Miscellaneous Tumors

Slide 1 · Miscellaneous Tumors

of the Lung

Pulmonary hamartoma • Lymphangioleiomyomatosis • Inflammatory myofibroblastic tumor

Mediastinal masses and patterns of pulmonary metastasis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Classify less-common primary pulmonary lesions and recognize pulmonary metastases.

Relate hamartoma, lymphangioleiomyomatosis, and inflammatory myofibroblastic tumor morphology to pathogenesis.

Distinguish principal patterns of mediastinal masses and secondary pulmonary spread.

Apply morphology, clinical context, and molecular findings without overinterpreting a single clue.

Slide 3 · A heterogeneous group—not one tumor family

Primary lung lesions

Mediastinal masses

Metastatic tumors

The heading gathers tumors with different tissues of origin and behavior.

Hamartoma, lymphangioleiomyomatosis, and inflammatory myofibroblastic tumor receive focused coverage.

The associated unit also includes hematolymphoid lesions and metastatic spread.

Slide 4 · The first distinction is anatomic origin

Lung primary

Extra-pulmonary mass

Metastatic deposit

An intrapulmonary lesion is not necessarily a primary epithelial lung cancer.

Mediastinal lesions may compress or invade lung without originating within parenchyma.

A deposit from another organ can appear as a solitary pulmonary nodule.

Slide 5 · Mesenchymal tumors occur in the lung

The lung can harbor rare benign and malignant mesenchymal tumors.

Named examples include fibrous, smooth-muscle, adipocytic, vascular, and cartilaginous neoplasms.

This diverse group should not be conflated with common primary pulmonary carcinomas.

Fibrous or smooth muscle

Fat or cartilage

Vascular tissue

Schematic — not a histologic specimen

Slide 6 · Examples of benign pulmonary mesenchymal tumors

Type

Examples / tissue association

Fibrous

Fibroma

Smooth muscle

Leiomyoma

Adipocytic

Lipoma

Vascular

Hemangioma

Cartilaginous

Chondroma

These are examples listed, not a comprehensive classification.

Slide 7 · Examples of malignant pulmonary mesenchymal tumors

Tumor

Named lineage

Fibrosarcoma

Fibrous differentiation

Leiomyosarcoma

Smooth-muscle differentiation

Uncommon entities are named in the source; No grading system is supplied in this section.

Slide 8 · Hematolymphoid tumors may involve the lung

Pulmonary hematolymphoid tumors resemble counterpart lesions in other organs.

Lung involvement may be isolated, but often occurs with generalized disease.

Thus, the pulmonary mass or infiltrate may represent part of a systemic process.

Pulmonary isolated

Lung in systemic disease

Classify tissue lineage

Schematic — not a histologic specimen

Slide 9 · Named hematolymphoid and histiocytic lesions

Group

Robbins examples

Histiocytic

Langerhans cell histiocytosis

Lymphoid

Hodgkin lymphoma

EBV-associated lymphoid

Lymphomatoid granulomatosis: EBV-positive B-cell lymphoma

B-cell lymphoma

Low-grade extranodal marginal zone B-cell lymphoma

Robbins refers to Chapter 13 for further characterization.

Slide 10 · Isolated versus generalized lung involvement

An isolated pulmonary presentation and pulmonary involvement in generalized disease are both possible.

Recognizing a lymphoid lineage does not establish the anatomical extent of disease.

The textbook section does not provide detailed immunophenotypic algorithms for these lesions.

Primary lung

Mediastinal origin

Metastatic lesion

Schematic — not a histologic specimen

Slide 11 · Putting rare pulmonary lesions into context

A rounded nodule may be a hamartoma or inflammatory myofibroblastic tumor.

Diffuse cystic remodeling suggests a different mechanism, exemplified by lymphangioleiomyomatosis.

Multiple peripheral nodules often reflect secondary spread rather than a rare primary sarcoma.

Solitary nodule / mass

Diffuse cystic process

Secondary lung deposits

Schematic — not a histologic specimen

Slide 12 · Pulmonary hamartoma: Benign clonal lesion

Pulmonary hamartoma is a relatively common benign pulmonary lesion.

