Other Malignant Tumors of the Breast

Slide 1 · Other malignant tumors of the breast

Breast lymphomas · implant-associated ALCL · skin malignancies · secondary tumors

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish primary mammary carcinoma from breast involvement by non-mammary malignancies.

Recognize the breast lymphoma spectrum, including implant-associated ALCL and Burkitt lymphoma.

Select morphology-guided immunohistochemistry and integrate clinical history.

Slide 3 · Four groups outside conventional breast carcinoma

Hematolymphoid

B-cell and T-cell lymphomas

Implant-associated

ALCL of the peri-implant capsule

Cutaneous

Malignancy arising in breast skin

Metastatic

Extramammary malignancy in breast

Slide 4 · The numerical context: Uncommon, not negligible

< 5%

Together, hematolymphoid tumors, cutaneous malignancies, and extramammary metastases constitute <5% of malignant breast tumors.

The predominant differential remains a primary mammary carcinoma.

Small prevalence makes deliberate clinical and histologic recognition important.

Slide 5 · The breast contains several diagnostic compartments

Epidermis and dermis

Cutaneous primary malignancy

Parenchyma

Primary carcinoma or lymphoma / metastasis

Peri-implant capsule

Implant-associated ALCL

Schematic: Compartments shown separately for site-of-origin reasoning

Slide 6 · “Tumor in the breast” does not establish its origin

Breast lesion

Determine lineage

Determine origin

Classify lesion

Anatomic location is distinct from tissue lineage and site of origin.

A core biopsy may sample a secondary process rather than a mammary primary.

Lineage, clinical history, and distribution must be reconciled before final classification.

Slide 7 · Three questions at the first sign-out review

1

Is the neoplasm epithelial, lymphoid, melanocytic, or another lineage?

2

Does the patient have systemic disease, an implant, or a prior extramammary malignancy?

3

Is the lesion centered in breast tissue, skin, or the implant capsule?

Slide 8 · Red flags on a limited core biopsy

Lymphoid pattern

Non-mammary pattern

Clinical discordance

Discohesive monotonous lymphoid cells rather than cohesive gland-forming epithelium.

Unexpected melanocytic or other non-mammary cytomorphology.

No demonstrable in situ mammary lesion, especially with a known extramammary cancer.

Slide 9 · First-line lineage triage is a differential, not a panel for every case

Review H&E

Check history

Target lineage panel

Interpret together

Morphology and history determine targeted immunostains.

Broad epithelial markers help establish epithelial differentiation; CD45 and lineage-specific lymphoid markers assess hematolymphoid disease.

Melanocytic markers can help when morphology/history raises melanoma.

Slide 10 · A negative mammary marker alone is not proof of metastasis

Mammary carcinomas vary in expression of differentiation markers.

No single immunostain perfectly identifies primary breast carcinoma.

Convergent morphology, in situ component, panel results, and clinical history carry more weight.

Slide 11 · Breast lymphoma: Primary or secondary involvement

Primary breast lymphoma

Secondary breast involvement

Primary breast lymphoma arises/presents predominantly in breast tissue without established disseminated lymphoma.

Secondary breast lymphoma represents involvement by lymphoma occurring elsewhere.

The distinction is clinical as well as histopathologic.

Slide 12 · Why “primary” requires staging context

Breast histology confirms lymphoma lineage; It cannot alone demonstrate that the breast is the primary site.

Clinical examination, imaging, nodal status, and prior lymphoma history are needed.

Ipsilateral axillary disease may coexist with primary breast lymphoma in classic clinical definitions.

Slide 13 · Most primary breast lymphomas are B-cell neoplasms

B-cell

B-cell tumors as the dominant group among primary breast lymphomas.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype.

The mammary site does not override the lymphoma subtype diagnosis.

Slide 14 · DLBCL: The morphologic clue is a destructive large-cell infiltrate

Typical DLBCL shows sheets of large atypical lymphoid cells.

Nuclei commonly have open chromatin and conspicuous nucleoli.

Loss of normal mammary architecture follows diffuse neoplastic infiltration.

Original cellular schematic — not histologic evidence

Slide 15 · DLBCL expresses a mature B-cell program

CD19 and CD20 expression support a mature B-cell lineage.

CD10 and BCL6 may be expressed; Phenotype varies across cases.

Histology and immunophenotype must exclude other defined large B-cell entities.

Slide 16 · DLBCL is biologically heterogeneous

B-cell genetic events

Altered growth / survival

Large B-cell proliferation

BCL6 deregulation can interfere with normal germinal-center differentiation and growth control.

