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Cystic hypersecretory hyperplasia is a rare histologic change. Its significance is still unclear but it is important to identify these histologic changes because of its resemblance to ductal carcinoma in situ.


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Cancer 1988;61:1611-1620
Dilated cysts lined by orderly, flat columnar epithelial cells with eosinophilic cytoplasm and round to oval vesicular cytologically benign nuclei and filled with homogenous, eosinophilic, colloid-like material


Pregnancy-like (Pseudolactational) Hyperplasia: A Primary Diagnosis in Mammographically Detected Lesions of the Breast and Its Relationship to Cystic Hypersecretory Hyperplasia

Sandra J. Shin, M.D.; Paul Peter Rosen, M.D.

From the Department of Pathology, New York Presbyterian Hospital– Weill Medical College of Cornell University, New York, New York, U.S.A.

Am J Surg Pathol 2000;24:1670-1674 Abstract quote

Pregnancy-like (pseudolactational) hyperplasia (PLH) has long been recognized as an incidental finding in breast biopsies performed for various clinically detected benign and malignant conditions. The histologic features of PLH have been well described, including some instances exhibiting cytologic and structural atypia. The presence of calcifications in these lesions was rarely mentioned and was considered to be of little consequence. More recently, however, calcifications in PLH have become the target of needle localization and needle core biopsies.

The authors report 12 instances in which PLH was the primary diagnosis in biopsy specimens obtained for radiographic abnormalities, usually calcifications. Six of 12 procedures (50.0%) were performed for mammographically detected calcifications, four cases for a mass, one for an ``abnormal mammogram,'' and one for galactorrhea. Calcifications were present in PLH in 10 biopsies, in benign terminal ducts in one specimen, and were not identified histologically in the remaining specimen. In most instances, calcifications associated with PLH had smooth round or lobulated contours and distinctive, internal, unevenly spaced laminations. Cystic hypersecretory hyperplasia (CHH) was present in five specimens. In four of the five specimens, CHH merged with PLH (PLH/CHH). Four of 12 specimens (33.3%) showed atypia within foci of PLH/CHH. PLH should be recognized as a primary diagnosis in breast biopsies for mammographically detected abnormalities such as calcifications. Some calcifications associated with PLH have a distinctive histologic appearance, and their recognition can aid in the diagnosis of PLH.

Additional cases of PLH/CHH must be studied to ascertain the clinical significance, if any, of this previously undescribed entity. The precancerous significance of PLH/CHH and of PLH with atypia has not been determined. In most instances, surgical excision would be prudent if PLH/CHH or PLH with atypia is present in a needle core biopsy specimen.




Lobulocentricity of breast hypersecretory hyperplasia with cytologic atypia: infrequent association with carcinoma in situ.

Kasami M, Jensen RA, Simpson JF, Page DL.

Departments of Pathology, Shizuoka Cancer Center, Shizuoka (formerly at Nagoya National Hospital, Nagoya), Japan.
Am J Clin Pathol. 2004 Nov;122(5):714-20. Abstract quote  

Intracytoplasmic and extracytoplasmic features of secretion, similar to lactational changes, occasionally are seen in the nonparous human breast, usually are lobulocentric, and often have aberrant cytologic and nuclear changes. In these "hypersecretory hyperplasias" (HHs; 38 women) there is bubbly cytoplasm with irregular apical cytoplasmic and/or nuclear protrusions.

In a review of 138 HH cases the following additional associated changes were found: nuclear atypia (HHA, 22 women), atypical ductal hyperplasia (ADH-HH, 24 women), and ductal carcinoma in situ (DCIS-HH, 54 women). A diagnosis of DCIS-HH requires involvement of true duct(s) and of several contiguous lobular units, emphasizing the importance of extent and overall size and similar cytology and histologic arrangement of intercellular spaces indicating a homogeneous cell population. Cases of HH regularly are characterized as having adjacent and nearby lobular units with quite diverse cytologic patterns.