Despite its traditional name, the lesion is a clonal neoplasm.

Neoplastic mesenchyme and entrapped respiratory epithelium form its characteristic architecture.

Cartilage

Fat

Epithelial-lined cleft

Schematic — not a histologic specimen

Slide 13 · Why hamartoma is frequently incidental

It is often detected on routine chest radiography rather than because of tumor-related symptoms.

The usual radiographic appearance is a rounded opacity: A “coin lesion.”

A coin lesion is a radiographic pattern, not a definitive histologic diagnosis.

Rounded pulmonary nodule

Schematic — not a histologic specimen

Slide 14 · Hamartoma: Gross configuration

Most lesions are solitary and well circumscribed.

Most measure less than 3–4 cm in diameter.

The rounded outline correlates with the classic incidental imaging appearance.

Rounded pulmonary nodule

Schematic — not a histologic specimen

Slide 15 · Hamartoma: Defining microscopic architecture

Nodules of connective tissue intersect with epithelial clefts.

The connective-tissue and epithelial compartments have different biological origins.

Cleft lining represents entrapped respiratory epithelium.

Cartilage

Fat

Epithelial-lined cleft

Schematic — not a histologic specimen

Slide 16 · Connective-tissue elements in hamartoma

Cartilage is the most common connective-tissue constituent.

Fibrous tissue and fat may also be present.

The coexistence of different mature mesenchymal tissues is a characteristic clue.

Cartilage

Fat

Epithelial-lined cleft

Schematic — not a histologic specimen

Slide 17 · Epithelial clefts in hamartoma

The clefts are lined by ciliated or nonciliated respiratory epithelium.

The epithelium is interpreted as entrapped native tissue rather than the clonal tumor component.

The clefts are therefore central to architectural recognition and the chondroma differential.

Cartilage

Fat

Epithelial-lined cleft

Schematic — not a histologic specimen

Slide 18 · The paradox of the name “hamartoma”

Historical label

Clonal mesenchyme

Entrapped epithelium

The conventional name is retained in clinical-pathology usage.

Chromosomal abnormalities support neoplastic rather than purely malformative origin.

The epithelial element does not share the mesenchymal clonal interpretation in the source.

Slide 19 · Chromosomal alterations in hamartoma

Aberrations involving 6p21 or 12q14–q15 are described.

The alterations are found in the mesenchymal component.

These findings explain why the lesion is considered a genuine clonal neoplasm.

Genetic / molecular clue

Changes growth signaling

Explains biological subset

Schematic — not a histologic specimen

Slide 20 · Hamartoma is a two-compartment lesion

Compartment

Composition

Interpretation

Mesenchymal

Cartilage ± fibrous tissue ± fat

Clonal neoplastic component

Epithelial

Ciliated/nonciliated lined clefts

Entrapped respiratory epithelium

Do not infer clonality of the epithelial lining from the mesenchymal rearrangement.

Slide 21 · Pulmonary hamartoma versus chondroma

Feature

Hamartoma

Chondroma

Cartilage

Often prominent

Cartilaginous tumor

Entrapped epithelium

Present as lined clefts

Absent as defining feature

Diagnostic logic

Mixed tissue + clefts

Cartilage without entrapped epithelium

This comparison addresses the specific distinction stated.

Slide 22 · Case: A solitary incidental “coin lesion”

Clinical-pathology vignette

A rounded, well-circumscribed pulmonary opacity is discovered on a routine chest radiograph. A resected nodule contains cartilage, fat, and epithelial-lined clefts.

Pulmonary hamartoma

Reasoning

The mixed mesenchymal tissue and entrapped respiratory epithelium are more specific than imaging alone.

Slide 23 · Hamartoma: Four diagnostic anchors

Incidental, solitary, well-circumscribed pulmonary nodule.

Cartilage-dominant connective tissue with possible fat and fibrosis.

Respiratory-epithelium-lined clefts distinguish it from chondroma.

Chromosomal changes in mesenchyme establish its clonal neoplastic nature.

Cartilage

Fat

Epithelial-lined cleft

Schematic — not a histologic specimen

Slide 24 · Lymphangioleiomyomatosis: Clinical profile

LAM is a pulmonary disorder affecting primarily young women of childbearing age.