BCL2 dysregulation supports cell survival in some tumors.

MYC alteration is not unique to DLBCL and requires context-sensitive classification.

Slide 17 · The lymphoma–carcinoma morphological divide

Lymphoma

Breast carcinoma

Lymphoma often consists of discohesive hematolymphoid cells infiltrating native stroma.

Invasive breast carcinoma typically demonstrates epithelial differentiation, albeit sometimes subtle.

Morphology determines whether CD45/B-cell markers or broad cytokeratin assessment is prioritized.

Slide 18 · A focused DLBCL work-up has more than one purpose

Lineage: CD45 with CD20/PAX5 and other appropriate B-cell markers.

Classification: Selected germinal-center, activation, EBV, and genetic investigations as clinically indicated.

Exclusions: Other aggressive B-cell lymphoma entities and non-lymphoid mimics.

Slide 19 · Primary breast lymphoma is not managed as ordinary carcinoma

Lymphoid lineage

Subtype and staging

Hematology pathway

A diagnosis of lymphoma changes systemic staging and the therapeutic pathway.

Histologic subtype and disease extent determine hematology-directed treatment.

An incorrect carcinoma label may lead to inappropriate surgical management.

Slide 20 · Case: A rapidly growing breast mass

Clinical-pathology problem

A core biopsy shows diffuse sheets of large atypical cells, no glands, and strong CD20 positivity.

There is no established prior lymphoma; Staging is not yet complete.

Question: What can be diagnosed now, and what remains unresolved?

Slide 21 · Case resolution: Subtype first; Site designation second

Diagnostic interpretation

The biopsy supports a large B-cell lymphoma, with DLBCL classification after the appropriate exclusions.

“Primary breast lymphoma” requires clinical exclusion of a disseminated lymphoma.

Do not infer primary origin solely from biopsy location.

Slide 22 · Implant-associated ALCL is a distinct clinical setting

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma.

The disorder to breast implants and notes chronic inflammation as a possible contributing mechanism.

Mechanistic uncertainty should not be translated into a proven single causal pathway.

Slide 23 · The relevant compartment is the implant capsule

Implant

Device within capsule

Effusion space

Potential diagnostic cells

Fibrous capsule

Assess invasion and extent

Schematic: Compartments shown separately for site-of-origin reasoning

Slide 24 · Delayed peri-implant change is the clinical trigger

Implant history

Late swelling / mass

Fluid or tissue sampling

Pathology review

Late breast swelling, fluid collection, or a new peri-implant mass warrants evaluation.

An implant-related malignancy must not be presumed from symptoms alone.

The FDA recommends explicit assessment of BIA-ALCL in symptomatic late peri-implant presentations.

Slide 25 · Clinical risk is associated especially with textured devices

BIA-ALCL is associated particularly with textured-surface implant exposure.

Implant exposure history should document product type and any preceding implants where possible.

Risk association does not substitute for cytologic/histologic proof in an individual patient.

Slide 26 · Late peri-implant effusion: Material allocation matters

Aspirated fluid

Cytospins / smears

Cell block ± flow

Integrated report

Fresh seroma fluid is needed for cytomorphology and creation of a cell block.

The cell block supports immunohistochemistry; Ancillary flow cytometry may be useful.

Pathology requisitions should explicitly mention possible implant-associated lymphoma.

Slide 27 · BIA-ALCL cytology: Large atypical cells

Aspirates may contain large pleomorphic cells with prominent nucleoli and irregular nuclei.

Some cells show kidney- or horseshoe-shaped “hallmark” nuclei.

The inflammatory background can coexist with malignant cells and should not falsely reassure.

Original cellular schematic — not histologic evidence

Slide 28 · The defining immunophenotypic pattern

CD30

ALK

T-cell markers

Strong CD30 expression in the neoplastic cells is characteristic.

ALK protein is typically negative in BIA-ALCL.

T-cell marker expression can be variable or incomplete.

Slide 29 · CD30 positivity is necessary context—not sufficient by itself

Reactive activated lymphocytes may also stain for CD30.

Diagnosis requires cytologic atypia, lesion context, and an appropriate immunophenotypic profile.

Isolated CD30-positive cells do not independently establish BIA-ALCL.

Slide 30 · Avoid a false-negative work-up of low-cellularity fluid

A specimen with few diagnostic cells can be nondiagnostic despite suspicious clinical findings.

A clear request for cell block and targeted stains improves specimen use.

