Papillary Carcinoma In Situ (Complex Sclerosing Papillary Lesion with Associated DCIS) Dr. Christopher Elston

Clinical History A female aged 59 years attended for routine breast screening. A lobulated 22 mm mass was found in the right upper outer quadrant; clinical assessment was 'probably benign'. Mammography and ultrasound examinations were designated 'indeterminate'. Ultrasound guided mammotome biopsy was performed. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Microscopic appearances The section shows several cores of tissue from a mass lesion composed mainly of well-formed papillary structures. These are lined by two-layered epithelium, with inner myoepithelial and outer secretory cells surrounding fibrovascular cores. The epithelial cells are regular in appearance with no nuclear atypia. Focally there is mild to moderate secretory cell proliferation. In addition, at the edge of the lesion in one core there are two duct spaces which contain a monotonous epithelial proliferation with a solid and partly cribriform architecture; some nuclear atypia is present in these cells and they exhibit a clear eosinophilic cytoplasm. Differential diagnosis Papillary lesions are classified under the following sub-headings:- Benign duct (or intracystic) papilloma a) solitary b) multiple Duct papilloma with epithelial atypia Papillary carcinoma in situ (encysted papillary carcinoma) Invasive papillary carcinoma In Europe non-operative needle core biopsies are reported using the following convention: B1 – normal B2 – benign B3 – benign of uncertain malignant potential B4 – suspicious of malignancy B5 – malignant It is clear that, depending on the morphological features present; papillary lesions can be allocated to any of the categories from B2 to B5. In this case the main lesion appears benign and it might be thought that the B2 category would be appropriate. However, focally there is moderate epithelial hyperplasia and the morphological features in the adjacent duct spaces raise the possibility of an associated in situ carcinoma; the choice then lies between B3 – benign of uncertain malignant potential and B 4 – suspicious of ductal carcinoma in situ. In most circumstances both categories would lead to further investigation, usually in the form of an excision biopsy; the difference is that a B3 diagnosis would result in a more limited diagnostic biopsy whilst a B4 diagnosis might be followed by a therapeutic excision, depending on the degree of suspicion clinically and on imaging. In view of this it was considered that the appropriate reporting category was: B3 – benign of uncertain malignant potential. Follow up An image-guided wire localisation biopsy was performed. The specimen weighs 56 gm and measures 85 x 40 x 35 mm. Centrally there is an ill-defined firm area approximately 15 mm in diameter with adjacent fat necrosis. Microscopically, the firm area consists of papillary structures, most of which show epithelial proliferation without atypia. In addition several ducts contain a monotonous proliferation of cells with vesicular nuclei showing moderate nuclear atypia and abundant eosinophilic cytoplasm, arranged in a cribriform architectural pattern; mitoses are scanty. These features are those of intermediate grade ductal carcinoma in situ (DCIS). Some papillary structures appear to have an intermediate epithelial proliferation with atypical cells similar to those found in the ducts involved by DCIS. The histological diagnosis is confirmed by immunostaining for basal (CK5, 14) and luminal (CK8/18) cytokeratins; a mixed cell population is seen in the papillary areas whilst in the cribriform structures the cell proliferation is dominantly of luminal type. A further feature is the presence of central sclerosis with entrapped ductules. These appearances are interpreted as those of a complex sclerosing papillary lesion with associated DCIS and are considered to be part of the spectrum of Papillary carcinoma in situ . No invasive element is seen. The closest excision margin was 2 mm (diagnostic excision only). Adjacent linear cellular fibrosis indicated the site of the previous mammotome biopsy. A cavity re-excision was performed and clear margins (>10 mm) were obtained. No further therapy was given and the patient remains well and tumour-free after two years clinical and imaging follow-up. Discussion A diagnosis of papillary lesion on needle core biopsy does not necessarily mean that excision is required. If the appearances are entirely benign (B2) and the core appears to be an adequate sample, based on the size of the core (multiple cores increase the yield) compared with the clinical and imaging features, there is evidence that no further surgery is required at this