It is characterized by proliferation of perivascular epithelioid cells.

The key consequence is progressive structural distortion of lung tissue.

Cystic terminal airspaces

Schematic — not a histologic specimen

Slide 25 · LAM cells have dual differentiation

Lesional cells express markers of melanocytes and smooth muscle cells.

This dual identity characterizes the perivascular epithelioid cell phenotype.

The textbook does not require an individual named immunostain in this short section.

Perivascular epithelioid cell

Melanocytic

Markers

Smooth-muscle

Markers

Schematic — not a histologic specimen

Slide 26 · LAM: Proliferation to lung damage

Perivascular epithelioid cells

Tissue distortion

Airspace and lymphatic effects

The cell population expands within affected lung tissue.

Structural remodeling involves airspaces, interstitium, and lymphatic vessels.

Clinical symptoms arise from the resulting architectural damage.

Slide 27 · Cystic airspace change is central in LAM

Terminal airspaces undergo cystic, emphysema-like dilation.

Abnormal dilation disrupts the normal alveolar architecture.

This change underlies the textbook association with spontaneous pneumothorax.

Cystic terminal airspaces

Schematic — not a histologic specimen

Slide 28 · LAM: Interstitial thickening

Proliferating lesional cells contribute to interstitial thickening.

Thickening accompanies rather than replaces the cystic airspace changes.

Both findings are part of the same tissue-remodeling process.

Interstitial tissue changes

Schematic — not a histologic specimen

Slide 29 · LAM: Lymphatic obstruction

Expansion of the lesional population can obstruct lymphatic vessels.

Lymphatic obstruction is one of the three explicit structural consequences described.

It is important to distinguish this mechanism from cystic airspace dilation.

Lymphatic channel: Obstructed

Schematic — not a histologic specimen

Slide 30 · The three structural effects of LAM

Affected structure

Reported change

Pathology concept

Terminal airspaces

Cystic, emphysema-like dilation

Altered airspace architecture

Interstitium

Thickening

Remodeling between airspaces

Lymphatic vessels

Obstruction

Impaired lymphatic channels

Anatomic effects derive from the same proliferating cell population.

Slide 31 · TSC2 loss of function in LAM

Lesional cells frequently harbor loss-of-function mutations of TSC2.

TSC2 is a tumor suppressor locus also linked to tuberous sclerosis.

This molecular clue supports dysregulated growth signaling in LAM.

Genetic / molecular clue

Changes growth signaling

Explains biological subset

Schematic — not a histologic specimen

Slide 32 · Tuberin normally restrains mTOR

TSC2 gene

Tuberin protein

Negative regulation of mTOR

TSC2 encodes tuberin.

Tuberin is a negative regulator of mechanistic target of rapamycin (mTOR).

MTOR is a central regulator of cellular metabolism.

Slide 33 · TSC2 loss provides a growth-signaling rationale

Loss of TSC2 function

Reduced inhibitory restraint

Increased mTOR activity

The source links TSC2 loss of function to increased mTOR signaling.

Increased mTOR activity is implicated in pathogenesis.

The full mechanism of the disorder is not completely understood.

Slide 34 · LAM and tuberous sclerosis

The TSC2 locus is linked to tuberous sclerosis.

The genetic relationship helps contextualize LAM beyond the respiratory tract.

The text does not imply that every person with LAM has tuberous sclerosis.

Pulmonary isolated

Lung in systemic disease

Classify tissue lineage

Schematic — not a histologic specimen

Slide 35 · Estrogen: A plausible contributor, not a complete model

LAM has a strong predilection for young women.

Lesional cells often express estrogen receptors.

These observations suggest estrogen contributes to proliferation; The full pathogenesis remains incompletely understood.

Female predominance

Estrogen receptor expression

Suggested estrogen contribution

Schematic — not a histologic specimen

Slide 36 · LAM: Structural cause of pneumothorax

Cystic airspace changes

Fragile remodeled lung

Spontaneous pneumothorax

The source specifically relates spontaneous pneumothorax to emphysema-like changes.

Dyspnea is another common presenting symptom.

