pathology lung biopsy

1. SLIDE SEMINAR ON LUNG
BIOPSY
Dr. Om Jha
Pathology Resident
Shree Birendra Hospital; NAIHS
DATE: 5th June 2023

2. HISTORY
• 34 years old female, Diffuse parenchymal lung disease ? Sarcoidosis

3. INVESTIGATIONS
HRCT
1) Numerous tiny randomly distributed milliary nodules bilaterally,
Numerous tiny sand like calcifications throughout both the lungs
with sub pleural and peri bronchial distribution with immediate sub
pleural sparing. Diffuse ground glass changes bilaterally. Features
suggestive of PULMONARY ALVEOLAR MICROLITHIASIS
Differential diagnosis : Sequelae of chronic granulomatous infection
with reactivation of disease
2) Fibro-calcific changes bilaterally.
3) Few enlarged mediastinal lymph nodes

4. GROSS FINDINGS
• Received four greyish white tissue bits altogether measuring
0.3x0.2cm. AE(B1)

5. MICROSCOPIC FINDINGS

6. Section from lung biopsy shows
multiple fragmented tissue bits

7. Foci showing tissue fragment
lined by pseudostratified
columnar epithelium with
basally placed mucin

8. Dilated lung alveoli lined by
the single layer of flat
squamous epithelium

9. Alveolar spaces filled with basophilic calcific deposit

10. Basophilic calcific deposits are laminated and concentric and seen
over the pseudostratified columanar lining

11. Anthracotic pigment
seen

12. MICROSCOPIC DESCRIPTION
• Section from lung biopsy shows multiple fragmented tissue bits. One
of the foci shows tissue bit lined by pseudostratified columnar
epithelium with basally placed mucin. Another foci of tissue shows
dilated alveoi lined by single layer of flat squamous epithelium. The
dilated alveoli is filled with basophilic calcific material. Some of these
basophilic deposits are laminated and concentric. Interstitium
comprises of inflammatory infiltrated predominantly lymphocytes.
Anthracotic pigment is seen. Alveolar macrophages seen. No
granuloma seen. No evidence of malignancy seen.

13. PROVISIONAL DIAGNOSIS
1) Pulmonary alveolar microlithiasis
FAVOURING POINTS
1) Age: 34 years female (common in adult)
2) HRCT Chest : Numerous tiny sand like calcifications throughout both
the lungs with sub pleural and peri bronchial distribution
3) Histology : Alveolar spaces filled with calcific deposit
4) Lamilated and concentric calfic deposits seen.

14. DIFFERENTIAL DIAGNOSIS
1) Pulmonary blue bodies
2) Pulmonary corpora amylacea
3) Metastatic calcification
4) Heterotropic ossification

15. PULMONARY ALVEOLAR
MICROLITHIASIS
PULMONARY BLUE BODIES
1) Most are 250-270 microns 1) Most are 15-40 microns
2) Most alveoli filled 2) Usually few and scattered,
alveoli not filled
3) Autosomal recessive 3) Many cases are associated with
pneumoconiosis or interstitial lung
disease

16. Extensive Pulmonary alveolar
microlithiasis
Pulmonary Blue bodies
1.Rittayamai N, Muangman N, Ruangchira-urai R. Extensive
pulmonary alveolar microlithiasis. Respirology Case Reports.
2014;2(1):4–6.
1.Rosen Y. Pulmonary blue bodies [Internet]. [cited
2023 Jun 5]. Available from:
https://commons.wikimedia.org/wiki/File:Pulmonary
_blue_bodies_2.jpg

17. PULMONARY ALVEOLAR
MICROLITHIASIS
PULMONARY CORPORA
AMYLACEA
1) Calcified 1) Not Calcified
2) Most alveoli filled 2) Usually scattered, alveoli
not filled
3) Autosomal recessive, mean
age of symptoms 30 years
3) Increased numbers with
aging, asymptomatic

18. Extensive Pulmonary alveolar
microlithiasis
1.Gupta V, Malik S, Kalra R, Gupta S, Dalal N,
Sen R. Pulmonary Corpora Amylacea: An
incidental autopsy finding. 2018 Sep
9;6:346–8.

