Proposed Classification of Pathology of Human Mammary Gland


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Introduction

The pathology of the human breast is beset by redundant and confusing terminology. The classification offered herein is an attempt to simplify the nomenclature, based partly on subgross and histopathologic studies .of whole human breasts which permit the three dimensional recognition of geographically isolated lesions of hyperplastic, dysplastic, anaplastic and neoplastic character. An attempt has been made in the nomenclature to be non-commital about the site of origin (e.g. lobular versus ductal) of some structures or lesions since the evolution of these lesions might be interpreted in various ways by different observers. We believe the name given a lesion is not as important as long as everyone agrees to use the same name for the same pathologic entity.

The following classification is the one which we are using in our quantitative subgross studies correlated with conventional histopathology. Before studying the definitions and the slides, please note the following:

Part I of the manuscript (Part I - "Definitions of Normal Structures and Focal Lesions In the Human Mammary Gland") defines specific lesions in general terms. The abbreviation in parentheses after the name of each lesion is a code which we find convenient in our daily work. These abbreviations are used on the slide set for identification purposes.

Part II of the manuscript (Part II - "Captions for the Slide Set") consists of examples of most of the lesions defined in the first section. Note that we 'do not have examples of some less frequently encountered lesions (e.g. hyperplastic duct). Moreover, examples of the various kinds of infiltrating cancers are not included since these are not generally a problem of nomenclature. As in the definitions (Part 1) the abbreviations are those we use in our studies. Sometimes the abbreviation of the lesion is qualified by adding an abbreviation for a descriptive term when applicable. These are SCL for sclerosis, DIL for dilatation, and CALC for calcification.

The noun "lobule" has been specifically avoided for certain lesions designated herein as "terminal groupings of ducts and/or ductules". Although these structures are terminal, and lobule-like, we feel that some authorities might not wish to accept our belief that they are of lobular origin. It also seems unwise to try to apply, terms derived from traditional two dimensional histopathology, since such terms are not always accepted by everyone, and since the terms often have different meanings to different observers.

Hyperplastic lesions (e.g. HTG, HTD, HD, see definitions) are graded I, II, III, IV, and V for atypia on the basis of anaplastic characteristics. Any grade above IV is carcinoma-in-situ and is so designated. We have not attempted to grade the examples given, although we routinely do so in our own analyses.

The lesions selected for the slide set are the "purest" examples we could find. It should be pointed out that compound (mixed) lesions are frequently encountered.

The 35 mm slides in this set do not give as clear a representation of the three dimensional appearance as would study of the same subgross specimens by means of a dissecting microscope.

Sample slide label.

Sample slide label

 

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PART 1. Definitions of normal structures and focal lesions in the human mammary gland

Duct (D)
The system of epithelial-lined branching tubes which conducts secretions to the nipple. The largest ducts are located at and below the nipple. The smallest true ducts are the terminal ducts which enter the lobules. In the present classification, however, terminal ducts are designated separately because they are far more frequently the site of hyperplasia.

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Terminal Duct (TD)
The most distal terminal branch of the mammary duct system.
A terminal duct leads directly into a lobule, and an extralobular and intralobular portion of the terminal duct may be distinguished. This term is-also applied to the single duct which leads into the lesions we designate "terminal groupings of ducts and/or ductules", (TG) and "hyperplastic terminal groupings of ducts and/or ductules, types A and B (HTG-A and HTG-B) and which we interpret as lobular derivatives.

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Lobule (L)
A group of ductules and the intralobular portion of a terminal duct arranged In an ovoid formation, and possessed of its own distinctive areolar intralobular stroma.

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Ductule (DTL)
The smallest, blindly ending tubular epithelial structures that make up the resting mammary gland. They arise from the intralobular portion of a terminal duct. A group of ductules and the intralobular portion of the terminal duct comprise a lobule. The term ductule is reserved for the resting mammary gland. The terms acini or alveoli are reserved for the same or similar structures which show secretory activity in the prelactating and lactating gland.

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Alveoli or acini (A)
A term reserved for ductule-like terminal secretory units present in the prelactating and lactating mammary gland.

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Large Lobule (LL)
A lobule which is at least two times the size of background lobules, and the ductules of which are increased in number but without epithelial hyperplasia or cytological atypia. This definition is arbitrary audit is suggested that large lobules maybe one extreme of a bell-shaped curve of lobule size, and not a clearly separate class in regard to size. Large lobules may show one or more of the following: secretory activity (SEC), dilatation of ductules (DIL), chronic inflammatory infiltration (INF), sclerosis (SCL), and calcification (CALC).

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Persistent Lobule (PL)
A well developed lobule which persists in an otherwise atrophic (usually postmenopausal) breast In which most lobules have either vanished or are severely atrophic. Persistant lobules may show secretory activity (SEC), dilatation of ductules (DIL), chronic inflammatory infiltration (INF),sclerosis (SCL), and calcification (CALC). Persistent lobules are morphologically Identical to normally sized or large lobule, but are recognized because they are conspicuously different from the surrounding atrophic background.

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Hypersecretory Lobule (HSL)
A lobule, often larger than most background lobules, which shows apical secretory vacuoles in the epithelial cells and acidophilic and vacuolated secretion in the lumen.

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Sclerosing Adenosis (SA)
A lobule, or a group of confluent lobules, which show increased stromal connective tissue and some disarray and/or proliferation of ductules. Sometimes there is a central fibrous core with surrounding enlarged ductules which radiate outward, giving the entire formation a "cockle burr" appearance.

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Apocrine Cyst(s) (APO CYST)
A lobule in which one or more, but usually all ductules are cystically enlarged, showing "apocrine metaplasia" of the epithelial lining. The lining epithelium usually forms small discrete papillary projections of variable number into the lumen. The attached terminal duct is rarely seen.

