Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Solid Papillary Carcinoma

  • Elena Vissio
  • Caterina Marchiò
  • Anna SapinoEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4760-1

Synonyms

Definition

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.

Clinical Features

  • Incidence

    SPC is a rare entity, accounting for 1–2% of breast carcinomas (BCs) (Otsuki et al. 2007).

  • Age

    It usually affects women in the seventh decade, with a mean age of 73.2 years (Maluf and Koerner 1995).

  • Sex

    It is more frequently observed in female patients, but it has been sporadically described in men (Nassar et al. 2006).

  • Side

    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).

  • Clinical presentation

    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).

  • Treatment

    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.

  • Outcome

    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).

    When SPCs are associated to an invasive carcinoma, the outcome is related to the features of the infiltrative component (Lakhani et al. 2012; Tan et al. 2016).

Macroscopy

At macroscopic examination, SPC usually appears as a well-circumscribed lobulated mass, characterized by a whitish-gray or yellowish-brown color (Lakhani et al. 2012). The size may be variable, with a reported average diameter of 2.5 cm (Guo et al. 2016).

Microscopy

At low magnification, SPC is characterized by multiple cellular nodules. Although its borders appear well defined, the myoepithelial peripheral layer is frequently absent at immunohistochemical analyses (Fig. 1a, b). To date, it is still debated if SPC should be considered as a low-grade invasive carcinoma or a variant of ductal carcinoma in situ “DCIS” chapter. Nonetheless, because of their generally favorable clinical course, the current WHO classification recommends to consider SPCs as in situ lesions (Lakhani et al. 2012). By contrast, irregular margins and multiple small nests arranged in a jigsaw pattern represent typical features that suggest invasive growth (Lakhani et al. 2012).
Fig. 1

(a) Solid papillary carcinoma is characterized by a dense neoplastic proliferation featuring well-defined borders (H&E); (b) calponin immunohistochemical reaction shows focal lack of myoepithelial peripheral cell layer

Inside the nodules, neoplastic cells are densely organized. They may form typical peripheral palisading around delicate fibrovascular structures (Fig. 2a). Cells usually present small dimensions, hyperchromatic nuclei, granular cytoplasmic pattern, and occasionally spindle cell features (Lakhani et al. 2012). They are generally low- or intermediate-grade lesions, with low mitotic activity (Guo et al. 2016). SPC may produce extracellular and/or intracellular mucin (Wei 2016), and neuroendocrine differentiation is reported in about half of cases (Fig. 2b) (Otsuki et al. 2007).
Fig. 2

(a) Densely organized neoplastic cells form a peripheral palisading layer around delicate fibrovascular structures (H&E). (b) SPCs may show neuroendocrine differentiation (immunohistochemical reaction with anti-synaptophysin antibody)

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).

Immunophenotype

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).

Synaptophysin (Fig. 2b) and/or chromogranin, considered typical neuroendocrine markers, is expressed in more than 50% of cases (Guo et al. 2016; Lakhani et al. 2012; Otsuki et al. 2007).

Molecular Features

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).

Differential Diagnosis

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

  1. Burt, M., Madan, R., & Fan, F. (2016). Metastatic gastrinoma in the breast mimicking primary solid papillary carcinoma. Human Pathology, 56, 143–146.CrossRefGoogle Scholar
  2. Cui, X., & Wei, S. (2015). Composite encapsulated papillary carcinoma and solid papillary carcinoma. Pathology International, 65, 133–137.CrossRefGoogle Scholar
  3. Duprez, R., Wilkerson, P. M., Lacroix-Triki, M., Lambros, M. B., MacKay, A., A’Hern, R., Gauthier, A., et al. (2012). Immunophenotypic and genomic characterization of papillary carcinomas of the breast. The Journal of Pathology, 226, 427–441.CrossRefGoogle Scholar
  4. Guo, S., Wang, Y., Rohr, J., Fan, C., Li, Q., Li, X., & Wang, Z. (2016). Solid papillary carcinoma of the breast: A special entity needs to be distinguished from conventional invasive carcinoma avoiding over-treatment. The Breast, 26, 67–72.CrossRefGoogle Scholar
  5. 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
  6. Maluf, H. M., & Koerner, F. C. (1995). Solid papillary carcinoma of the breast. A form of intraductal carcinoma with endocrine differentiation frequently associated with mucinous carcinoma. The American Journal of Surgical Pathology, 19, 1237–1244.CrossRefGoogle Scholar
  7. Nassar, H., Qureshi, H., Adsay, N. V., Volkanadsay, N., & Visscher, D. (2006). Clinicopathologic analysis of solid papillary carcinoma of the breast and associated invasive carcinomas. The American Journal of Surgical Pathology, 30, 501–507.CrossRefGoogle Scholar
  8. Ni, Y. B., & Tse, G. M. (2016). Pathological criteria and practical issues in papillary lesions of the breast – A review. Histopathology, 68, 22–32.CrossRefGoogle Scholar
  9. Otsuki, Y., Yamada, M., Shimizu, S., Suwa, K., Yoshida, M., Tanioka, F., Ogawa, H., et al. (2007). Solid-papillary carcinoma of the breast: Clinicopathological study of 20 cases. Pathology International, 57, 421–429.CrossRefGoogle Scholar
  10. Piscuoglio, S., Ng, C. K. Y., Martelotto, L. G., Eberle, C. A., Cowell, C. F., Natrajan, R., Bidard, F. C., et al. (2014). Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast. Molecular Oncology, 8, 1588–1602.CrossRefGoogle Scholar
  11. Rabban, J. T., Koerner, F. C., & Lerwill, M. F. (2006). Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: A potentially difficult distinction resolved by cytokeratin 5/6. Human Pathology, 37, 787–793.CrossRefGoogle Scholar
  12. Tan, B. Y., Thike, A. A., Ellis, I. O., & Tan, P. H. (2016). Clinicopathologic characteristics of solid papillary carcinoma of the breast. American Journal of Surgical Pathology, 40, 1334–1342.CrossRefGoogle Scholar
  13. Turashvili, G., Brogi, E., Morrow, M., Hudis, C., Dickler, M., Norton, L., & Wen, H. Y. (2017). The 21-gene recurrence score in special histologic subtypes of breast cancer with favorable prognosis. Breast Cancer Research and Treatment, 165, 65–76.CrossRefGoogle Scholar
  14. Wei, S. (2016). Papillary lesions of the breast: An update. Archives of Pathology & Laboratory Medicine, 140, 628–643.CrossRefGoogle Scholar
  15. Yoshimura, N., Murakami, S., Kaneko, M., Sakatani, A., Hirabayashi, N., & Takiyama, W. (2013). Synchronous bilateral solid papillary carcinomas of the breast. Case Reports in Surgery, 2013, 812129.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Elena Vissio
    • 1
  • Caterina Marchiò
    • 1
    • 2
  • Anna Sapino
    • 1
    • 2
    Email author
  1. 1.Department of Medical SciencesUniversity of TorinoTorinoItaly
  2. 2.Candiolo Cancer Institute FPO-IRCCSUnit of PathologyCandioloItaly