest of the breast parenchyma, which appeared to be discrete (non-contiguous) from the larger mass.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 18, malignant phyllodes tumor.

Criteria for Diagnosis and Comments:
The lesion is biphasic with mammary ductal and stromal components. The prominent stromal proliferation compresses the ductal elements into “leaf-like” or phyllodes type of growth pattern. The stroma is predominantly spindled, but in many foci reveals epithelioid cells with malignant cytologic features (enlarged cells with irregular and hyperchromatic nuclear chromatin, marked pleomorphism). Large bizarre and occasional multi-nucleate forms are also present. Mitotic figures, including abnormal mitoses, are seen. This low-power architecture (phyllodes-type growth pattern) and high-power malignant cytologic features are characteristic of malignant phyllodes tumor (MPT).

Phyllodes tumors, as exemplified by this case, are composed of biphasic elements – stromal and glandular. Some pathologists consider that the stromal tumor secondarily evokes a glandular or ductal proliferation. The glandular elements are very characteristically compressed resulting in broad “leaf-like” papillae inserted in cleft-like spaces appreciated in low power examination. Heterologous elements such as adipocytes, smooth muscle, skeletal muscle, cartilage and bone may occasionally be present.

This tumor was initially described as cystosarcoma phyllodes by Johannes Müller in 1838, and has as many as 62 different synonyms. However, the nomenclature suggested by the recent WHO classification is benign, borderline or malignant phyllodes tumor. This breast specimen is a malignant phyllodes tumor.

Most phyllodes tumors follow a benign course, but that the prediction of biologic behavior in a given case can be difficult. The most commonly applied system in this regard is the 3-tiered system. Practically, phyllodes tumors are sub-classified according to the areas of highest cellular activity and most florid architectural pattern. The WHO classification presents the following table helpful in distinguishing between benign, borderline and malignant phyllodes tumor.

 

Benign

Borderline

Malignant

Stromal hypercellularity

Modest

Modest

Marked

Cellular pleomorphism

Little

Moderate

Marked

Mitosis

 

Few if any

Intermediate

Numerous (more than 10 per 10 HPF)

Margins

 

Well circumscribed, pushing

Intermediate

Invasive

Stromal pattern

 

Uniform stromal distribution

Heterogeneous stromal expansion

Marked stromal overgrowth

Heterologous stromal differentiation

Rare

Rare

Not uncommon

Overall age distribution

60%

20%

20%

In the case presented, stromal overgrowth and sarcomatous stroma is very prominent. Occasional mitosis can be seen reaching up to 10 mitosis/10 high power fields.

The prognosis is usually excellent with complete removal, especially with a benign phyllodes tumor. Malignant phyllodes tumor can be associated with frequent recurrences (65% with incomplete removal, 30% complete excision), distant metastatic disease (30%) and rarely death. Multiple chromosomal abnormalities, of which 1q+ and 13q– are the most frequent have been documented in malignant phyllodes tumor, which are not typically seen in benign or borderline phyllodes tumor.

Very rarely, phyllodes tumors can be present in extra-mammary locations. Such extra-mammary phyllodes tumors are mostly seen along the embryological milk-line (a line extending from the anterior axillary fold to the vulva). Whether these tumors arise from remnant breast tissue along this line or they arise primarily as phyllodes tumors without mammary tissue is not clearly known.

The differential diagnosis of phyllodes tumor (PT) includes the entities listed in the master check list. Differentiating low grade phyllodes tumor from fibroadenoma (FA) can be sometimes difficult but the following features are found in PT that are not seen in FA: stromal hypercellularity, stromal overgrowth, prominent leaf-like architecture, stromal condensation around the ducts and infiltration into surrounding breast parenchyma. Pure fibrosarcoma (FS), malignant fibrous histiocytoma (MFH) or mammary-type myofibroblastoma (MTMFB) lack epithelial components, whereas epithelial elements are part of PT. In addition, MTMFB also contains solitary fibrous tumor-like stroma. Metaplastic carcinoma (MC) contains spindled elements which are cytokeratin positive and p63 positive, in contrast to PT. However, squamous differentiation may rarely occur in the epithelial component of PT, and a variety of carcinomas may also be seen arising from PT. Periductal stromal sarcoma (PSS) can resemble stromal elements in phyllodes tumor; however, the ductal elements are open and patent in PSS and leaf like arrangement is rarely, if ever, seen. CD34 and CD117 positivity is seen in a subset of both tumors and so is not a reliable distinguishing feature. In addition, rarely the stromal overgrowth may obscure the leaf-like architectural pattern, and thus make the differential diagnosis difficult.

In summary, phyllodes tumor is composed of biphasic elements, (stromal and epithelial), has a characteristic morphological appearance, with the degree and atypia of stromal elements determining its malignant behavior. Distinguishing benign phyllodes tumor from fibroadenoma and malignant phyllodes tumor can rarely be difficult and subjective. Phyllodes tumor can be present in extra-mammary locations.

A. B. C. D. E.

Supplementary Questions: For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which one of the following is not a helpful feature in distinguishing benign phyllodes tumor from malignant phyllodes tumor: A. High mitotic index
B. Infiltrative margins
C. Sarcomatous growth
D. Squamous differentiation
E. Stromal overgrowth
2. Metaplastic carcinoma can be reliably distinguished from phyllodes tumor by which one of the following feature: A. Atypical spindled cells
B. Cytokeratin positive spindled cells
C. Epithelial ducts interspersed within spindled cells
D. High mitotic index
E. Infiltrative margins
3. Cartilaginous elements are present within a vulvar mass, with prominent stromal elements and a “leaf-like” architecture. Which of the following is correct: A. Phyllodes tumors can be present anywhere in the “milk-line” and can have heterologous elements such as cartilage
B. This cannot be phyllodes tumor, since Phyllodes tumors are restricted to mammary / breast parenchyma only
C. This is a vulvar teratoma
D. This may represent a chondroma or chondrosarcoma
E. Verrucous carcinoma

References

  1. Burga MB, Tavassoli FA. Periductal stromal tumor: A rare lesion with low-grade sarcomatous behavior. Am J Surg Pathol. 2003;27:343-348.
  2. Fiks A. Cystosarcoma phyllodes of the mammary gland – Müller's tumor. For the 180th birthday of Johannes Müller. Virchows Arch A. Pathol Anat Histol. 1981;392:1-6.
  3. Laé M, Vincent-Salomon A, Savignoni A, et al. Phyllodes tumors of the breast segregate in two groups according to genetic criteria. Mod Pathol. 2007;20:435-444.
  4. Lee AH. Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast. Histopathology. 2008;52:45-57.
  5. Mariappan MR, Lagera JE, Fadare O, Sibley RK. A 69-year-old woman with a vulvar lesion. Phyllodes tumor of the vulva. Arch Pathol Lab Med. 2006;130:e11-12.
  6. Tavassoli FA, Devillee P, et al. WHO Classification of Tumours: Pathology and Genetics of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003.

Author:
2009
Kumaresan Cooper, MD
Immunohistochemistry Committee
University of Vermont College of Medicine
Burlington, VT

M. Rajan Mariappan, MD, PhD FCAP
Surgical Pathology Committee
Beth Israel Deaconess Medical Center & Harvard Medical School
Boston, MA

 
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