Mammary intra-epithelial neoplasia

Terminology

	DIN 1a	intraduct hyperplasia, IDH
	DIN 1b	flat epithelial atypia
	DIN 1c	atypical intraduct hyperplasia and low grade DCIS
	DIN 2	grade 2 DCIS
	DIN 3	grade 3 DCIS

High molecular weight cytokeratins may be useful in distinguishing usual ductal hyperplasia from in situ carcinoma

		34bE12	CK5/6
	Usual ductal hyperplasia	+++3	+++3
	Atypical ductal hyperplasia	-/+3	-3
	Ductal carcinoma in situ	-/+3	-3
	Lobular carcinoma in situ	+++3	-3

Atypical ductal hyperplasia stains for pure epithelial cytokeratins (CK7, CK18, CK19), while usual interstitial hyperplasia shows a mix of luminal and basal cytokeratins (CK5/6, CK7, CK14, CK18, CK19)⁴. Atypical hyperplasia and DCIS express high levels of oestrogen receptors in nearly all cells, while usual epithelial hyperplasia shows heterogeneous expression⁴.

Differentiating ductal (DCIS, DIN) from lobular (LCIS, LIN) intra-epithelial mammary hyperplasia can usually be performed on H/E microscopy. However, some cases show an intermediate morphology, and may be designated as mammary intra-epithelial neoplasia (MIN). In particular, the solid variant of low grade DCIS (DIN 1c) may closely resemble CLIS. The combined e-cadherin and HMW cytokeratin immunoprofile may be useful in these cases. However, some cases also show a hybrid immunoprofile which differs from both classical lobular and classical ductal intra-epithelial neoplasia: further research is needed into such cases.

	e-cadherin- / 34ßE12+	e-cadherin+ / 34ßE12-	e-cadherin+ / 34ßE12+	e-cadherin- / 34ßE12-
classical lobular (LIN, all grades)	40/40 (Reactivity was distinctively finely granular, perinuclear and often polarised at one end of the nucleus. There was periluminal staining of intracytoplasmic lumina)1	0/401	0/401	0/401
classical ductal (DIN 1c to 3)	0/201	20/201	0/201	0/201
hybrid MIN	17/50 (classified on the basis of immunoprofile as lobular)1	6/50 (classified on the basis of immunoprofile as ductal)1	16/50 (classified on the basis of immunoprofile as hybrid)1	11/50 (classified on the basis of immunoprofile as hybrid)1

Optimum staining for 34ßE12 required a heat-retrieval method. Note that other studies have shown that low grade DIN 1a (intraduct hyperplasia, IDH) is immunoreactive for 34ßE12².

References

¹ Bratthauer, G. L., F. Moinfar, et al. (2002). "Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias." Hum Pathol 33(6): 620-7.

² Moinfar, F., Y. G. Man, et al. (1999). "Use of keratin 35betaE12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type--benign and malignant intraductal proliferations." Am J Surg Pathol 23(9): 1048-58.

³ Lerwill, M. F. (2004). "Current practical applications of diagnostic immunohistochemistry in breast pathology." Am J Surg Pathol 28(8): 1076-91.

⁴ Putti TC, Pinder SE, Elston CW, et al. Breast pathology practice: most common problems in a consultation service. Histopathology 2005; 47:445-57

This page last revised 17.9.2004.

©SMUHT/PW Bishop