Pathology Board Review: Breast Lesions
Quiz Question 1
Clinical Vignette
A 62-year-old postmenopausal woman presents with a new, ill-defined palpable area in her left breast, noted on self-exam. Mammography reveals an area of architectural distortion in the upper outer quadrant without distinct calcifications. Ultrasound confirms an ill-defined hypoechoic area. An MRI was performed, showing non-mass enhancement extending more broadly than initially appreciated. A core biopsy is performed, and an image from the biopsy is shown below.
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What is the most likely diagnosis?
A. Invasive lobular carcinoma (Correct Answer)
Explanation: Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer. Histologically, classic ILC is characterized by discohesive tumor cells that infiltrate the stroma, often in a single-file or "Indian file" pattern. These cells are typically small, with round to oval nuclei, inconspicuous nucleoli, and scant cytoplasm. Intracytoplasmic lumina may be present. A key feature is the loss of E-cadherin expression, which contributes to the discohesive nature of the cells. The clinical presentation of an ill-defined mass or architectural distortion, especially with more extensive disease on MRI than mammography/ultrasound, is common for ILC. The provided image demonstrates tumor cells infiltrating in a linear, single-file pattern with minimal stromal reaction, characteristic of ILC.
Image: Labeled example of Invasive Lobular Carcinoma showing single-file infiltration.
B. Invasive ductal carcinoma, NST
Explanation: Invasive ductal carcinoma of No Special Type (IBC-NST), also known as invasive carcinoma NST, is the most common type of invasive breast cancer. It is a diagnosis of exclusion, meaning it lacks the specific features of special type carcinomas. IBC-NST typically forms nests, cords, trabeculae, or sheets of tumor cells, often with glandular/tubular differentiation to varying degrees. Unlike ILC, IBC-NST cells are generally cohesive and express E-cadherin. The stroma is often desmoplastic. While it can present as an ill-defined mass, the single-file infiltrative pattern seen in the question image is not typical for IBC-NST. The image provided for this distractor shows a syncytial growth pattern, which is very different from the question image.
Image: Labeled example of Invasive Breast Carcinoma of No Special Type (with medullary pattern) showing cohesive sheets of cells.
C. Ductal Carcinoma In Situ (DCIS)
Explanation: Ductal Carcinoma In Situ (DCIS) is a non-invasive breast cancer where neoplastic epithelial cells are confined to the ductal-lobular system, meaning they have not breached the basement membrane. DCIS can have various architectural patterns (e.g., cribriform, solid, micropapillary, comedo). While DCIS is often a precursor to invasive carcinoma, the question image shows cells infiltrating the stroma, which by definition excludes DCIS.
Image: Labeled example of Ductal Carcinoma In Situ (low-grade cribriform pattern) showing neoplastic cells confined within duct structures.
D. Sclerosing adenosis
Explanation: Sclerosing adenosis is a benign proliferative breast lesion. It is characterized by an increased number of acini and stromal fibrosis, leading to compression and distortion of the glandular elements, but the overall lobular architecture is maintained. A myoepithelial layer is present. The infiltrative pattern of single, discohesive cells in the question image is not a feature of sclerosing adenosis.
Image: Labeled example of Sclerosing Adenosis.
E. Tubular carcinoma
Explanation: Tubular carcinoma is a well-differentiated type of invasive breast cancer characterized by well-formed, angulated tubules lined by a single layer of epithelial cells. Its hallmark is the formation of these distinct tubules, not the single-file infiltrative pattern of discohesive cells seen in the question image.
Image: Labeled example of Tubular Carcinoma.
Quiz Question 2
Clinical Vignette
A 48-year-old woman undergoes screening mammography which reveals a 0.8 cm area of focal asymmetry with grouped punctate and amorphous microcalcifications in her right breast. There is no discrete palpable mass. A stereotactic core needle biopsy is performed. An image from the biopsy is shown below.
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Based on the image and clinical presentation, what is the most likely diagnosis?
C. Sclerosing adenosis (Correct Answer)
Explanation: Sclerosing adenosis is a benign proliferative lesion of the breast, often seen as a component of fibrocystic changes. It is characterized by a proliferation of acini and stromal fibrosis, leading to compression and distortion of the glandular elements. However, it maintains a lobular architecture at low power. The glands are lined by both epithelial and myoepithelial cells, and the myoepithelial layer is intact and often prominent. Microcalcifications within the lumens are common. The question image shows distorted and compressed glands, some back-to-back, within a fibrotic stroma, consistent with sclerosing adenosis. The overall lobulocentric pattern, though not fully visible in a single high-power field, is a key feature. The clinical presentation with microcalcifications is also typical.
Image: Labeled example of Sclerosing Adenosis showing distorted, compressed glands, some appearing back-to-back, with stromal fibrosis and a maintained lobulocentric pattern.