The major impact of this study is to recognize that HHA may be regarded as having uncertain significance when found alone in the usual presentation in a single unit, but that formally defined ADH and/or DCIS may be locally present.
Carcinoma arising from preexisting pregnancy-like and cystic hypersecretory hyperplasia lesions of the breast: a clinicopathologic study of 9 patients.

Shin SJ, Rosen PP.

Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Am J Surg Pathol. 2004 Jun;28(6):789-93. Abstract quote  

The intimate histologic relationship of pregnancy-like hyperplasia (PLH) and cystic hypersecretory hyperplasia (CHH) has been previously reported. However, none of these published cases contained coexisting carcinoma.

In this study, we describe 9 additional cases of this lesion, all of which also revealed ductal carcinoma in situ (DCIS) as well as invasive carcinoma in 1 case. Hematoxylin and eosin-stained slides were reviewed for all cases.

All were women who ranged in age from 35 to 49 years (mean 42.0 years; median 42.5 years). Reasons for surgical biopsy were calcifications in 6, breast mass in 2, and nipple discharge in 1. One patient with a mass also experienced nipple discharge. Three women initially underwent needle core biopsy and 6 had an excisional biopsy. Six women ultimately had mastectomies.

Histologically, 5 had CHH merging with coexisting PLH. Atypia was seen in one or both components. All 9 cases contained DCIS. Two cases showed micropapillary DCIS, one of which appeared to arise from atypical PLH, while 4 of the 7 cases containing cystic hypersecretory DCIS appeared to arise from coexisting atypical CHH. Well-differentiated invasive carcinoma was identified in 1 case adjacent to cystic hypersecretory DCIS. Subsequent sentinel lymph node biopsy in this case revealed micrometastatic disease. Clinical follow-up was obtained in 9 patients and ranged from 10 to 69 months. All patients were free of disease at the time of last follow-up.

Careful clinical follow-up is recommended for lesions that display atypia in PLH, CHH, or a histologically combined lesion. If these lesions are found on a needle core biopsy specimen, an excisional biopsy is recommended. DCIS, usually micropapillary or cystic hypersecretory types, and rarely invasive carcinoma can arise in this setting. Affected patients are typically younger than those with more common types of breast carcinoma.

Cystic hypersecretory hyperplasia and cystic hypersecretory duct carcinoma of the breast. Pathology, therapy, and follow-up of 39 patients.

Guerry P, Erlandson RA, Rosen PP.

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

Cancer 1988 Apr 15;61(8):1611-20 Abstract quote

The study documented in this article was performed to define the clinical and morphologic features of cystic hypersecretory carcinoma (CHC) and cystic hypersecretory hyperplasia (CHH) of the breast. Both lesions are characterized by the formation of cystically dilated ducts containing a homogeneous eosinophilic secretion that resembles thyroid colloid.

In most cases CHC features micropapillary intraductal carcinoma, occasionally giving rise to a high-grade, invasive carcinoma that is absent from CHH. Electron microscopy of the cystic component in one case of CHC showed ultrastructural characteristics of metabolically active cells, but few secretory granules.

Twenty-nine patients with CHC were observed for up to 23 years. Twenty-five women who had intraductal carcinoma were well or died of other causes. Of the four patients who had invasive carcinoma, one died 9 months after being diagnosed as having systemic metastases, and the other three remained disease-free. Ten cases of CHH were reviewed; follow-up information was available for eight patients for up to 5 years. Six women were alive and well. One woman died of contralateral invasive carcinoma, and a second was well having had a modified radical mastectomy for a separate, coexisting intraductal carcinoma in the same breast.

These findings indicate that intraductal CHC has the same low-grade clinical course as other forms of intraductal carcinoma. Because invasive carcinoma arising in this setting appears to be histologically high-grade, it is important to recognize and promptly treat the lesion while still in its in situ phase. Foci with the appearance of CHH may be found in CHC, but in this study progression from CHH to CHC was not observed. A thorough histological examination is needed to distinguish between CHC and CHH.

Lesions judged to be CHH are adequately treated by wide excision. Additional long-term, follow-up studies will be necessary to define the precancerous potential of CHH.

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Last Updated November 8, 2004

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