Indolent Yet Intriguing: High-grade Solid Papillary Carcinoma of the Breast

Breast Solid Papillary Carcinoma (SPC) is an uncommon malignancy that primarily affects elderly women, with an incidence of 1-2%. It is morphologically characterised by well-defined nodules with low-grade nuclear features, which are associated with fibrovascular cores and neuroendocrine development. Although SPC can be invasive or in-situ, the prognosis is generally quite good. Its morphology can mimic several precancerous conditions, leading to frequent misdiagnosis. Distinguishing this tumour from its various morphological equivalents is more straightforward when an appropriate Immunohistochemistry (IHC) panel is utilised. A 45-year-old woman presented with a retroareolar mass in her right breast. Sono-mammography revealed a firm, incompressible mass with irregular borders, calcifications, cystic changes, and necrosis. A right-side simple mastectomy was performed, and the tumour was diagnosed as triple-negative high-grade SPC of the breast with focal invasion. The tumour’s origin was ruled out, and the diagnosis was confirmed by a prominent histopathologist. This report discusses a case of SPC, emphasising invasion patterns and evaluating previous knowledge.

Immunohistochemistry, Invasive carcinoma, Neuroendocrine differentiation, Triple-negative breast cancer

A 45-year-old lady presented with an ulcerative retroareolar lesion measuring 7×7 cm in her right breast. She subsequently experienced pain, blood discharge, and nipple retraction. Sono-mammography suggested a firm, incompressible mass with uneven echotexture and irregular borders, as well as calcifications, cystic changes, and necrosis, all consistent with a Breast Imaging Reporting and Data System (BIRADS) IV lesion. A right simple mastectomy was performed, and the specimen was sent for histopathologic assessment.

The gross specimen showed a local excision of breast tissue measuring 8×7×4 cm, with a skin flap measuring 6×3 cm [Table/Fig-1]. The cut section revealed a well-circumscribed grey-white to brownish lump with a granular solid cut surface. The adjacent breast tissue displayed patchy grey-white areas. The base margin was 1.5 cm away, while the rest of the resection margins were 1.5, 3, 5, and 3 cm away [Table/Fig-2]. Microscopically, the tumour was well-circumscribed, consisting of a central sclerotic area and solid nodules comprised of sheets of cells separated by fibrovascular septae [Table/Fig-3]. The cells had enlarged, pleomorphic, hyperchromatic, mitotically active nuclei with clumped chromatin and moderate eosinophilic cytoplasm. The adjacent breast tissue showed Lobular Carcinoma in-situ (LCIS) and focal invasion, with no lymphovascular emboli or perineural invasion [Table/Fig-4].

[Table/Fig-1]:

Gross specimen of right breast mastectomy. An 8×7×4 cm local excision of the breast can be observed in the material, along with a 6×3 cm skin flap.

[Table/Fig-2]:

The cut surface of the gross specimen. A well-circumscribed grey, whitish to brownish lump with a granular, firm-cut surface was visible in the part that had been sliced. Patchy regions of grey-white breast tissue were visible nearby. The remaining resection margins are spaced 1.5, 3, 5, and 3 centimeters from the base.

[Table/Fig-3]:

Low magnification microscopic picture of Solid Papillary Carcinoma (SPC) breast- A well-circumscribed tumour with solid nodules and a core sclerotic region is observed under a microscope. The cells exhibit larger, pleomorphic hyperchromatic nuclei with clumped chromatin and mild eosinophilic cytoplasm (4x).

[Table/Fig-4]:

Low Magnification (4x) of Solid Papillary Carcinoma (SPC) - A well-circumscribed tumour in breast tissue was seen under a microscope. It had solid nodules without lympho-vascular emboli or perineural invasion, and a central sclerotic region. Arrows are marked at areas of invasion. (Images from left to right)

The results of IHC showed that the Oestrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2/neu (HER2/neu) were negative. P63 was also negative at the perimeter of the nodule [Table/Fig-5]. The tumour was negative for Thyroid Transcription Factor-1 (TTF-1), PAX8, and CDX2 on the IHC study, thus ruling out thyroid, ovarian, and gastrointestinal origins. The diagnosis of pure type SPC with invasion was confirmed by negative results for all neuroendocrine markers, including CD56, chromogranin A, and synaptophysin. The tumour was diagnosed as triple-negative high-grade SPC of the breast with focal invasion (T3N0M0), with a Modified Bloom-Richardson score of the invasive components being 9 (3+3+3) and no lymphovascular emboli or perineural invasion [1]. The tumour’s origin was ruled out, and a second review by a senior histopathologist confirmed the diagnosis.

[Table/Fig-5]:

a) IHC Oestrogen Receptor (ER) showing negative for breast lesion (4x); b) IHC Progesterone Recepter (PR) showing negative for breast lesion (4x); c) IHC HER2/neu showing negative for breast lesion (4x); d) p63 negativity suggests that this lesion may be an invasive carcinoma, as myoepithelial cells typically express p63 (4x).

