Cystic Hypersecretory Hyperplasia Research Articles

Atypical cystic hypersecretory lesions of the breast commonly harbour TP53 alterations.

Cystic hypersecretory lesions are rare and include atypical cystic hypersecretory hyperplasia (A-CHH) and cystic hypersecretory carcinoma in situ (CHC-IS). Despite detailed morphological descriptions, little is known about the genetic landscape of these lesions. We identified four A-CHH and three CHC-IS from 2010 to 2022. Patients ranged from 39 to 65 (median 49) years. All lesions showed characteristic cystically dilated ducts with colloid-like secretions lined by enlarged cells with hyperchromatic nuclei and at least moderate cytological atypia. CHC-IS was remarkable for a greater degree of intraductal proliferation, typically with a micropapillary pattern. Four patients had concurrent ipsilateral invasive carcinoma. Next-generation sequencing (104 cancer-associated genes) was successful in four, showing variants in TP53 (3), KEAP1 (1) and MDM2 (1). p53 immunohistochemistry was concordant with molecular results with mutant-pattern staining in three TP53-mutants and wild-type in one. In three cases where sequencing failed, one showed mutant p53 staining, one was wild-type and one had no remaining lesion. The combined molecular and immunohistochemical results demonstrated p53 alterations in one A-CHH and three CHC-IS. Based on this limited cohort, atypical cystic hypersecretory lesions appear to commonly harbour TP53 alterations. To our knowledge, this is the first study to characterise molecular alterations in this rare subset of breast lesions.

Cystic Hypersecretory Carcinoma of the Breast: A Rare Case Report with Review of Literature and Emphasis on Differential Diagnosis.

Karthik DhandapanCystic hypersecretory carcinoma (CHC) is a rare subset of in-situ breast carcinoma with or without associated invasive carcinoma. It is part of a spectrum of cystic hypersecretory lesions that includes cystic hypersecretory hyperplasia (CHH), CHH with atypia, CHC in situ, and CHC with invasion. Only 20 cases of CHC with invasion have been reported so far. A 60-year-old female presented with a palpable right breast mass. A core needle biopsy was carried out, which was reported as invasive breast carcinoma with areas of ductal carcinoma in situ (DCIS). Modified radical mastectomy was done post-neo-adjuvant chemotherapy; On microscopy, dilated cystic spaces filled with eosinophilic secretions (thyroid colloid-like), lining neoplastic cells with variable degrees of proliferation and atypia were seen. There were multiple foci of invasion; both skin invasion and axillary lymph node metastasis were present. Immunohistochemistry (IHC) was done with relevant markers; correlating all these findings, a diagnosis of CHC with invasion was made. CHC is a distinct form of DCIS with or without associated invasion. Awareness of this entity is required to rule out other differential diagnoses and to avoid misinterpretation. Little is known about the IHC profile, biological behavior, prognosis, and molecular profile of CHC due to its rarity.

Invasive cystic hypersecretory carcinoma of the breast: a rare variant of breast cancer: a case report and review of the literature

BackgroundCystic hypersecretory carcinoma is a rare subtype of breast cancer. It is a member of cystic hypersecretory lesions, which include a series of pathological disease lineages: cystic hypersecretory hyperplasia (CHH), CHH with atypia, cystic hypersecretory carcinoma (CHC) and invasive CHC. It was found that most cystic hypersecretion lesions were in situ carcinoma, and only 19 cases of invasive cystic hypersecretion carcinoma were reported.Case presentationWe are reporting a case of a 63-year-old female who had a lump in her left breast for 3 years. A modified radical mastectomy was done and morphological diagnosis of invasive CHC with axillary node metastasis was made.ConclusionsOwing to a smaller number of reported cases, little is known about the biological behavior, prognosis and molecular study of cystic hypersecretion lesions. Therefore, more cases with follow-up data are needed to reveal the biological behavior of this rare tumor.