A. Microglandular adenosis
Explanation: Microglandular adenosis (MGA) is a rare benign lesion characterized by a haphazard proliferation of small, uniform, round glands that infiltrate the stroma and adipose tissue. These glands are lined by a single layer of cuboidal cells and characteristically lack a myoepithelial layer. The lumens often contain dense, eosinophilic, colloid-like secretions. MGA is typically S100 positive and ER/PR negative. This differs from the image, which shows more compressed and distorted glands, and sclerosing adenosis retains its myoepithelial layer.
Image: Labeled example of Microglandular Adenosis showing small, round, open glands with eosinophilic secretions, infiltrating fat, and lacking a myoepithelial layer.
B. Tubular carcinoma
Explanation: Tubular carcinoma is a well-differentiated invasive carcinoma composed predominantly (≥90%) of single-layered, angulated or teardrop-shaped tubules infiltrating a desmoplastic stroma. These tubules lack a myoepithelial layer. Apical snouts are a characteristic feature of the epithelial cells. While sclerosing adenosis can sometimes be a mimic of tubular carcinoma due to distorted glands, tubular carcinoma consists of well-formed, open (though often angulated) tubules that are truly infiltrative and lack myoepithelial cells. Sclerosing adenosis, in contrast, retains myoepithelial cells and maintains a lobulocentric architecture.
Image: Labeled example of Tubular Carcinoma showing angulated tubules lined by a single layer of cells infiltrating a desmoplastic stroma.
D. Collagenous spherulosis
Explanation: Collagenous spherulosis is a benign incidental finding, often seen within other benign proliferative lesions like sclerosing adenosis or papillomas. It is characterized by intraductal or intra-acinar clusters of myoepithelial-like cells surrounding eosinophilic, acellular spherules of basement membrane material. This appearance is quite distinct from the diffuse glandular proliferation and stromal alteration seen in the question image and in sclerosing adenosis. The spherules are a key feature.
Image: Labeled example of Collagenous Spherulosis showing intraductal eosinophilic spherules surrounded by bland cells.
Quiz Question 3
Clinical Vignette
A 55-year-old woman presents for her annual screening mammogram. A 0.7 cm spiculated density with central radiolucency and architectural distortion is noted in the left breast. No definite calcifications are associated. Ultrasound shows an irregular hypoechoic mass with posterior shadowing. A core biopsy is performed.
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What is the most likely diagnosis given this appearance?
B. Radial scar / Complex sclerosing lesion (Correct Answer)
Explanation: Radial scars (if <1 cm) and complex sclerosing lesions (if ≥1 cm) are benign proliferative lesions characterized by a central fibroelastotic core with entrapped ducts, from which ducts and lobules radiate outwards. Radiologically, they often present as spiculated masses mimicking carcinoma, as described in the vignette. The question image shows a central sclerotic core with radiating tubular structures, consistent with this entity. Entrapped ducts within the core retain their myoepithelial layer.
Image: Labeled example of a Radial Scar showing a central fibroelastotic core and radiating ducts.
A. Tubular carcinoma
Explanation: Tubular carcinoma is an invasive carcinoma characterized by well-formed, angulated tubules lacking a myoepithelial layer and infiltrating a desmoplastic stroma. While it can appear spiculated on imaging, it lacks the characteristic central fibroelastotic core and radiating benign structures of a radial scar. The tubules in tubular carcinoma are malignant and infiltrative, whereas the entrapped glands in a radial scar are benign and retain myoepithelial cells.
Image: Labeled example of Tubular Carcinoma.
C. Invasive lobular carcinoma
Explanation: Invasive lobular carcinoma typically infiltrates as single-file strands or targets around ducts, with discohesive cells due to E-cadherin loss. It does not form the complex stellate architecture with a central scar seen in radial scars. While both can cause architectural distortion, their microscopic appearances are very different.
Image: Labeled example of Invasive Lobular Carcinoma.
D. Sclerosing adenosis
Explanation: Sclerosing adenosis is a benign lesion with proliferation of acini and stromal fibrosis, leading to compressed and distorted glands. It is lobulocentric and, while it can be part of a complex sclerosing lesion, it lacks the characteristic central fibroelastotic core and radiating pattern of a radial scar when considered as the primary diagnosis for the image shown.
Image: Labeled example of Sclerosing Adenosis.
Quiz Question 4
Clinical Vignette
A 68-year-old woman presents with a 2.5 cm palpable firm mass in her right breast. Mammography shows a spiculated mass with associated pleomorphic calcifications. Axillary lymph nodes appear enlarged on ultrasound. A core biopsy of the breast mass is performed.
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What is the most likely diagnosis?
C. Invasive micropapillary carcinoma (Correct Answer)
Explanation: Invasive micropapillary carcinoma (IMPC) is an aggressive variant of invasive breast cancer. Histologically, it is characterized by small, hollow, or morula-like clusters of neoplastic cells that appear to be floating within clear stromal spaces (pseudo-lymphovascular spaces). A key feature is the "inside-out" growth pattern, where the apical surface of the cells (often highlighted by EMA/MUC1 staining) faces the stroma (reversed polarity). These clusters lack true fibrovascular cores. IMPC is often associated with extensive lymphovascular invasion and a high frequency of lymph node metastasis, fitting the clinical concern for enlarged axillary nodes. The question image shows these characteristic cell clusters in clear spaces.
