Praktische Probleme im Mammographie-Screening: Kolumnarzellläsionen einschließlich flache Epithelatypie und lobuläre Neoplasien

Der Pathologe (Impact Factor: 0.39). 01/2008; 29.

ABSTRACT Kolumnarzellläsionen (CCL) und lobuläre Neoplasien (LN) werden in Mammographie-Screening-Biopsien immer häufiger diagnostiziert. Der mammographische Leitbefund der CCL ist Mikrokalk (MK), LN sind meist Zufallsbefunde. Beide Läsionen – und speziell die flache Epithelatypie (FEA) als atypische Variante der CCL – sind häufig miteinander und auch mit einer atypischen duktalen Hyperplasie (ADH) assoziiert. Molekularpathologische Befunde von CCL zeigen chromosomale Veränderungen, die auch im duktalen Carcinoma in situ (DCIS) und in invasiven gut differenzierten Karzinomen gefunden werden. Dies unterstützt die Hypothese, dass CCL neoplastische Proliferationen sind. Klinische Befunde deuten darauf hin, dass CCL Indikatorläsionen und nichtobligate Präkanzerosen sind. Es gibt derzeit keine international einheitliche Klassifikation der CCL. Kennzeichnendes Merkmal der LN sind Mutationen im CDH1-(E-Cadherin-)Gen. Alternative genetische Veränderungen im CDH1-Pathway können in immunhistochemisch CDH1-positiven LN zu einem Funktionsverlust von CDH1 führen. Wir stellen die Hypothese auf, dass ein Teil der morphologischen und immunhistochemischen Hybridläsionen (WHO 2003) den LN mit alternativen CDH1-Funktionsverlusten entsprechen könnten. Neuere Verlaufsdaten weisen auf eine höhere Rate ipsilateraler Karzinome bei Patienten mit vorbekannter LN hin. Es ist eine offene Frage, ob die FEA und die LN eine gemeinsame Familie intralobulärer Neoplasien sind, die gemeinsame nichtobligate Vorläufer einer ,,low nuclear grade breast neoplasia family“ sind.

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    ABSTRACT: Because of advances in mammography and a concomitant rise in the number of breast biopsies being performed for mammographically detected abnormalities, increasing numbers of columnar cell lesions (CCLs) are being described by pathologists. However, these lesions can be challenging to manage, since their classification has changed over time and only limited research has been conducted regarding their clinical significance. CCLs may be characterized by a single layer of columnar cells (columnar cell change [CCC]), multiple layers with stratification and apical tufting (columnar cell hyperplasia [CCH]), or monomorphic cells with cytologic atypia (flat epithelial atypia [FEA]). The differentiation between CCC, CCH, and FEA is clinically significant: CCC and CCH are considered benign lesions, whereas FEA can be associated with, and even a precursor to, low-grade ductal carcinoma in situ and atypical ductal hyperplasia. Therefore, the identification of FEA at core biopsy should prompt excision of the remaining portion of the lesion.
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    ABSTRACT: The terminal duct-lobular unit is the origin of 2 distinct variants of intraepithelial neoplasia traditionally separated into ductal and lobular types based on a combination of cytologic and architectural features. In general, distinction of the fully developed or classic lobular intraepithelial neoplasia (LIN) from various grades of ductal intraepithelial neoplasia (DIN) is not a problem. An increasing number of lesions that appear to have intermediate, overlapping ductal and lobular features are being sent to us for consultation because of the distinctly different clinical implication of the 2 diagnoses. We have separated and designated these as MIN (mammary intraepithelial neoplasia, not otherwise specified), whereas others have categorized them into either a definitive ductal or lobular subtype. The recent findings that LIN lacks immunoreaction for E-cadherin coupled with significantly diminished to absent expression of the high molecular weight (HMW) cytokeratins in more than 90% of grade 1b or higher DIN prompted us to evaluate intraepithelial neoplasias for a possibly more precise immunohistochemical categorization. One hundred and ten examples of intraepithelial neoplasias, consisting of 40 classic LIN, 20 unequivocal DIN 1c to DIN 3 (ductal carcinoma in situ), and 50 MIN, were acquired from the files of the Armed Forces Institute of Pathology. These specimens were tested with an antibody to E-cadherin and with antibody 34ssE12 reactive against HMW cytokeratins 1, 5, 10 and 14. All samples of LIN showed complete absence of reactivity with anti-E-cadherin, whereas all cases of DIN displayed a positive immunoreaction. In contrast, the DIN lesions displayed little or no reactivity with 34ssE12, whereas the lobular lesions showed cytoplasmic reactivity, often in a distinct perinuclear pattern. Twenty-three of the morphologically indeterminate cases could be classified as either ductal or lobular based on the immunoprofile, and 27 demonstrated an immunoprofile that differed from either typical DIN or classic LIN. Among the 27 MIN, 11 were negative for both markers (negative hybrids), whereas 16 were positive for both markers (positive hybrids). These 2 antibodies in combination are extremely useful in distinguishing lobular and ductal lesions and clarifying the nature of some of the morphologically intermediate cases. Also, they have confirmed the presence of a group of intraepithelial lesions (MIN) with not only overlapping morphologic features, but also immunoprofiles distinctly different from either DIN or LIN. These MIN lesions may reflect either a transient stage in the development of DIN and LIN (the immediate post-stem cell stage) or a plastic group in transition from one type to the other. This group needs further evaluation for better understanding of its significance, pattern of progression, and behavior.
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