The presentation follows logically from architectural injury.

Slide 37 · LAM: Chronic clinical course

The disorder tends to progress slowly over several decades.

Prolonged progression does not mean the changes are clinically insignificant.

The source emphasizes ongoing deterioration of lung function as the therapeutic target.

Slow progression

Several decades

Ongoing function decline

Schematic — not a histologic specimen

Slide 38 · LAM: Treatment and disease control

Strategy

Textbook-supported effect

mTOR inhibition

Slows or prevents lung-function deterioration

Continuity of medication

Treatment must be continued indefinitely for sustained control

Lung transplantation

Identified in the textbook as the only curative option

These are source-specific statements, not a complete contemporary treatment guideline.

Slide 39 · Case: Progressive dyspnea and pneumothorax

Clinical-pathology vignette

A young woman has progressive dyspnea and a spontaneous pneumothorax. The lung shows cystic terminal-airspace dilation and perivascular epithelioid cell proliferation.

Lymphangioleiomyomatosis

Reasoning

The demographic association, cystic remodeling, and lesional cell phenotype form the discriminating pattern.

Slide 40 · Inflammatory myofibroblastic tumor: Who is affected?

IMT is rare and occurs more frequently in children.

The source reports an approximately equal male-to-female ratio.

A pediatric lung mass may therefore be mesenchymal rather than epithelial in lineage.

Rounded pulmonary nodule

Schematic — not a histologic specimen

Slide 41 · IMT: Symptomatic and asymptomatic presentations

Reported symptoms include fever, cough, chest pain, and hemoptysis.

Some lesions produce no symptoms.

The symptom profile is nonspecific; Morphology and tumor biology provide more specific information.

Clinical presentation

Symptoms or none

Morphology resolves lineage

Schematic — not a histologic specimen

Slide 42 · IMT: Radiographic appearance

Imaging typically shows a round, well-defined peripheral mass.

The radiographic form is compatible with multiple distinct tumor entities.

Imaging appearance alone cannot establish the myofibroblastic nature of the lesion.

Rounded pulmonary nodule

Schematic — not a histologic specimen

Slide 43 · IMT: Calcification is a described feature

Calcification is reported in approximately one quarter of cases.

Its presence may be a clue but is not specific for this diagnosis.

Absence of calcification does not exclude IMT.

Variable calcification

Schematic — not a histologic specimen

Slide 44 · IMT: Gross pathology

A typical lesion is firm and gray-white.

The cited size range is approximately 3–10 cm.

The gross mass is often well defined on imaging despite its complex cellular composition.

Well-defined solid mass

Schematic — not a histologic specimen

Slide 45 · IMT: Spindle-cell population

The tumor contains proliferating spindle-shaped fibroblasts and myofibroblasts.

The spindle-cell component constitutes the core mesenchymal tumor population.

Lymphocytes and plasma cells intermingle with the spindle cells.

Spindle cells + inflammatory cells

Schematic — not a histologic specimen

Slide 46 · IMT: Inflammatory cell admixture

Lymphocytes and plasma cells are admixed with the spindle-cell tumor.

The inflammatory component explains the descriptive adjective “inflammatory.”

These cells coexist with rather than replace the fibroblastic/myofibroblastic component.

Spindle cells + inflammatory cells

Schematic — not a histologic specimen

Slide 47 · Peripheral fibrosis in IMT

The described microscopic composition includes peripheral fibrosis.

Fibrosis forms part of the lesion architecture alongside spindle cells and inflammatory cells.

A single component in isolation is not the complete morphologic description.

Interstitial tissue changes

Schematic — not a histologic specimen

Slide 48 · ALK rearrangements define a molecular subset

Some IMTs have activating rearrangements of the ALK receptor tyrosine kinase gene.

ALK at chromosome 2p23.

This is a subset finding: Absence of rearrangement does not contradict the source-level diagnosis.

Genetic / molecular clue

Changes growth signaling

Explains biological subset

Schematic — not a histologic specimen

Slide 49 · ALK status links pathology to therapy

ALK rearrangement

Oncogenic kinase signaling

Potential ALK inhibitor response

The ALK alteration is actionable in some IMTs.

