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Central Type of Lung Cancer: Specimen Identification & Pathology

Overview

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1. Squamous Cell Carcinoma - The Archetypal Central Tumor

Gross Specimen Identification

• Arises in major bronchi (main or lobar) - Panel D in the image below shows the classic appearance
• Gray-white firm mass at the hilum invading contiguous parenchyma
• Often causes bronchial obstruction - leading to distal atelectasis, obstructive pneumonia, or abscess
• Large lesions undergo central necrosis - creating cavitation (seen on imaging)
• First spreads to local hilar lymph nodes, then mediastinal nodes; distant spread is later than other types

Histological Identification

• Keratin pearls (concentric whorls of keratinized cells) - Panel C below
• Intercellular bridges (desmosomes) between cells - arrows in Panel C
• Ranges from well-differentiated (prominent keratinization) to poorly differentiated (minimal squamous features)
• Precursor lesion: squamous metaplasia → dysplasia → carcinoma in situ over years - detectable by sputum cytology early on

Immunohistochemistry (IHC)

• p40, p63 (squamous markers) - positive
• CK5/6 - positive
• TTF-1 - negative (distinguishes from adenocarcinoma)

Key Association

• Strongly associated with cigarette smoking (male predominance)
• Paraneoplastic hypercalcemia via PTH-related peptide secretion

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2. Small Cell Carcinoma - The Other Central Type

Gross Specimen Identification

• Pale gray, centrally located mass extending into lung parenchyma
• Typically hilar/perihilar mass with mediastinal widening
• Virtually always has hilar and mediastinal lymph node metastases at diagnosis
• Surgical resection is rarely indicated - disease is essentially always systemic at presentation

Histological Identification (Panel F below)

• Cells are small, round to fusiform, with:
  • Scant cytoplasm
  • Finely granular chromatin ("salt-and-pepper" pattern)
  • Indistinct nucleoli
  • Cells arranged in diffuse sheets
• Numerous mitotic figures and extensive necrosis
• Azzopardi effect (also called Azzapardi): blue basophilic encrustation of vascular walls from DNA released by necrotic tumor cells - a hallmark feature
• Crush artifact in small biopsies (cells are very fragile)

Immunohistochemistry

• Neuroendocrine markers: Synaptophysin, Chromogranin A, CD56 - positive
• Ki-67: Very high (>80%) - reflects high proliferative rate
• TTF-1 - often positive (~90%)
• Epithelial markers (EMA, cytokeratin) - positive

Key Molecular Features

Paraneoplastic Syndromes (SCLC)

• SIADH - from ADH/vasopressin secretion
• Cushing syndrome - ACTH secretion
• Lambert-Eaton myasthenic syndrome - autoantibodies against voltage-gated calcium channels
• Gastrin-releasing peptide, calcitonin also secreted

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Classic Pathology Image (Robbins)

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Quick Comparison: Central vs. Peripheral

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Specimen Workup for Central Lung Cancer

1. Bronchoscopy + biopsy - first-line for central lesions (direct visualization)
2. Bronchial washings / brushings / BAL - cytology for central airway tumors
3. Sputum cytology - useful for squamous cell carcinoma (central, exfoliating cells)
4. EBUS-guided TBNA - for hilar/mediastinal nodal staging
5. Resection specimen - lobectomy/pneumonectomy; gross exam identifies the bronchial involvement, nodal status

Source: Robbins & Kumar Basic Pathology, pp. 485-490 (Fig. 11.44, Table 11.6)

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Miliary TB & Bronchiectasis: Specimen Identification & Pathology

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PART 1: MILIARY TUBERCULOSIS

What is "Miliary" TB?

Pathogenesis - How Miliary TB Occurs

1. Progressive primary TB - organisms drain through lymphatics → enter venous blood → recirculate to lung via pulmonary arteries
2. Progressive secondary (reactivation) TB - erosion of a cavity into a blood vessel seeds the systemic circulation

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Gross Specimen Identification

Key gross feature: Unlike secondary (postprimary) TB which concentrates at lung apices, miliary foci are randomly distributed throughout the entire lung - upper, middle, and lower lobes equally involved.

