Invasive papillary carcinoma of the breast with an unusual immunophenotype

Abstract

To the Editor: Invasive papillary carcinoma (IPC) of the breast is extremely rare, and its clinicopathological characteristics are not well known. Due to a peculiar morphology that demonstrates papillary formation in the invasive elements, metastatic papillary adenocarcinoma should always be excluded. A case of IPC that showed an unusual immunoprofile is described, and the clinicopathological findings are highlighted. A 79-year-old woman presented with an irregular 9mm right breast mass detected incidentally on computed tomography (CT) performed for screening of liver function abnormality. She had no history of cancer but underwent total hysterectomy and opportunistic bilateral salpingectomy due to leiomyoma of the uterus 30 years earlier. On mammography, the lesion appeared as a mass with an indistinct contour including calcifications. Contrast-enhanced magnetic resonance imaging showed a well-enhanced mass with a benign pattern. Ultrasound-guided core needle biopsy (CNB) was performed. CNB sections demonstrated irregular gland-like nests that appeared to be papillary fronds projecting into lumens with no in situ lesion. Prominent lymphoplasmacytic infiltration was seen in the stroma. Epithelial cells constituting these nests showed a non-high nuclear grade. On immunohistochemistry, p63 and smooth muscle myosin heavy chain demonstrated an absence of myoepithelial cells around the irregular nests. As the lesion demonstrated unusual histologic pattern as primary breast carcinoma, to exclude possible metastasis from other organ, e.g., gynecological tract and lung, some immunohistochemical markers which had relatively high tissue specificity were stained. CK7 and androgen receptor showed positive staining, and GCDFP-15 and GATA-3 (Fig. 1a) demonstrated partial positive staining. The lesion was negative for estrogen receptor (ER), progesterone receptor, Her2, mammaglobin, TTF-1, Napsin A, WT-1, and PAX-8. Ki-67 showed only sparse positive staining. Taken together, the lesion was diagnosed as invasive carcinoma involving the right breast, but metastatic papillary carcinoma from other organs had to be excluded clinicoradiologically. To detect other primary sites, a systemic work-up including 18F-fluorodeoxy-glucose positron-emission tomography combined with CT was performed, but no other primary site was identified. Thus, lumpectomy and sentinel lymph node biopsy were performed as for primary breast cancer. On examination of the lumpectomy specimen, invasive elements showed a convoluted and anastomosed papillary structure (Fig. 1b, c). In addition, a solid focus composed of spindle cell compact proliferation with a streaming pattern was seen adjacent to the invasive component (Fig. 1d). On immunohistochemistry, ER-positive spindle cells were sparse (Fig. 1e). Spindle cells were positive for 34betaE-12 (Fig. 1f), CK5/6, and CK14 and scattered positive for smooth muscle actin (SMA). No synaptophysin or chromogranin-staining spindle cells were seen. This solid element was morphologically compatible with spindle+ cell ductal carcinoma in situ (DCIS), but its immunohistochemical findings were curious. In any case, since metastasis from another primary site was clinicoradiologically excluded, the case was in keeping with a primary breast IPC. A calcified hyalinized fibroadenoma was also identified adjacent to the invasive focus. The sentinel lymph nodes were negative for carcinoma. The patient was given only radiation therapy to the whole breast with no systemic therapy, neither chemotherapy nor endocrine therapy. In the past, it is likely that IPC was confused with infiltrative carcinoma without specific features associated with papillary in situ components. However, in the 4th edition of the World Health Organization (WHO) classification of breast tumours, IPC is defined as “invasive adenocarcinoma which has a predominantly papillary morphology (>90%) in the invasive component”. Invasive elements that have a frankly papillary configuration are extremely rare in breast cancer. The reported prevalence of IPC among all invasive breast cancers was 0.5% in some series, but it is fairly certain that the incidence of pure IPC is much lower according to the WHO 4th edition definition. The interesting point to note is that the present IPC case had unusual immunophenotype. Papillary breast carcinoma spans the spectrum of intraductal papillary carcinoma, encapsulated papillary carcinoma, solid papillary carcinoma, and invasive papillary carcinoma is almost exclusively ERpositive, but the lesion in the present case showed papillary invasive nests with ER negativity despite it being a non-high nuclear grade tumor. It is generally clear that ERnegative tumors are usually high nuclear grade. However,