Persistent suspicion warrants specialist review and consideration of repeat or additional tissue sampling.

Slide 31 · Peri-implant mass: Sample the solid component

A discrete mass requires tissue sampling to define infiltrative disease.

The morphology and immunophenotype still need to establish lymphoma, not carcinoma or another mass lesion.

Capsule involvement must be evaluated separately from luminal effusion cytology.

Slide 32 · Capsulectomy examination is an anatomic assessment

Orient specimen

Inspect / map capsule

Sample involved areas

Assess extent / margin

Document the implant–capsule relationship and any focal thickening or mass.

Sample the capsule sufficiently to detect luminal, intracapsular, and extracapsular lymphoma.

Margins and extent are meaningful only when the specimen and orientation are adequate.

Slide 33 · Progression can extend from lumen to surrounding tissue

Peri-implant fluid

Cells in luminal compartment

Capsule surface

Cells lining inner capsule

Capsular invasion

Cells entering fibrous tissue

Beyond capsule

Extension to adjacent tissue

Schematic: Progression in relation to fibrous capsule; Not a histologic image

Slide 34 · Reactive peri-implant inflammation is a key mimic

Reactive response

BIA-ALCL

Inflammation, foreign-body reaction, and some reactive cells can coexist in a capsule.

Search for an atypical cohesive or dispersed population of large cells with concordant immunophenotype.

CD30 staining must be interpreted with cell identity and architectural distribution.

Slide 35 · A negative ALK result is supportive, not a stand-alone diagnosis

ALK negativity helps distinguish BIA-ALCL from ALK-positive systemic ALCL.

ALK-negative T-cell lymphomas and other lesions remain in the broader differential.

The peri-implant clinical and anatomic presentation is critical.

Slide 36 · Prognostic evaluation depends on disease extent

Disease confined to fluid/capsule differs clinically from a mass with infiltration outside the capsule.

Pathology should report detectable extension and margin status when assessable.

Multidisciplinary management uses extent, not CD30 staining intensity, to guide decisions.

Slide 37 · Case: Delayed swelling around an implant

Clinical-pathology problem

Several years after placement, a patient develops recurrent unilateral swelling and a peri-implant effusion.

Fluid cytology shows large pleomorphic cells; Cell block is strongly CD30 positive and ALK negative.

Question: What additional context and specimen evaluation are necessary?

Slide 38 · Case resolution: Confirm lineage and map the lesion

Diagnostic interpretation

Interpret morphology and full panel to establish BIA-ALCL rather than relying on CD30 alone.

Assess imaging for a mass; Examine excised capsule for infiltration and extent when available.

Communicate the diagnosis for coordinated specialist management.

Slide 39 · Breast Burkitt lymphoma: An uncommon but distinctive presentation

Massive bilateral breast involvement in young patients, sometimes during pregnancy or lactation.

This pattern should prompt consideration of a high-grade lymphoma alongside epithelial and inflammatory causes.

The clinical setting is a clue, not a criterion sufficient for diagnosis.

Slide 40 · Burkitt lymphoma is a rapidly proliferating mature B-cell neoplasm

MYC rearrangement

Proliferation

Apoptotic turnover

Macrophage clearance

MYC deregulation drives a marked increase in cellular growth and metabolic activity.

Very high proliferation and apoptosis can occur together.

High cellular turnover helps explain the frequent conspicuous “starry-sky” pattern.

Slide 41 · MYC rearrangement: Essential molecular context

Burkitt lymphoma is associated with MYC rearrangement, usually involving an immunoglobulin locus.

The classic translocation is IGH::MYC, t(8;14).

MYC alteration alone is not synonymous with Burkitt lymphoma; Morphology and phenotype remain necessary.

Slide 42 · “Starry sky” is a morphologic pattern, not a diagnosis

Interspersed macrophages ingest apoptotic fragments among dense tumor cells.

Their relatively pale cytoplasm produces the lighter “stars.”

The pattern is compatible with Burkitt but can occur in other rapidly proliferating disorders.

Original cellular schematic — not histologic evidence

Slide 43 · Burkitt lymphoma immunophenotype

The cells express mature B-cell markers including CD19 and CD20.

CD10 and BCL6 support germinal-center differentiation.

BCL2 is typically absent; Ki-67 activity is characteristically very high.

Slide 44 · Distinguish Burkitt from other high-grade B-cell lymphomas

Burkitt lymphoma

DLBCL / other HGBCL

Morphology, broad phenotype, and MYC partner alterations must be integrated.