The SPC of the breast is a unique intraductal papillary tumour that often affects women in their 70s [2]. It has a prevalence of 1-2% and distinct clinicopathological characteristics [3]. Cancer in-situ (SPC) is a type of cancer that often behaves indolently until it becomes associated with invasion [4]. The 5^th edition of the 2019 World Health Organisation (WHO) classification divides papillary neoplasms into five categories: intraductal papilloma, papillary Ductal Carcinoma in-situ (DCIS), encapsulated papillary carcinoma, SPC (both in-situ and invasive), and invasive papillary carcinoma [5]. The WHO classification recognises SPC for staging purposes, even in cases with unclear or dubious invasive foci. A research by Guo S et al., showed that SPCs lack myoepithelial cells and can lead to local stromal/muscle infiltration, as well as lymph node or distant metastatic spread, which presents a diagnostic challenge for pathologists [6]. SPCs have an excellent prognosis, with few incidences of local recurrence, distant metastasis, and death [7]. According to a literature search on Medline, PubMed, and Scopus, which included 297 reported cases, 90% of cases involve localised lesions in pre- and postmenopausal females, with only 0.4% having upfront metastases [8]. This report discusses the case of a 45-year-old Indian female who have triple-negative SPC with focal invasion.

In 1956, Maluf HM and Koerner FC identified a specific breast lesion called “SPC,” primarily found in elderly women [9]. The WHO defines SPC as closely spaced expansile cellular nodules with delicate fibrovascular core and a solid development pattern. Pseudo-rosettes and nuclear palisading encircling stromal centers are visible in these confined nodules packed with neoplastic cells, which frequently exhibit low to intermediate nuclear grades. These nodules are considered non invasive. They may display low-grade cytological traits, Neuroendocrine Differentiation (NED), or a mucinous invasive component. SPCs appear as circumscribed nodules filled with neoplastic cells, often monomorphic with low to intermediate nuclear grades. Notably, they differ by forming circumscribed nodules that obscure the underlying papillary features and the solid cellular development of cancerous cells, supported by fibrovascular cores [5]. This may bear similarities to other disorders such as DCIS, lobular neoplasia, florid ductal hyperplasia, and intracystic papillary carcinoma [10].

SPC tumours are detected using mammography and ultrasonography, with 50% being occult [11]. Ultrasonography identifies BIRADS-IV or BIRADS-V lesions, while Magnetic Resonance Imaging (MRI) has high sensitivity due to its circumscribed margins, heterogeneous signal intensity, and high apparent diffusion coefficient values [12]. Microscopically, SPCs present as circumscribed nodules filled with neoplastic cells, often monomorphic with low to intermediate nuclear grades, appearing non invasive due to their circumscription, and occasionally displaying pseudo-rosettes and nuclear palisading [13]. SPC is characterised by intracellular mucinous differentiation and extracellular mucin synthesis, but it must be distinguished from invasive mucinous carcinoma. Capella type B mucinous carcinoma can resemble SPC, particularly when mucin synthesis decreases [10]. NED is a crucial IHC characteristic for detecting breast cancer, as it is observed in over half of all reported SPC cases [14]. CK5/6 immunopositivity and NED help differentiate SPC from other common breast neoplasms [15]. Breast biomarkers indicate that SPCs have a luminal phenotype, expressing PR and ER receptors but lacking HER2. They possess a basic genome with minor modifications.

Additional genetic traits include the deletion of chromosome 16q and the gain of chromosomes 1p and 16p. Furthermore, SPCs express the genes DOC7.23, ASCL1, and RET, which are implicated in neuroendocrine development [14]. Among the previously reported 297 cases, only 15 were triple-negative, and only three of these exhibited high-grade cytological characteristics [7]. Due to its triple-negative status, localised invasion, and lack of NED, this particular case is distinct. Invasive Lobular Carcinomas (ILCs) with a solid-papillary growth pattern, similar to solid and encapsulated papillary carcinoma, are characterised by the absence of NED, the presence of in-situ lobular carcinoma, and localised merging of solid-papillary areas with conventional lobular carcinoma. Both solid-papillary and classic lobular components exhibit similar CDH1 mutations and copy number changes. The diagnosis of ILC is validated by the presence of deleted myoepithelium, positive cytoplasmic P120, and negative E-cadherin in IHC [16].

Since, there is no relationship between the type of surgery and the likelihood of recurrence, local therapy is the best course of treatment for solid papillary breast cancer. However, treatment rates vary significantly, with mastectomy rates ranging from 7-88% [17]. Mastectomy and removal of axillary lymph nodes should be avoided in cases of small, well-defined solid papillary breast cancer. Pure solid papillary breast cancer responds best to adequate local excision, with or without hormone therapy [17]. Present study findings emphasise the need to adopt a broad IHC panel to consistently differentiate solid papillary carcinoma from other breast neoplasms. Given [Table/Fig-6], highlight the key features of differentials that can mimic a solid papillary neoplasm of the breast [10].

The SPC is a rare and distinct type of breast cancer characterised by well-defined nodules and low-grade nuclear features. Diagnosis is challenging due to its similarity to other breast conditions. A comprehensive immunohistochemical panel is needed to reliably differentiate SPC from other breast neoplasms. Diagnostic markers include the absence of myoepithelial cells and NED. SPCs have a favourable prognosis, with a low chance of local recurrence or distant metastasis. However, therapy should be adjusted based on the tumour’s invasiveness. Local excision is the best treatment for non invasive SPC, while more aggressive surgical interventions may be necessary for invasive cases. Further research and case reporting are needed to enhance knowledge and management of this specific type of breast cancer.

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