Sustained responses to ALK inhibitors in rearrangement-positive cases.

A therapeutic association does not imply all IMTs harbor ALK rearrangements.

Slide 50 · Distinguishing three featured lung lesions

Feature

Hamartoma

LAM

IMT

Usual pattern

Solitary nodule

Diffuse cystic remodeling

Peripheral mass

Defining element

Mesenchyme + epithelial clefts

Perivascular epithelioid cells

Spindle myofibroblasts + inflammation

Molecular clue

6p21 or 12q14–q15

TSC2 loss / mTOR

ALK rearrangement in subset

Columns summarize Robbins descriptions rather than a validated diagnostic rule.

Slide 51 · Case: A peripheral mass in a child

Clinical-pathology vignette

A child has a peripheral well-defined pulmonary mass with fever and cough. Histology shows spindle-shaped fibroblasts, plasma cells, lymphocytes, and peripheral fibrosis.

Inflammatory myofibroblastic tumor

Reasoning

The admixture of spindle cells and inflammatory cells, rather than symptoms alone, points to IMT.

Slide 52 · Mediastinal tumors can affect the lung secondarily

A tumor may arise within a mediastinal structure or represent metastasis from lung or another organ.

Such lesions may invade or compress adjacent pulmonary tissue.

An anatomic mass in the thorax is not synonymous with a primary lung tumor.

Primary lung

Mediastinal origin

Metastatic lesion

Schematic — not a histologic specimen

Slide 53 · Anterior mediastinal masses

Robbins-listed categories

Examples

Thymic

Thymoma

Germ cell

Teratoma

Lymphoid

Lymphoma

Endocrine

Thyroid lesions; parathyroid tumors

Secondary

Metastatic carcinoma

Compartmental lists reproduce the textbook grouping without frequency estimates.

Slide 54 · Middle mediastinal masses

Robbins examples

General type

Bronchogenic cyst

Developmental cyst

Pericardial cyst

Cystic lesion

Lymphoma

Lymphoid neoplasm

Slide 55 · Posterior mediastinal masses

Robbins examples

General type

Schwannoma; neurofibroma

Neurogenic tumors

Lymphoma

Lymphoid neoplasm

Metastatic tumor

Most from lung, per Robbins

Bronchogenic cyst

Cystic lesion

Gastroenteric hernia

Non-neoplastic mass mimic

Slide 56 · A compartment-based way to read mediastinal masses

Anterior, middle, and posterior distributions have different typical lists.

The compartment suggests a differential; It does not establish a diagnosis.

Compression and invasion can generate pulmonary effects without pulmonary origin.

Anterior

Middle

Posterior

Schematic — not a histologic specimen

Slide 57 · Case: A posterior mediastinal mass

Clinical-pathology vignette

A posterior mediastinal mass abuts the lung. The radiology report describes lung compression, but the lesion is centered outside the pulmonary parenchyma.

Start with a mediastinal differential

Reasoning

Neurogenic tumors, lymphoma, metastases, bronchogenic cyst, and gastroenteric hernia for this compartment.

Slide 58 · The lung is a common destination for metastasis

The lung as the most common site of metastatic neoplasms.

Both carcinomas and sarcomas from sites throughout the body may spread to lung.

The pulmonary lesion may therefore be secondary despite its intraparenchymal position.

Lung site

Schematic — not a histologic specimen

Slide 59 · Routes by which tumors reach the lung

Hematogenous

Lymphatic

Direct continuity

Bloodborne and lymphatic dissemination account for many distant pulmonary deposits.

Direct continuity is also possible from structures adjacent to lung.

Routes of spread help explain why the appearance of secondary tumors varies.

Slide 60 · Direct extension into lung

Esophageal carcinoma is a named example of direct pulmonary invasion.

Mediastinal lymphoma may also extend directly into the lung.

Direct extension differs anatomically from a separated intrapulmonary metastatic nodule.

Primary lung

Mediastinal origin

Metastatic lesion

Schematic — not a histologic specimen

Slide 61 · Multiple cannonball nodules: A classic pattern

The usual described pattern consists of multiple discrete nodules in all lobes.