DLBCL can also proliferate rapidly and can show MYC-related changes.

Current WHO-HAEM5 classification requires attention to other genetically defined high-grade B-cell entities.

Slide 45 · Why bilateral involvement changes the clinical question

Two rapidly growing masses in a pregnant/lactating patient raise concern for a systemic hematolymphoid process.

Bilateral distribution is suggestive but not specific.

Comprehensive staging and prompt hematology involvement are needed once lymphoma is confirmed.

Slide 46 · Case: Bilateral enlargement during lactation

Clinical-pathology problem

A young lactating patient has rapidly progressive bilateral breast masses.

Biopsy shows a monomorphic, highly proliferative B-cell infiltrate with abundant apoptotic debris.

Question: What diagnosis and confirmatory investigations belong at the top of the differential?

Slide 47 · Case resolution: Consider Burkitt and confirm the classification

Diagnostic interpretation

Evaluate CD20, germinal-center phenotype, BCL2, Ki-67, and MYC status in the morphologic context.

Differentiate Burkitt lymphoma from DLBCL and genetically defined high-grade B-cell lymphoma.

Do not label the presentation “mastitis” solely because the patient is lactating.

Slide 48 · Breast skin is a separate primary cancer compartment

Surface lesion

Epidermal origin

Dermal nodule

Dermal / metastatic differential

Deep mass

Breast parenchymal origin

Schematic: Compartments shown separately for site-of-origin reasoning

Slide 49 · Cutaneous squamous malignancy requires an epidermal correlation

A malignant squamous tumor centered in breast skin should be evaluated as a skin-based lesion.

Keratinization and intercellular bridges support squamous differentiation when present.

Determine whether the tumor connects to epidermis and whether another site could be primary.

Slide 50 · Melanocytic malignancy in breast skin vs breast tissue

A melanoma centered in the overlying skin differs from melanoma metastatic into breast parenchyma.

Epidermal junctional/in situ involvement supports a cutaneous primary when documented.

Clinical skin examination and tissue orientation are important for site assignment.

Slide 51 · A dermal tumor can be primary cutaneous or secondary

A nodule in the dermis is not automatically a primary skin malignancy.

A metastasis from another primary cancer can involve dermis or subjacent breast tissue.

Interpret the biopsy with anatomic depth and systemic cancer history.

Slide 52 · Skin lesion sampling must preserve anatomic relationships

Surface examination

Oriented biopsy

Identify layer

Assign likely origin

Superficial fragments may not show the full epidermis–dermis–breast interface.

Histologic connection to epidermis is informative when a primary epidermal tumor is suspected.

Describe where the malignant population is actually located; Avoid guessing origin from a small fragment.

Slide 53 · Metastatic disease to breast parenchyma is rare

Robbins specifically lists melanoma and ovarian carcinoma among common sources of breast metastases.

A breast lesion may be secondary to an established or previously unsuspected extramammary tumor.

The major practical issue is differentiation from primary mammary carcinoma.

Slide 54 · Clinical history has high diagnostic value

Review known malignancies, original pathology reports, interval, and treatment history.

A new breast lesion can still be metastatic even when imaging resembles a localized primary tumor.

Comparison with prior tumor slides, when available, can be decisive.

Slide 55 · Morphology can suggest metastasis before immunostaining

Features unusual for primary mammary carcinoma should prompt a search for another origin.

Absence of carcinoma in situ may support—but never prove—a metastatic explanation.

Certain cell types, pigment, or specialized growth patterns suggest specific extra-mammary primaries.

Slide 56 · A breast metastasis usually lacks a mammary in situ precursor

Supports mammary primary

Raises metastatic differential

DCIS/LCIS may establish a link to a breast primary in the correct setting.

Finding no in situ component is not diagnostic of metastasis because many core biopsies omit it.

Use negative evidence cautiously and avoid overconfident interpretation.

Slide 57 · Melanoma metastasis can mimic poorly differentiated carcinoma

Epithelioid melanoma may resemble a high-grade epithelial lesion.

Pigment may be absent; Cytology alone does not resolve lineage in every case.

Melanocytic markers need interpretation alongside cytokeratins and clinical history.

Slide 58 · SOX10 is an important diagnostic pitfall

SOX10-positive melanoma

SOX10-positive breast carcinoma

SOX10 can be expressed by melanoma and by some triple-negative mammary carcinomas.

SOX10 positivity alone does not distinguish these two processes.

A pan-cytokeratin and a broader melanocytic panel help resolve the differential.