Cystic Hypersecretory Hyperplasia of Breast

Cystic Hypersecretory Hyperplasia of Breast

Pathologic Spectrum of Secretory and Mucinous Breast Lesions

-The morphologic spectrum of secretory breast lesions encompasses benign, borderline, and malignant lesions. They are characterized by luminal pink, proteinaceous secretions and variable degrees of cytologic atypia ranging from low grade to high grade, with frequent papillary formations. Other lesions, benign and malignant, can also show luminal and extraluminal secretions and share similar features with secretory lesions, making them diagnostically challenging. -To discuss the differential diagnosis of secretory breast lesions, emphasizing the most important diagnostic features of benign and malignant lesions. Lesions with intraluminal secretions discussed at length in this review include pregnancy-like hyperplasia, cystic hypersecretory hyperplasia, collagenous spherulosis, microglandular adenosis, hypersecretory carcinoma, and secretory carcinoma. Lesions with extravasated mucin, such as mucocele-like lesions and mucinous carcinoma, are also briefly discussed. -Published articles obtained from a PubMed search of the English literature were the primary source for this review. -Lesions with secretory features described in this review show a pathologic spectrum, sometimes even within the same lesion. As a consequence, one should employ a low threshold for recommending reexcision on a core biopsy containing benign-appearing hypersecretory glands and use all ancillary data, including clinical presentation, imaging findings, morphology, immunohistochemistry, and molecular pathology, to render a final diagnosis.

Clinicopathologic features of cystic hypersecretory lesion of the breast

To study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast. Clinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed. All six patients were female, age ranged from 37 to 71 years (average 49.3 years). Three cases were cystic hypersecretory hyperplasia (CHH), the other three cases were cystic hypersecretory carcinoma (CHC). Clinically the lesions presented as either breast mass or mammographic calcification.Grossly, the cystic hypersecretory lesions were poorly circumscribed, with multiple colloid containing cysts on the cut surface. Microscopically, the remarkable feature was numerous enlarged cysts which contained densely eosinophilic homogeneous secretion similar to the colloid seen in thyroid follicles, and calcification was seen in the cyst in one case. The secretion was D-PAS and mucicarmine positive. The lining epithelium of the cysts was uniformly flat, cuboid or columnar, and arranged in a monolayer. The cells may be arranged in turfs, solid or micropapillary patterns in CHH.In cases with dysplasia, the epithelium showed cytological and structural atypia, but the usual morphology of atypical dutal hyperplasia such as arcades, rigid bridges or cribriform pattern was less common. The three CHC included two invasive ductal carcinomas (IDC) and one ductal carcinoma in situ (DCIS).In CHL, there was immunoreactivity to S-100 protein, CK5/6 and CK14.Of the three CHCs, ER and PR were expressed in only one IDC.No HER2 expression was identified in the two invasive CHCs.One patient was lost to follow-up, and the rest were uneventful at 18 months. CHL of the breast is a rare pathological entity. Multiple colloid-filled cysts is a unique histological feature. The epithelium of CHL may show usual hyperplasia, dysplasia or carcinoma.

Cystic Hypersecretory (In Situ) Carcinoma of the Breast

Cystic hypersecretory carcinoma (CHC) is an uncommon variant of ductal carcinoma in situ characterized by, among other features, the presence of luminal secretion resembling thyroidal colloid. CHC is thought to behave in an indolent manner but has the potential to give rise to invasive carcinoma, which is often poorly differentiated. We studied the immunohistochemical, clinical, and morphologic features of 10 cases of CHC. All patients were women averaging 62.8 years in age (range, 47 to 79 y). The clinical/radiographic presentation was a mass (5/10), calcifications (3/10), bloody nipple discharge (1/10), and unknown (1/10). Microscopic size of CHC ranged from 0.2 to 2.7 cm (mean, 0.9 cm). Micropapillary growth was present in all cases. Nuclear grade was intermediate (5/10) or high (5/10). One case also showed microinvasive carcinoma. All cases arose in a background of cystic hypersecretory hyperplasia (CHH) and/or CHH with atypia. CHC was ER in 8/10 cases (ER+/PR+, 4/10; ER+/PR+, 4/10). Two cases were ER-/PR-, including the case with microinvasive carcinoma. All were HER2-. Androgen receptor was expressed in 3/10 (30%) cases. Myoepithelial stains p63, smooth muscle myosin, and CK5 showed circumferential staining in 9/10 (90%) cases, whereas 1 case was negative for p63, smooth muscle myosin, and CK5 in both CHC and adjacent CHH. Basal-like carcinoma markers EGFR, CK14, and CK5 were negative in all cases, with the exception of 1 case that was positive for EGFR. Four patients with follow-up information showed no evidence of disease (mean, 5.5 y). CHC is a distinct variant of ductal carcinoma in situ that arises in a background of CHH and is characterized by micropapillary growth, intermediate-grade to high-grade nuclei, and luminal colloid-like secretion. CHC is usually ER and HER2-. Negative or discontinuous reactivity with myoepithelial markers may be seen, despite its in situ nature. CHC usually behaves in a nonaggressive manner as was seen in our patients who were all free from disease at last follow-up.