19. PULMONARY ALVEOLAR
MICROLITHIASIS
METASTATIC CALCIFICATION
1) Restricted to alveolar air spaces 1)May involve air spaces,
interstitium, bronchial
walls
2) Spherical and laminated 2) Irregular calcification
3) Autosomal recessive 3) Associated with renal failure,
parathyroid carcinoma

20. Pulmonary alveolar microlithiasis

21. PULMONARY ALVEOLAR
MICROLITHIASIS
HETEROTOPIC CALCIFICATION
1) Restricted to alveolar air spaces 1) Interstitial
2) Spherical and laminated 2) Lamellar spicules of bone
3) No cellular component 3) Osteocytes in lacunae
4) Autosomal recessive 4) Associated with prior
inflammation

22. PULMONARY ALVEOLAR MICROLITHIASIS
Definition : It is Autosomal recessive lung disease characterized by
filling of alveoli by calcospherites.
Diagnostic Criteria :
A) CLINICAL
• Autosomal recessive
• Caused by mutations in solute carrier family 34 member 2 (SLC34A2)
gene, which encodes the type IIb sodium-phosphate cotransporter in
alveolar type II cells, are responsible for the pathogenesis

23. • SLC34A2 serves a crucial role in the transportation of phosphate ions
from the alveolar spaces into alveolar type II cells.
• Mutations in the SLC34A2 gene that cause the dysfunction of alveolar
type II cells result in the accumulation of phosphate and the
formation of microliths in the alveolar space.

24. • Gradual onset and progression
• About half of patients are found upon screening families of patients
- Most are asymptomatic, even if the deposition is extensive
• Average age of clinical presentation around 30
- Can be found in infants
• May take decades to progress to respiratory failure
• No effective treatment except lung transplant
• Symptoms typically appear in the third or fourth decade of life and there is often
a notable dissociation between the advanced radiological findings and the mild
clinical presentation.
• In symptomatic patients shortness of breath is the most common symptom,
followed by a dry cough, chest pain, sporadic hemoptysis and asthenia

25. B) RADIOLOGY
Chest x-ray : “Sand storm” of calcified densities
Mainly in lower and mid zones
• High resolution computed tomography (HRCT) : Thickening and
calcification of pleura, interlobular septa, bronchovascular bundles
• Focal ground glass opacities and consolidation
• Subpleural cysts

26. C) GROSS EXAMINATION
• Granular and nodular pleural surface with fibrous and calcified areas
• Cut sections of the lung have a granular consistency due to extensive
round or ovoid microcalcifications that may be accentuated along
interlobular septa
• Variably sized concentrically laminated concretions are present both
in alveolar spaces and in the interstitium

27. D) HISTOPATHOLOGY
• The diagnosis can usually be made without a biopsy based on
history and radiology
• Bronchoalveolar lavage and sputum may demonstrate microliths
• Biopsy shows diffuse filling of alveolar air spaces by calcospherites
• 250-750 microns but may reach 3 mm
• Lamellated calcifications
• Principally composed of calcium and phosphate
• Late stages may show increased localization to subpleural, paraseptal and
peri-bronchovascular regions
• Fibrosis and ossification may occur in same areas

30. E) CYTOLOGY AND SPUTUM STUDIES
• Microliths may be seen in expectorated sputum or BAL samples, and
can be used to establish a definitive diagnosis in the setting of a
typical history and HRCT
• Histology demonstrating the typical lamellar structure of microliths
can help to distinguish them from other airway calculi in the
differential.

31. OTHER DIFFERENTIAL DIAGNOSIS OF OTHER
AIRWAY CALCULI
1) Curschmann's spirals, associated with asthma and chronic
bronchitis: Composed of glycoproteins and are not typically
calcified
2) Psammoma bodies: Concentric calcified laminated structures that
form within epithelial cell aggregates or small tissue fragments and
are often associated with adenocarcinoma

32. G) GENETIC TESTING
• Genetic testing on DNA from peripheral blood myeloid cells that
demonstrates damaging mutations in SLC34A2

33. THANK YOU