Nonepithelial Malignancies of the Breast

May 1, 2004

Chugh and Baker have presenteda concise and contemporaryreview of the commonnonepithelial malignancies of thebreast, focusing mainly on the managementof this heterogeneous groupof neoplasms. Needless to say, appropriatemanagement of any neoplasmis entirely dependent on accurate pathologicdiagnosis. Due to the rarity ofthese nonepithelial malignancies of thebreast, they commonly present difficultiesin pathologic diagnosis. Issuesrelating to the diagnosis of these tumorsmay not be obvious to nonpathologists,and deserve comment.

Chugh and Baker have presenteda concise and contemporaryreview of the commonnonepithelial malignancies of thebreast, focusing mainly on the managementof this heterogeneous groupof neoplasms. Needless to say, appropriatemanagement of any neoplasmis entirely dependent on accurate pathologicdiagnosis. Due to the rarity ofthese nonepithelial malignancies of thebreast, they commonly present difficultiesin pathologic diagnosis. Issuesrelating to the diagnosis of these tumorsmay not be obvious to nonpathologists,and deserve comment.Classification of NonepithelialMalignancies of Breast
The stroma of the breast includesblood vessels, fibroblasts, smoothmuscle, peripheral nerves, and last butcertainly not least, adipose tissue. Acomplete list of all possible nonepithelialmalignancies of the breastwould be a lengthy one and wouldinclude angiosarcoma, fibrosarcoma,leiomyosarcoma, peripheral nervesarcoma, and liposarcoma. Pathologicclassification of these tumors remainsproblematic. One need onlynote that Chugh and Baker list malignantfibrous histiocytomas amongthe most common subtypes of breastsarcomas-however, the very existenceof malignant fibrous histiocytoma as a pathologic entity has beenquestioned.[1]The authors have classified nonepithelialmalignancies of the breast intofive basic categories: primary breastsarcoma, secondary (therapy-related)sarcoma, phyllodes tumor, primarylymphoma, and angiosarcoma. Thisclassification may be helpful from aclinical perspective but is overly (andovertly) simplistic from a pathologicstandpoint. For instance, primarybreast sarcomas encompass a complex(and dizzying) array of tumors.Classification of these tumors may bedependent on the pathologist's understandingof histogenesis or differentiation.For example, liposarcoma inthe breast is uncommonly primary andmost often represents liposarcomatousdifferentiation in a malignant phyllodestumor.[2]Clinicopathologic Correlation
The pathologist entrusted with thediagnosis of nonepithelial malignanciesof the breast ought to possess allpertinent clinical information. Theavailability of clinical history, eg, previoussarcoma or radiation, is crucialfor accuracy in diagnosis. Some nonepithelialmalignancies in the breastcould represent metastatic tumors.Radiation has been associated withcertain stromal tumors including theso-called malignant fibrous histiocytoma.Information regarding physicalexamination and radiologic findingsmay be important in establishing theappropriate pathologic diagnosis. Cutaneous(from skin overlying breast)or osseous (from a rib underlyingbreast) neoplasms may simulate primaryintramammary nonepithelialmalignancies.Knowledge of the patient's clinicalhistory is critical for the diagnosisof so-called "atypical vascular lesion"-a lesion described in the skinoverlying the breast following irradiation.[3] These lesions may be difficultto distinguish from low-gradeangiosarcomas. Clinical presentationas a discrete cutaneous lesion, a shortinterval between irradiation and presentation,and subtle histologic differencesare helpful in establishingthe apposite diagnosis.Phyllodes Tumor
As Chugh and Baker have indicated,the pathologic diagnosis of phyllodes(fibroepithelial) tumor must bequalified as benign, borderline, or fullymalignant-a distinction determinedby the tumor's cellularity,stromal overgrowth, mitotic activity,and cytologic atypia. However, theoverriding determinant of prognosisis the assessment of margins: The fundamentalgoal of therapy for all formsof phyllodes tumor is complete excisionto prevent recurrence.Second Opinion
Pathologic diagnosis of some formsof nonepithelial malignancies may bechallenging. For example, a certaintype of epithelial malignancy (metaplasticspindle cell carcinoma) maysimulate a nonepithelial malignancy.As a matter of fact, this tumor hasbeen referred to as a "fibromatosislike"carcinoma.[4] The diagnosis ofthis tumor may require confirmatoryimmunostaining with high-molecularweightcytokeratin, but above all else,requires awareness of the entity onthe part of the pathologist.In terms of incidence, malignanciesof epithelial origin vastly outnumberthose of nonepithelial(stromal) origin-the latter comprise< 5% of all breast cancers. Owing totheir rarity, nonepithelial malignanciesare uncommonly encountered bypathologists in routine practice. Rarediagnoses require diagnostic affirmationby ancillary techniques, and mayalso require a second opinion from anexpert well versed in the diagnosticnuances of such neoplasms.[5]Optimistic Note
A notable silver lining in the otherwisedark cloud of nonepithelialmalignancies of the breast is the expectationthat with the advent of sentinellymphadenectomy, Stewart-Treves syndrome (ie, angiosarcomaprimarily in the upper extremity followinglymphedema) has been relegatedto the pages of textbooks ofmedical history.Nonepithelial malignancies of thebreast are uncommon. Accurate pathologicdiagnosis, crucial for the managementof this group of tumors,should always be based on clinicalinformation.

Disclosures:

The author has no significantfinancial interest or other relationshipwith the manufacturers of any productsor providers of any service mentioned in thisarticle.

References:

1.

Fletcher CD, Gustafson P, Rydholm A, etal: Clinicopathologic re-evaluation of 100 malignanthistiocytomas: Prognostic relevance ofsubclassification. J Clin Oncol 19:3045-3050,2001.

2.

Powell CM, Rosen PP: Adipase differentiationin cystosarcoma phyllades. A study of14 cases. Am J Surg Pathol 18:720-727, 1994.

3.

Fineberg S, Rosen PP: Cutaneousangiosarcoma and atypical vascular lesions ofthe skin and breast after radiation therapy forbreast carcinoma. Am J Clin Pathol 102:757-763, 1994.

4.

Sneige N, Yaziji H, Mandavilli SR, et al:Low-grade (fibromatosis-like) spindle cell carcinomaof the breast. Am J Surg Pathol25:1009-1016, 2001.

5.

Rosen PP: Review of "outside" pathologybefore treatment should be mandatory. AmJ Surg Pathol 26:1235-1246, 2002.