Solid Papillary Carcinoma
Solid papillary carcinoma (SPC) is described in the 2012 WHO classification within the group of the intraductal papillary lesions and is defined as a variant of papillary carcinoma characterized by multiple solid nodules of neoplastic cells arranged around multiple fibrovascular spaces. Despite the lack of the external myoepithelial layer, these lesions are currently considered as noninvasive (Lakhani et al. 2012). However, cases of true invasive SPC exist.
SPC is a rare entity, accounting for 1–2% of breast carcinomas (BCs) (Otsuki et al. 2007).
It usually affects women in the seventh decade, with a mean age of 73.2 years (Maluf and Koerner 1995).
It is more frequently observed in female patients, but it has been sporadically described in men (Nassar et al. 2006).
SPC is typically unifocal and localized in the central region of the breast (Guo et al. 2016), although a single case of bilateral synchronous SPC has been reported in the literature (Yoshimura et al. 2013).
The clinical presentation does not differ from the other BC histological types, being usually diagnosed after the detection of a mammographic density or a palpable mass. In 20–25% of cases, a bloody nipple discharge may occur (Lakhani et al. 2012).
Mastectomy or conservative surgery represents the usual treatment for these tumors. However, since the risk of recurrence is not related to the surgical technique, mastectomy, as well as lymph node excision, seems to represent an overtreatment for small tumors with no signs of invasion (Guo et al. 2016). There is no agreement on the necessity of sentinel lymph node biopsy for these patients. Regarding adjuvant treatment, the benefit of radiation and hormone therapy is still debated.
SPCs present an excellent prognosis. Lymph node and distant metastasis are rare. Local recurrences have been reported, even if uncommon, and death for SPC should be considered exceptional (Guo et al. 2016). Recently, the 21-gene recurrence score (RS) multigene assay was performed in 5 cases of SPC, and the RS resulted low in 3 cases and intermediate in the remaining 2 cases, confirming the good prognosis of this histological type. The only woman who presented a local recurrence showed a RS of 25 (Turashvili et al. 2017).
SPCs may present foci of invasive carcinoma, frequently characterized by neuroendocrine or mucinous features (Nassar et al. 2006; Otsuki et al. 2007), even if other histotypes have been described. Invasive mucinous carcinomas associated with SPCs are usually classified as type B, characterized by high cellularity, lower mucin production, and neuroendocrine differentiation (Nassar et al. 2006) (chapter “Mucinous Carcinoma”).
Mixed cases, where SPC and encapsulated papillary carcinoma (EPC) (chapter “Encapsulated Papillary Carcinoma”) coexist, have been reported, hypothesizing a common carcinogenetic process for the two tumors (Cui and Wei 2015; Duprez et al. 2012).
Similarly to other papillary tumors, SPC is commonly classified as Luminal A type, showing an intensely positive expression of estrogen receptor (ER) and progesterone receptor (PR), lack of HER2 protein overexpression, and a low proliferation activity (Guo et al. 2016; Otsuki et al. 2007), and a similar immunohistochemical pattern is frequently reported also for the possibly associated invasive component (Nassar et al. 2006).
Nonetheless, the PAM50 gene signature applied on four cases of SPCs assigned them to the Luminal B subtype (Piscuoglio et al. 2014).
Myoepithelial markers, like p63 and high molecular weight cytokeratins (CK), may show positive or negative result by immunohistochemical staining (Ni and Tse 2016). Low molecular weight CKs, such as CK8 and CK18, are frequently positive (Lakhani et al. 2012).
Copy number aberration patterns are similar between papillary carcinomas (PCs) and ER+ invasive carcinomas of no special type (IC NST) of similar grade (Duprez et al. 2012). However, gene expression analysis showed a downregulation of genes related to cell migration, proliferation, assembly, and organization in PCs, whereas genes involved in cellular homeostasis and angiogenesis were upregulated (Piscuoglio et al. 2014).
Among the main types of PCs (SPC, EPC, and invasive papillary carcinoma), no differences in copy number aberrations were noted (Piscuoglio et al. 2014). On the other hand, SPC, when compared with EPC, presents a higher expression of neuroendocrine-related genes (e.g., RET, ASCL1, and DOK7), whereas EPC shows downregulation of genes involved in cell migration, possibly explaining the histological differences between these two entities (Piscuoglio et al. 2014).
Intraductal papilloma (chapter “Intraductal Papilloma”) and florid usual ductal hyperplasia (chapter “Usual Ductal Hyperplasia”) may present similar features with SPC, but they usually present no mitoses and do not show neuroendocrine or mucinous differentiation. Furthermore, in benign lesions, CK5/6 is usually intensely positive; therefore, its evaluation may be helpful in challenging cases (Lakhani et al. 2012; Rabban et al. 2006).
In case ER and/or PR expression are unusually weak or absent, metastatic neuroendocrine tumors to the breast should be taken into account, and the clinical history of the patient should be accurately reviewed in order to identify the primary malignancy (Burt et al. 2016).
References and Further Reading
- Lakhani, S. R., Ellis, I. O., Schnitt, S. J., Tan, P. H., van de Vijver, M. J. (2012). WHO classification of tumours of the breast. World Health Organization classification of tumours. Lyon, IARC press. ISBN-10: 9283224337.Google Scholar