Image: Labeled example of Invasive Micropapillary Carcinoma showing morula-like clusters in clear spaces with reverse polarity.
A. Invasive ductal carcinoma, NST
Explanation: While IMPC is a type of invasive ductal carcinoma, "NST" (No Special Type) implies it lacks the specific features of IMPC. IBC-NST typically forms more cohesive nests, glands, or sheets and does not exhibit the characteristic micropapillary clusters with reversed polarity in clear stromal spaces.
Image: Labeled example of Invasive Breast Carcinoma of No Special Type.
B. Papillary DCIS
Explanation: Papillary DCIS is an in situ lesion, meaning the neoplastic cells are confined to ducts and have not invaded the stroma. It forms true papillae with fibrovascular cores lined by neoplastic cells, lacking a myoepithelial layer on the stalks. The question image shows stromal invasion and lacks true fibrovascular cores within the clusters, features inconsistent with Papillary DCIS.
Image: Labeled example of Papillary DCIS showing arborizing fibrovascular cores lined by monotonous cells.
D. Mucinous carcinoma
Explanation: Mucinous carcinoma is characterized by nests or clusters of tumor cells floating in abundant extracellular mucin pools. While some mucinous carcinomas can have a micropapillary component (micropapillary variant of mucinous carcinoma), the primary feature is the mucin. The question image shows clear stromal spaces around cell clusters, not prominent mucin pools. Pure IMPC lacks the abundant extracellular mucin of mucinous carcinoma.
Image: Labeled example of Mucinous Carcinoma showing tumor cells in pools of extracellular mucin.
Quiz Question 5
Clinical Vignette
A 72-year-old man presents with a painless, firm, mobile 2 cm nodule in his left breast, discovered on routine physical examination. Mammography and ultrasound confirm a well-circumscribed, solid mass. A core biopsy is performed.
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Given the clinical context and image, what is the most likely diagnosis?
B. Myofibroblastoma (Correct Answer)
Explanation: Myofibroblastoma is a benign mesenchymal tumor composed of myofibroblasts, typically occurring in older men (though also in women). It presents as a well-circumscribed mass. Histologically, it shows spindle cells arranged in clusters or short fascicles separated by hyalinized collagen bundles. Cells have oval to spindle nuclei and scant eosinophilic cytoplasm, with low mitotic activity and minimal atypia. Variable amounts of interspersed mature adipose tissue can be seen. Immunohistochemically, these tumors are typically positive for CD34 and Desmin, and often ER/PR. The image shows bland spindle cells in fascicles with intervening collagen, consistent with myofibroblastoma.
Image: Labeled example of Myofibroblastoma showing bland spindle cells, collagen bands, and positive IHC for ER, CD34, and Desmin.
A. Fibromatosis (Desmoid Tumor)
Explanation: Fibromatosis is a locally aggressive fibroblastic/myofibroblastic proliferation. It typically presents as an ill-defined, firm, infiltrative mass, not usually well-circumscribed like the lesion in the vignette. Histologically, it shows bland, slender spindle cells in sweeping fascicles that infiltrate adjacent tissues, often entrapping ducts and lobules. Nuclear beta-catenin positivity is characteristic. It is typically CD34 and Desmin negative.
Image: Labeled example of Fibromatosis showing infiltrative fascicles of bland spindle cells.
C. Spindle cell lipoma
Explanation: Spindle cell lipoma is a benign adipose tissue tumor containing a variable mixture of mature adipocytes, bland spindle cells, and ropey collagen, often in a myxoid stroma. While it shares the 13q deletion with myofibroblastoma and can be a close mimic, particularly the lipomatous variant of myofibroblastoma, classic myofibroblastoma has more prominent fascicles of spindle cells and hyalinized collagen, and less emphasis on the adipocytic component compared to typical spindle cell lipoma. Desmin positivity is more characteristic of myofibroblastoma.
Note: No specific image for Spindle Cell Lipoma was available in the provided JSON. This entity is characterized by bland spindle cells, mature fat, and wiry collagen.
D. Solitary fibrous tumor
Explanation: Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that can occur in various locations, rarely in the breast. Histologically, SFTs are characterized by a patternless arrangement of bland spindle cells in a collagenous stroma, often with prominent "staghorn" or branching hemangiopericytoma-like vessels. Immunohistochemically, SFTs are characteristically positive for CD34, STAT6, and Bcl-2, but typically negative for Desmin. Myofibroblastoma is usually Desmin positive.
Note: No specific image for Solitary Fibrous Tumor of the breast was available in the provided JSON. This entity is characterized by bland spindle cells, staghorn vessels, and STAT6 positivity.