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Epithelial Cyst (EP CYST)
A spherical cyst lined by a single layer of flattened to cuboidal epithelium. The content is generally homogeneous or granular, eosinophilic material.

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Stromal Cyst (S CYST)
A spherical cyst not lined by epithelium, but by dense stromal connective tissue (these may be old epithelial cysts the lining of which has degenerated and disappeared). The content of stromal cysts is generally eosinophilic, proteinaceous material with or without granules and calcifications.

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Terminal Grouping of Small Ducts and/or Ductules (TG)
A small terminating lobule-like formation at the end of, or attached to the side of a small duct. The blindly ending epithelial-lined units are .fewer in number than the ductules of normal lobules, and are often arranged in a flattened fern-like or spreading pattern. The stroma is often that of mature lobules in the resting breast. Variable degrees of cytological atypia, usually slight, may be observed. We believe that at least some of these lesions may be early or arrested stages of lobule formation.

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Hyperplastic Terminal Grouping of Small Ducts and/or Ductules, Type A (HTG-A)
A hyperplastic lobule-like grouping of blindly ending small ducts or ductules. The epithelial-lined subunits (i.e. ducts and/or ductules) are fewer in number and much larger (four times or more) than are nondilated ductules of normal lobules. When greater amounts of hyperplasia are present, the epithelial proliferations occupy more of the intraluminal space of each subunit. Those subunits which are completely or nearly completely filled with epithelial cells are often the size of small mammary ducts. Generally speaking, those epithelial-lined subunits which have pleomorphic and sometimes pyknotic nuclei are judged less atypical (lower grade) than those subunits which have more uniform nuclei surrounding false glandular spaces, as "pearls on a string". The more atypical epithelial populations merge imperceptibly by a series of transitions into carcinoma-in-situ of the ductal type. HTG-A are often contiguous with a cytologically similar hyperplastic lesion in the distal part of the attending terminal duct, suggesting a common origin in the terminal grouping and the terminal duct, or in both. We believe that HTG-A is a type of hyperplastic lobule and that the small subunits of which it is composed are in truth hyperplastic ductules.

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Hyperplastic Terminal Grouping of Small Ducts and/or Ductules, Type (HTG-B)
Another type of hyperplastic lobule-like grouping of blindly-ending small ducts or ductules. The terminal epithelial-lined subunits (ducts and/or ductules) are about as numerous as are the ductules of normal lobules. In the smallest lesions the terminal subunits are the size of normal ductules. The subunits which have the most hyperplasia may be enlarged up to five times the size of normal ductules. The central lumen of each .terminal subunit is small and the larger subunits are filled with epithelial cells. The cytological atypia grades into carcinoma-in-situ of the lobular type. We believe that this lesion is a kind of hyperplastic lobule and the terminal subunits are hyperplastic ductules. We have never observed HTG-B's to be associated with papillary lesions in the terminal duct, as is often true in the case of HTG-A's.

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Hyperplastic Terminal Duct (HTD)
Hyperplasia of epithelium of extralobular and/or intralobular terminal duct. The duct is usually enlarged due to distension by the proliferating epithelial cells which form papillary, solid or cribriform patterns. The epithelial cells show variable amounts of cytological atypia from slight to an appearance approaching carcinoma-in-situ of the classic ductal type. Many hyperplastic terminal ducts are contiguous with a hyperplastic lobule, appearing to form a single lesion of the "terminal ductal-lobular unit". The terminal duct may persist after lobular atrophy occurs.

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Hyperplastic Duct (HD)
Hyperplasia of epithelium of duct other than terminal duct, showing variable degrees of cytological atypia from slight to an appearance approaching carcinoma-in-situ. This lesion is seldom observed and we do not have an example.

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Carcinoma-in-situ, Ductal Type (DCIS)
Intraepithelial carcinoma with the cytological characteristics of ductal carcinoma-in-situ, usually arising in terminal ducts and their lobules but occasionally seen arising focally in larger ducts or preterminal ducts.

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Carcinoma-in-situ, Lobular Type (LCIS)
Intraepithelial carcinoma with the cytological characteristics of lobular-carcinoma-in-situ and located in lobules and possibly also in the intralobular portion of the terminal duct.

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Fibroadenoma (FA)
A circumscribed, generally ovoid grouping of ductules supported by mucoid to dense connective tissue. Both intra-canalicular and pericanalicular formations are observed. The smallest lesions show morphological evidence of lobular origin.

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Duct papilloma (D-PAP)
A papilloma with variable epithelial atypia located within a duct proximal to the Intralobular and extralobular parts of terminal ducts. The degree of atypia varies from slight to an appearance which rarely approaches carcinoma-in-situ. Intraductal papillomas generally have well developed connective tissue stalks in contrast to the papillary epithelial hyperplasia sometimes observed in terminal ducts and in hyperpiastic lobules.

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Scirrous Carcinoma (CA-SCIR)
Invasive mammary carcinoma with a predominating pattern of small nests of epithelial cells in a relatively abundant fibrous stroma.

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Mucoid (Colloid) Carcinoma (CA-COL)
Invasive mammary carcinoma with a 'predominate pattern of nests of cancer cells floating in pools of mucoid material.

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Papillary Carcinoma (CA-PAP)
Invasive mammary carcinoma with a predominately papillary pattern.

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Medullary Carcinoma (CA-MED)
Invasive mammary carcinoma with a predominately cellular (medullary) pattern, with or without lymphoid stroma.

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Compound Lesions
Mixed lesions combining the features of preceding lesions. Compound lesions are frequent, and essentially any combination is possible. These lesions are often confusing and their exact evolution may be impossible to trace.

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