This document describes pulmonary hyalinizing granuloma, a rare lung disease of unknown etiology characterized by multiple bilateral nodular lesions seen on CT scan. Microscopically, the lesions are formed of thick collagen bundles that replace lung tissue in a storiform or whorled pattern. There is a surrounding lymphoplasmacytic inflammatory infiltrate and giant cells may be seen. It must be differentiated from other nodular lung lesions such as nodular amyloidosis or light chain deposition disease. The name is a misnomer as it is a sclerosing lesion rather than a true granuloma.

1. FLASHPATH
H A Z E M A L I

2. PULMONARY
HYALINIZING
GRANULOMA
H A Z E M A L I

3. CLINICAL
• Rare disease
• Unknown etiology
– May be autoimmune
– May be due to pervious exposure to fungal or mycobacterial antigens
• Affect adults
• Multiple, bilateral, and nodular lesions by CT
• Also associated with:
– Sclerosing mediastinitis
– Retroperitoneal fibrosis

4. GROSS
Nodules:
• Circumscribed
• Multiple, Bilateral
• Peripheral (subpleural)
• Mean size 3 cm
• Rubbery grayish-white

5. MICROSCOPIC
Nodular lesions:
• Formed of thick (keloid-like) collagen bundles
– Totally replace the lung tissue
– Arranged in storiform, whorls, donuts-like
• Inflammatory infiltrate
– Lymphoplasmacytic cells - Giant cells may be seen
– Forming a peripheral rim
– Sparse inflammatory cells may be seen within the lesion
No epithelioid macrophages
– not a typical granuloma = misnomer
No necrosis

6. CYTOLOGY
• Scattered bundles of dense acellular collagen
• variable background of lymphoplasmacytic cells

7. SPECIAL STUDIES
Negative Congo red stain:
• To differentiate it from nodular amyloidosis

8. DIFFERENTIAL DIAGNOSIS
Other hyalinized nodular lung lesions:
• Nodular amyloidosis:
– Congo red stains for apple-green birefringence
• Nodular light chain deposition disease:
– Seen mainly in patients with lymphoma, leukemia, plasma cell dyscrasia
– Consist of immunoglobulin light chains (most commonly kappa type)
• IgG4-related lung disease:
– More lymphoplasmacytic inflammatory infiltrate
– Characteristic phlebitis
– Characteristic elevated peripheral blood IgG4 levels

9. DIFFERENTIAL DIAGNOSIS
Inflammatory myofibroblastic tumors
• Solitary nodule
• More cellular than hyalinizing granuloma

10. DIFFERENTIAL DIAGNOSIS
G e n e r a l C a t e g o r i e s of G r a n u l o m a s
Classic
(Non-
necrotizing)
Necrotizing
Caseating Necrobiotic Suppurative
Non-classic

11. DIFFERENTIAL DIAGNOSIS
1. Classic (non-necrotizing):
• Round aggregate of histiocytes
– Abundant cytoplasm (epithelioid)
– Indistinct cell borders (syncytial growth)
• Giant cells are usually (but not always) present
• Examples:
– Foreign body or particles (suture, beryllium)
– Sarcoidosis
– Infection (some cases are non-necrotizing)
– Autoimmune (Crohn’s, hypersensitivity pneumonitis, primary biliary cirrhosis)
– Drug reactions
– Chronic granulomatous disease (rare)
Better to called it granulomatous
inflammation (rather than granuloma) if
syncytial aggregates of
histiocytes/giant cells are in sheets
(rather than in a discreet nodule)

12. DIFFERENTIAL DIAGNOSIS
2. Caseating granuloma:
• Caseating:
– Cheese-like appearance
– Macroscopic term only
• Necrotizing:
– Microscopic counterpart to “caseating”
• Examples:
– Infection (TB, fungus)
– Sarcoidosis (minimal necrosis is allowed)
– Necrobiotic granulomas (see later)

13. DIFFERENTIAL DIAGNOSIS
3. Suppurative granuloma:
• Granulomas with central collections of neutrophils
• Also called “ stellate microabscesses “
• Examples:
– Cat scratch disease (Bartonella henselae)
– Lymphogranuloma venereum (Chlamydia trachomatis)
– Tularemia
– Yersinia
• You should rule out Mycobacteria, Fungi at first

14. DIFFERENTIAL DIAGNOSIS
4. Necrobiotic granuloma:
• Granulomas with central nuclear (karyorrhectic) debris
– Resulted from degenerated neutrophils and/or degenerated collagen
– Appear as Blue-red granular necrosis
– In dermatopathology cases, it may appear bluish “degenerated” collagen, without
prominence of nuclear debris
• Macrophages at the periphery have elongated
nuclei that are palisaded (parallel to each other)
– Called “ palisading granulomas “

15. DIFFERENTIAL DIAGNOSIS
4. Necrobiotic granuloma:
• Examples:
– Rheumatoid nodule
– Post-transurethral resection granuloma (prostate, bladder)
– Wegener’s granulomatosis
– Granuloma annulare (central mucin)
– Necrobiosis lipoidica (shins; cake-like horizontal layers)
Granulomaannulare
Necrobiosislipoidica

16. DIFFERENTIAL DIAGNOSIS
5. Non-classic granulomas:
• Either a “misnomer”
– E.g. clinical term of “nodule/mass”, applied by non-pathologists
• Or Not strictly follow the “classic definition” of granulomas
– E.g. lesions where histiocytes are present but are not prominent
• Examples:
– Plasma cell granuloma (lung) = Inflammatory myofibroblastic tumor
– Eosinophilic granuloma (lung) = Langerhans cell histiocytosis
– Pulmonary hyalinizing granuloma = sclerosing lesion analogous to sclerosing mediastinitis
– Pyogenic granuloma = Lobular capillary hemangioma
– Lethal midline granuloma = NK/T lymphoma nasal type

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