22 February 2006 – Case of the Week #37


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We thank Dr. Lisa A. Cerilli, University of New Mexico Health Sciences, Albuquerque, New Mexico (USA), for contributing this case and the discussion.  We invite you to contribute a Case of the Week by sending an email to NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting.  We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case.  Please only send cases with a definitive diagnosis. 


Case of the Week #37


Clinical history


A 49 year old healthy woman underwent needle localization excision of a breast mass for biopsy proven low grade ductal carcinoma in situ.  A 9 mm lesion was identified histologically adjacent to, but not involved by, multifocal DCIS.  The epithelial component in the nodule showed the typical cytoarchitecture of fibroadenoma, but also had some atypical cells.  No mitotic figures were found.


Microscopic images:  image1, image2


What is your diagnosis? 


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Fibroadenoma with bizarre stromal giant cells (for this portion of the specimen)




The microscopic images show stromal cells with markedly enlarged and hyperchromatic, pleomorphic nuclei.  Many of the stromal cells showed multinucleated forms or prominent round, intranuclear pseudoinclusions.  The remaining breast showed foci of DCIS with low grade nuclear features, which of course was included within the final diagnosis.

Well-defined histological parameters typically are reliable indicators to differentiate benign from malignant entities.  The presence of enlarged and pleomorphic nuclei is classically regarded as a feature of malignancy, but may on occasion be evident in lesions with completely benign behavior.  This discordance between nuclear atypia and behavior is characteristically encountered in uterine leiomyomas (referred to as “symplastic” change), or schwannomas (described as “ancient change”).  Degenerative type atypia has also been described in osteoblastoma, chondromyxoid fibroma, fibrodysplasia, renal oncocytoma, stromal hyperplasia of the prostate, endometrial polyps, and salivary polymorphic adenoma (1-4), as well as in endocrine neoplasms.  Similar nuclear changes arising in mammary fibroadenomas are only seen rarely.


Architecturally, the overall pattern of fibroadenoma with bizarre stromal giant cells is that of the usual fibroadenoma, but with diffuse striking nucleomegaly of the stromal cells, accompanied by adequate cytoplasm.  Mitotic figures are notably absent.  Other neoplastic lesions in the breast that show atypical stromal cells include phyllodes tumor, sarcoma, and metaplastic breast carcinoma.   Distinction from these other lesions can be made by recognition of the lack of stromal overgrowth, cellular crowding and mitotic figures, and most importantly, the lack of crisp nuclear details (i.e. the chromatin is “smudgy”).  The presence of multinucleated giant cells in combination with mitotic activity, necrosis, stromal overgrowth or hypercellularity raises the question of another lesion, usually phyllodes tumor (5). The degree of atypia in fibroadenoma with bizarre stromal giant cells actually exceeds that which typifies malignant processes in the breast, another diagnostic clue.


Bizarre nuclear alteration in the presence of abundant cytoplasm may also be seen following external beam radiation therapy.  Due to radiation-induced inhibition of cell division, the nucleus becomes enlarged, acquiring bizarre features including pseudoinclusions.  Unlike radiation effect, fibroadenoma with bizarre stromal giant cells shows no epithelial or vascular abnormalities, the atypia is well-localized, and there is no history of radiation exposure.


Fibroadenoma with bizarre stromal cells is an uncommon benign entity in the breast which can be easily confused with phyllodes tumor or other lesions with malignant stromal cells, particularly in fine needle aspirations (6).  The bizarre nuclear changes are related to degenerative alterations, and they do not indicate aggressive or malignant behavior.  Treatment is conservative local excision, which is completely curative. 



1. Bahk WJ, Mirra JM.  Pseudoanaplastic tumors of bone.  Skeletal Radiol 2004; 33: 641-8.


2. Chang JH, Pathak AS, Dikranian AH, et al.  Benign prostatic stromal hyperplasia with bizarre nuclei.  J Urol 2003; 170:1951.


3. Tai LH, Tavassoli FA.  Endometrial polyps with atypical (bizarre) stromal cells. Am J Surg Pathol 2002; 26: 505-9.


4. Takeda Y.  An immunohistochemical study of bizarre neoplastic cells in pleomorphic adenoma: its cytological nature and proliferative activity.
Pathol Int. 1999;49:993-9


5. Tse GM, Law BK, Chan KF, et al.  Multinucleated stromal giant cells in mammary phyllodes tumors.  Pathology 2001; 33: 153-6.


6. Ng WK.  Fine Needle Aspiration Cytology of Fibroadenoma with Multinucleated Stromal Giant Cells.  Acta Cytol 2002; 46: 535-9.


Nat Pernick, M.D.
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