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Microscopic/Histological Identification

Histological Components of Each Miliary Focus:

1. Central caseous necrosis - pink, granular, cheese-like, acellular core
2. Epithelioid macrophages - elongated, activated macrophages surrounding the necrotic center
3. Langhans giant cells - multinucleated giant cells with nuclei arranged in a horseshoe/peripheral pattern at the granuloma periphery
4. Lymphocytic cuff - outer rim of lymphocytes
5. Fibroblastic rim - peripheral fibrosis in healing lesions

Special Stains

• Ziehl-Neelsen (ZN) / Kinyoun stain - acid-fast bacilli stain red against a blue background
• Bacilli are most numerous in the early exudative and caseous phases but too few to find in late fibrocalcific stages
• In immunocompromised: AFB are abundant but granulomas are absent

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Systemic Miliary TB - Organ Distribution

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PART 2: BRONCHIECTASIS

Definition

Pathogenesis

1. Impaired airway defense (mucociliary clearance failure, immune deficiency) → bacterial colonization
2. Chronic infection → recruitment of neutrophils and macrophages
3. Proteolytic and oxidative enzyme release (from both bacteria and inflammatory cells) → destruction of smooth muscle and elastic tissue
4. Fibrous replacement → permanent dilation
5. Bronchial hypervascularity - bronchial arteries hypertrophy; abnormal bronchial-pulmonary arterial anastomoses form (basis of massive hemoptysis)

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Gross Specimen Identification

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Three Morphological Types (Gross & Radiological Classification)

Saccular type is the most common after bronchial obstruction or infection.

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Microscopic/Histological Identification

1. Bronchial wall destruction - loss of smooth muscle, elastic tissue, cartilage
2. Chronic transmural inflammation - neutrophils, lymphocytes, plasma cells throughout bronchial wall
3. Luminal exudate - purulent material (neutrophils, bacteria, debris) filling lumen
4. Fibrosis - replaces destroyed muscular/elastic components
5. Goblet cell metaplasia - excessive mucus secretion
6. Bronchial artery hypertrophy - increased submucosal vascularity, anastomotic channels
7. Squamous metaplasia of bronchial epithelium in chronic disease

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Causes Affecting Specimen Distribution

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Comparison Summary

Sources: Robbins & Kumar Basic Pathology, pp. 476-478 (TB morphology, miliary TB); Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 353-354 (miliary TB); Schwartz's Principles of Surgery, 11th Ed., pp. 2332-2334 (bronchiectasis morphology)

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PART 1: BREAST CARCINOMA - Specimen Identification & Pathology

Gross Specimen Identification

Key gross teaching point: In scirrhous (hard) carcinoma, the breast may be shrunken and drawn in toward the growth. Pulling at the breast produces dimpling or puckering - this is due to tumor infiltration shortening Cooper's suspensory ligaments.

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Histological Grading (Nottingham Histologic Score)

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Histological Types

1. Invasive Carcinoma of No Special Type (NST) / Invasive Ductal Carcinoma (IDC)

• Most common (~70-80%)
• Haphazard stromal invasion
• Exuberant desmoplastic response (dense fibrous stroma) - Panel C in Fig. 23.20 above
• Variable tubule formation depending on grade

2. Special Histological Subtypes

ILC key feature: Loss of E-cadherin expression (CDH1 gene mutation) - single cells cannot adhere; also predisposes to signet ring carcinoma of stomach.

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Immunohistochemistry (IHC) - Receptor Status

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Spread of Breast Carcinoma

• Lymphatic: Axillary nodes (most common) → supraclavicular nodes → Virchow node (left); internal mammary nodes
• Hematogenous: Lung, liver, bone (especially axial skeleton), brain, adrenal glands
• ILC-specific spread: Peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries, uterus

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PART 2: PEPTIC ULCER - Specimen Identification & Pathology

Definition

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Gross Specimen Identification

Sites

• Proximal duodenum (most common, 4x more than stomach) - within a few cm of the pyloric valve, anterior duodenal wall
• Gastric - lesser curvature at the junction of body and antrum

Gross Features

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Microscopic/Histological Identification

Four Layers (Surface to Depth)

• Endarteritis obliterans: Larger vessels in the scarred base are thickened with narrowed lumen - and may be thrombosed (cause of hemorrhage)
• Radiating mucosal folds: Scarring draws surrounding mucosa into folds that radiate outward (visible on gross and endoscopy)
• Foveolar metaplasia: Gastric-type cells in duodenal ulcers (protective response)
• H. pylori: Identifiable in superficial mucous layer with Giemsa, Warthin-Starry silver stain, or immunohistochemistry - comma/S-shaped organisms
• Perineural inflammation: Chronic inflammatory cells around nerves (contributes to pain)

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Benign vs. Malignant Ulcer - Key Differentiation

Clinical pearl: All gastric ulcers require biopsy from the edge (4-quadrant + base) to exclude malignancy. Duodenal ulcers are almost never malignant and do not routinely require biopsy.

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Complications of Peptic Ulcer Disease

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Quick Comparison Summary

Sources: Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 978-979 (Figs. 23.20-23.21), pp. 717-718 (Fig. 17.17); Robbins & Kumar Basic Pathology, pp. 555-556 (Fig. 13.15)