Cystic hypersecretory carcinoma with microinvasive carcinoma and cystic hypersecretory hyperplasia of breast: report of a case

患者女,44岁.发现左侧乳腺肿物,行肿物切除术,原单位冷冻切片病理报告导管原位癌伴浸润,遂行乳腺改良根治术.于2009年4月7日来本院会诊.具体病史不详.病理检查:镜下观察:肿瘤主要由含有大量均质嗜酸性分泌物的大小不等扩张的腺腔构成,形态酷似甲状腺滤泡.病变广泛,部分腺腔被覆单层扁平上皮,形态温和。

Carcinoma arising from preexisting pregnancy-like and cystic hypersecretory hyperplasia lesions of the breast: a clinicopathologic study of 9 patients.

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.

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

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.

Cystic Hypersecretory Duct Carcinoma of the Breast:A Case Reprot Describing the Cytologic Features.

We report the clinical, cytological and pathological features of so-called cystic hypersecretory duct carcinoma occurring in a 60-year-old Japanese woman. The tumor mainfested a multicystic mass ultrasonographically, and aspiration biopsy cytology revealed atypical ductal epithelial cells with vacuolar cytoplasm. A modified radical mastectomy was performed. Histologically, the lesion was charcterized by many dilated ducts containing eosinophilic secretions, which resembled thyroid colloid. The ducts were lined by an intraductal micropapillary carcinoma with hobnail-shaped cells, and were positive for lactalbumin immunohistochemically. Additionally, a so-called cystic hypersecretory hyperplasia was seen in the surrounding breast parenchyma. Although a direct transition from the hyperplasia to the carcinoma was not proved, a close relationship between the two lesions was suggested.

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

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.

Cystic hypersecretory duct carcinoma of the breast

This report describes a grossly and microscopically distinctive multicystic form of duct carcinoma of the breast which we have termed cystic hypersecretory duct carcinoma. The outstanding morphologic feature is marked secretory activity with the formation of dilated ducts and cysts containing homogeneous, eosinophilic material which resembles thyroid colloid. The inconspicuous epithelium lining the cysts gives rise to micropapillary carcinoma which also occurs in associated ducts. A biopsy that consists entirely of cystic elements, lacking the papillary component, should be termed cystic hypersecretory hyperplasia rather than carcinoma. This may be a persistent condition with the potential to evolve into carcinoma. Eight patients with cystic hypersecretory duct carcinoma were studied, ranging in age from 32 to 78 years (mean 54). In two cases there was coexistent invasive carcinoma, presenting as inflammatory carcinoma with bone metastases in one woman and with a single axillary lymph node metastasis in another. Six patients with intraductal carcinoma treated with mastectomy or local excision have remained well, the longest follow-up being 2 years. Histochemical studies were negative for thyroglobulin in all cases studied. Some lesions were positive for one or more of the following: mucin by mucicarmine stain; carcinoembryonic antigen; alpha-lactalbumin; mouse mammary tumor virus GP52 antigen. Cystic hypersecretory duct carcinoma is morphologically distinguishable from juvenile (secretory) carcinoma and from mucinous (colloid) carcinoma. Longer follow-up and study of additional cases will be necessary to determine if this lesion has distinctive clinical characteristics.