Nodules particularly favor the lung periphery.

“Cannonball” is a morphologic descriptor, not a designation of a specific primary tumor.

Multiple discrete deposits

Schematic — not a histologic specimen

Slide 62 · Pulmonary metastases may be solitary

A solitary lung nodule is among the metastatic patterns explicitly described.

Consequently, solitary morphology cannot by itself establish primary pulmonary origin.

The pattern must be considered alongside clinical and pathologic context.

Rounded pulmonary nodule

Schematic — not a histologic specimen

Slide 63 · Endobronchial and pleural metastases

Secondary tumors may involve endobronchial surfaces.

Pleural involvement is another recognized pattern.

These locations differ from multiple round parenchymal nodules and may coexist with them.

Endobronchial involvement

Schematic — not a histologic specimen

Slide 64 · Pneumonic consolidation as metastatic pattern

Metastatic tumors can sometimes produce a consolidation-like lung appearance.

The text identifies this as an alternative to nodular patterns.

A pneumonia-like pattern therefore is not restricted to non-neoplastic processes.

Consolidation pattern

Schematic — not a histologic specimen

Slide 65 · Lepidic growth is not uniquely primary

Occasional metastases show lepidic growth resembling pulmonary adenocarcinoma in situ.

This growth pattern may occur alongside several metastatic distributions.

Architectural resemblance should not be treated as proof of primary lung origin.

Schematic — not a histologic specimen

Slide 66 · Metastatic patterns listed by Robbins

Distribution pattern

Textbook description

Multiple peripheral nodules

Typical cannonball pattern across lobes

Solitary nodule

One discrete secondary deposit

Endobronchial

Tumor involving bronchial lumen or wall

Pleural

Secondary pleural involvement

Pneumonic

Consolidation pattern

Lepidic

Occasional surface-spreading growth resembling adenocarcinoma in situ

Patterns are alternatives and may occur in combination.

Slide 67 · Case: Multiple peripheral rounded nodules

Clinical-pathology vignette

An adult with a known malignancy has numerous well-circumscribed nodules scattered through both lungs, especially peripherally.

Metastatic disease is a central consideration

Reasoning

The distribution matches the “cannonball” pattern; Morphology does not identify the original cancer.

Slide 68 · Case: A deceptively solitary pulmonary deposit

Clinical-pathology vignette

A lung biopsy from a solitary nodule shows malignant cells, and the clinical history includes a previous extrathoracic neoplasm.

Primary versus metastatic origin remains a key question

Reasoning

A solitary nodule is explicitly included among metastatic distributions and cannot settle origin alone.

Slide 69 · Integrative comparison of pulmonary tumor patterns

Pattern

Featured association

What it does NOT establish

Rounded, well-circumscribed nodule

Hamartoma or IMT

Specific lineage without histology

Cystic diffuse remodeling

LAM

A solitary solid tumor

Multiple peripheral nodules

Metastatic deposits

Identity of the primary cancer

Mediastinal-centered mass

Compartment-specific masses

Primary intrapulmonary origin

This is a teaching synthesis of source statements, not an independent diagnostic algorithm.

Slide 70 · Principal clinicopathologic lessons

Pulmonary hamartoma: Clonal mesenchymal neoplasm with entrapped epithelial clefts.

LAM: Perivascular epithelioid proliferation, TSC2–mTOR dysregulation, and cystic remodeling.

IMT: Spindle myofibroblasts with inflammatory cells; ALK rearrangement in a subset.

Secondary pulmonary lesions may appear nodular, endobronchial, pleural, pneumonic, or lepidic.

Solitary nodule / mass

Diffuse cystic process

Secondary lung deposits

Schematic — not a histologic specimen

Slide 71 · Reference and source boundaries

Primary content: Robbins, Cotran & Kumar, Pathologic Basis of Disease, 11th ed. (2026), Chapter 15, pp. 659–660.

Metastatic Tumors is included because it is grouped with this teaching unit in the supplied topic register.

Source was provided as a Markdown extraction; the original chapter PDF and source figures were not available for direct verification.

All displayed conceptual illustrations are native, editable PowerPoint schematics; they are not pathology specimens.