Slide 59 · Ovarian carcinoma can metastasize to the breast

High-grade serous carcinoma from the tubo-ovarian tract may involve breast tissue.

WT1 and PAX8 can support Müllerian origin in the appropriate morphological context.

No single marker replaces comparison with the documented ovarian primary.

Slide 60 · Lineage panels are hypothesis-driven

Suspected origin

Directed positive lineage evidence

Essential competing differential

Lymphoma

CD45; B/T-cell markers

Poorly differentiated carcinoma

Melanoma

Melan-A, S100, HMB45

SOX10-positive carcinoma

Ovarian serous carcinoma

PAX8, WT1

Primary mammary carcinoma

Slide 61 · A practical algorithm for the unfamiliar breast malignancy

History and anatomy

Morphology

Targeted IHC

Origin / classification

Confirm anatomic compartment and review clinical cancer/implant history.

Use morphology to classify epithelial, lymphoid, melanocytic, or uncertain lineage.

Select focused IHC; Compare with prior tissue; Reconcile findings before issuing the final diagnosis.

Slide 62 · Case: A pigmented or amelanotic tumor in breast tissue

Clinical-pathology problem

A patient with previous cutaneous melanoma presents with a new breast nodule.

Biopsy is an atypical epithelioid proliferation without an identifiable in situ ductal component.

Question: Which differential and stain interpretation problems matter?

Slide 63 · Case resolution: Melanoma versus mammary carcinoma

Diagnostic interpretation

Compare biopsy with the prior melanoma and assess appropriate melanocytic markers.

Include epithelial markers because SOX10 can label some breast carcinomas.

Classify as metastatic melanoma only when the combined evidence supports that origin.

Slide 64 · Case: Breast mass in a patient with ovarian carcinoma

Clinical-pathology problem

An ovarian carcinoma survivor develops a new breast nodule.

Histology suggests high-grade carcinoma but no mammary in situ lesion is sampled.

Question: How should a proposed ovarian metastasis be established?

Slide 65 · Case resolution: Use a comparative origin panel

Diagnostic interpretation

Compare tumor morphology with the known tubo-ovarian primary.

Use PAX8/WT1 and mammary markers as a panel, interpreted in context.

Do not classify from absent DCIS or one positive marker alone.

Slide 66 · The most consequential diagnostic errors are classification errors

1

Calling lymphoma a carcinoma misdirects staging and treatment.

2

Calling metastatic melanoma a mammary primary misstates the site and disease burden.

3

Calling a late peri-implant seroma “benign inflammation” without appropriate evaluation can miss BIA-ALCL.

Slide 67 · Integrated pathology report: What must be made explicit

Tumor lineage, specific subtype, and what evidence supports it.

Anatomic compartment and the limits of site-of-origin attribution on the submitted specimen.

Relevant differential, ancillary results, and any need for clinical staging or comparative pathology.

Slide 68 · Synthesis: Use origin, lineage and clinical setting

Lymphoid mass

DLBCL, other primary or secondary lymphoma

Late implant effusion

Exclude BIA-ALCL

Skin-based lesion

Classify by cutaneous lineage

Unexpected carcinoma

Consider extramammary metastasis

Slide 69 · Five defensible take-home decisions

Rare breast malignancies need deliberate lineage triage, not blanket stain panels.

DLBCL dominates primary breast B-cell lymphoma; Primary versus secondary remains a clinical distinction.

BIA-ALCL requires peri-implant context, cytomorphology, CD30/ALK work-up, and extent assessment.

Burkitt can affect both breasts in pregnancy/lactation and demands molecularly informed classification.

Metastatic melanoma or ovarian carcinoma must be distinguished from a mammary primary.

Slide 70 · References and evidence boundaries

1. Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th ed. 2026. Ch. 23, p. 969; ch. 13 (lymphomas).

2. WHO-HAEM5 B-cell neoplasm review. J Clin Pathol. 2025. doi:10.1136/jcp-2025-210260.

3. FDA. Questions and Answers About Breast Implant-Associated ALCL (online clinical guidance).

4. Jaffe ES et al. Best Practices Guideline for BIA-ALCL Pathology. J Clin Oncol. 2020. doi:10.1200/JCO.19.02778.

5. Lee AHS. Histological diagnosis of breast metastases. J Clin Pathol. 2007. doi:10.1136/jcp.2006.046078.

6. Cimino-Mathews A. IHC in breast pathology. Mod Pathol. 2021. doi:10.1038/s41379-020-00697-3.