point. Follow-up should be maintained and if the lesion increases in size excision may then be advisable. Opinion is divided on the correct management of cases in which atypical features are found in a core biopsy, short of frank malignancy (B3), partly because most studies contain very few cases. Some have shown that the majority of lesions are subsequently shown to be papillary carcinoma in situ whilst others have found the opposite – the majority prove to be benign or atypical papillomas. In Nottingham it is our policy to recommend excision biopsy following a B3 diagnosis on core biopsy unless there are good clinical reasons to avoid surgery. Differential immunostaining with basal (CK5,14) and secretory (CK8,18) cytokeratins and myoepithelial markers (smooth muscle myosin (SMM), p63) may help to reduce the number of B3 diagnoses by recategorising cases as B2 or B5. Features which favour a malignant diagnosis include the following: multi-layering of epithelial cells the presence of nuclear atypia and an increase in mitotic figures a deficient myoepithelial layer (demonstrated by negative SMM and p63 immuno- staining) areas with a cribriform architecture a monomorphic epithelial growth pattern (supported by differential cytokeratin immuno-staining) NB care must be taken to avoid over-interpretation of entrapped epithelial structures in the peripheral pseudocapsule as evidence of invasion. A suspicious (B4) or malignant (B5) diagnosis on core biopsy requires therapeutic excision with clear margins or mastectomy. The type of definitive surgery depends on the clinical and imaging findings and patient choice. Papillary carcinoma in situ (Encysted Papillary Carcinoma) is regarded as a specific but uncommon variant of ductal carcinoma in situ (DCIS) occurring mainly in women over the age of 60 years. It is rare in symptomatic practice but may present as a soft palpable mass. The main method of detection is through mammographic screening in which it is visualised as an impalpable mass lesion, usually with associated cystic change. The presence of haemorrhage within such a cystic structure is highly suggestive of papillary carcinoma in situ. The appearance is that of a soft, circumscribed, cystic mass with a thin fibrous wall and a haemorrhagic or fleshy cut surface, approximately 10-30 mm in diameter. Microscopically there is a fundamental papillary structure with clear fibrovascular cores and sufficient epithelial proliferation with multilayering and cytological atypia to qualify as in situ carcinoma. A focal cribriform architecture is often present. If the diagnosis of malignancy is in doubt immunostaining should be carried out, as detailed above. Based on the degree of nuclear atypia and number of mitotic figures cases can be assigned to low, intermediate or high grade, in a similar way to DCIS. DCIS may be present in adjacent duct spaces and blocks should be selected carefully to include surrounding breast tissue and excision margins. Occasionally invasive carcinoma may intervene and the tumour periphery should be searched carefully for evidence of spread beyond the pseudocapsule; as noted above, however, the presence of entrapped epithelial islands within the pseudocapsule must not be interpreted as invasion. The prognosis of papillary carcinoma in situ is excellent and long-term survival (>10 years) is greater than 90%; this appears to be independent of grade. Mastectomy can be regarded as curative and conservation surgery also gives good results, especially if there is no DCIS in adjacent ducts (about 60% of cases). Local recurrence, both in situ and invasive, may occur if local excision is incomplete and this risk is related to the presence of adjacent DCIS. Final Diagnosis Papillary carcinoma in situ (complex sclerosing papillary lesion with associated DCIS) References Carder PJ, Garvican J, Haigh I, Liston JC. Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast. Histopathol 2005; 46: 320-327. Carter D. Intraductal papillary tumours of the breast. Cancer 1977; 39: 1689-1692. Ivan D, Selinko V, Sahin AA et al. Accuracy of core needle biopsy diagnosis in assessing papillary breast lesions: histologic predictors of malignancy. Mod Pathol 2004; 17: 165-171. Lefcowitz M, Lefcowitz W, Wargotz ES. Intraductal (intracystic) papillary carcinoma of the breast and its variants: a clinicopathological study of 77 cases. Hum Pathol 1994; 25: 802-809. Rosen EL, Bentley RC, Baker JA, Soo MS. Image-guided core biopsy of papillary lesions of the breast. Am J Radiol 2002; 179: 1185-1192. Shah VI, Flowers CI, Douglas-Jones AG et al. Immunohistochemistry increases the accuracy of diagnosis of benign papillary lesions in breast core needle biopsy specimens. Histopathol 2006; 48: 683-691.