Normal benign elements

• Bronchial cells
  • Columnar cells
  • Small nuclei
  • Abundant apical cytoplasm
  • Terminal bars and cilia frequent and prominent
• Alveolar macrophages
  • Round cells with pale, irregular nuclei
  • Abundant, foamy cytoplasm
• Pneumocytes (Diagn Cytopathol 2010;38:297)
  • Appear similar to alveolar macrophages
  • Few cohesive groups with scalloped borders, intercellular windows or gaps

Reactive elements

• Basal cell hyperplasia (Diagn Cytopathol 2010;38:297)
  • Small, uniform cells
  • Dark round or oval nuclei, smooth nuclear borders
  • Scant basophilic cytoplasm
  • Occasional molding; can mimic small cell carcinoma
• Squamous metaplasia (Diagn Cytopathol 2011;39:144)
  • Smudgy chromatin
  • Eosinophilic cytoplasm versus organophilic
  • Preserved N:C ratio
• Creola bodies (Arerugi 1989;38:542)
  • Clusters of ciliated bronchial epithelial cells
  • Associated with asthma and eosinophils
• Curschmann spirals (Diagn Cytopathol 1998;19:349)
  • Spiral shaped mucous plugs
  • Nonspecific finding: can be seen in smokers, lung cancer, chronic bronchitis
• Treatment effect: radiation therapy (Pathologica 1991;83:317)
  • Clinical context is helpful in this diagnosis
  • Atypical nuclei with smudgy effect
  • Abundant cytoplasm, often vacuolated
• Anthracosis
  • Dark pigment within macrophages
  • Finer than melanin

Infection

• Bacterial
  • Actinomycosis (Monaldi Arch Chest Dis 2022;92:1641)
    • Dark cotton ball-like mass
    • Spider leg-like projections
    • Branches at acute angles
    • Sulfur granules
  • Nocardiosis (Diagn Cytopathol 2017;45:1105)
    • Narrower than Actinomyces
    • Right angle branching
    • Associated with neutrophils
  • Tuberculosis (Diagn Cytopathol 2014;42:993)
    • Strongly associated with necrotizing granulomas
    • Acid fast positive
• Fungal
  • Blastomycosis (Acta Cytol 2020;64:532)
    • Thick walled, double contoured spores (8 - 15 μm)
    • Broad based bud
  • Histoplasmosis (Acta Cytol 2020;64:532)
    • Histiocytes filled with small spores (2 - 4 μm)
    • Narrow based budding with capsule
  • Pneumocystis (Cancer Cytopathol 2018;126:643)
    • Curved, cup shaped cysts (4 - 8 μm)
    • Central dot with GMS staining
    • Associated with frothy pink exudates
  • Aspergillus (Cancer Cytopathol 2018;126:643)
    • Septate hyphae
    • 45 degree acute angle branches
    • Background often has abundant neutrophils and necrosis
  • Cryptococcosis (Acta Cytol 2020;64:532)
    • Narrow based budding (4 - 12 μm)
    • Mucin rich capsule
    • Positive for mucicarmine
  • Coccidioidomycosis (Semin Diagn Pathol 2017;34:530)
    • Thick walled, large spherules (10 - 80 μm)
    • Can be filled with endospores
  • Mucormycosis (Semin Diagn Pathol 2017;34:530)
    • Exclusively in diabetic or immunocompromised patients
    • Broad hyphae with thin walls
    • Twisted and folded walls
    • Irregular branching
  • Candida (Semin Diagn Pathol 2017;34:530)
    • Can occur as endobronchial growth or in abscess
    • Oval yeasts
    • Pseudohyphae: elongated and pinched at attachment
• Viral cytopathic effects
  • Cytomegalovirus (Cancer Cytopathol 2018;126:643)
    • Nuclear enlargement with owl eye nucleoli
      • Intranuclear inclusion with surrounding halo
  • Adenovirus (Diagn Cytopathol 2017;45:614)
    • Smudged nuclei
    • Intranuclear basophilic inclusions surrounded by a small halo
  • Herpes (Cancer Cytopathol 2018;126:643)
    • Triad: multinucleation, margination, molding
    • Can have significant acute inflammation and necrosis
• Parasitic infections
  • Strongyloidiasis (Cancer Cytopathol 2018;126:643)
    • Larval form in lung: filariform
    • May be present in sputum
  • Echinococcus (Paediatr Respir Rev 2022;43:11)
    • Thick walled hydatid cyst
    • 2 layers: outer PAS positive layer and endocyst layer
    • Inner layer shows protoscoleces (2 circular rows of hooklets and suckers)

Benign neoplasms

• Hamartoma (Diagn Cytopathol 2011;39:144)
  • Can have varying proportions of epithelial cells and mesenchymal tissue
  • Recognition of cartilage and fibromyxoid stroma is key to diagnosis
• Meningioma (Acta Cytol 1998;42:1424, Neurosurg Rev 2022;45:2671)
  • Spindled shaped cells with elongated or fusiform nuclei
  • Arranged in parallel or whorled formations
  • Psammoma bodies
  • Positive IHC: EMA, vimentin, SSTR2
  • Negative IHC: S100
• Granular cell tumor (Int J Clin Exp Pathol 2014;7:5186)
  • Polygonal cells with eccentric nuclei
  • Eosinophilic granular cytoplasm
  • Indistinct borders
  • Positive IHC: S100
• Endobronchial lipoma (Ther Adv Respir Dis 2014;8:162)
  • Abundant adipose tissue
  • Typically polypoid and smooth on bronchoscopy
• Langerhans cell histiocytosis (N Engl J Med 2022;387:2449)
  • Langerhans cells
    • Foamy cytoplasm, large coffee bean shaped nuclei
    • Positive IHC: S100, CD1a
  • Eosinophils

Contributed by Xiaobing Jin, M.D., Ph.D. and Heather I-Hsuan Chen-Yost, M.D.



Images hosted on other servers:

• Lung, right upper lobe, fine needle aspiration:
  • Negative for carcinoma
  • Granulomatous inflammation present

• Lung, left upper lobe, bronchoalveolar lavage:
  • No malignant cells identified
  • Predominately pulmonary macrophages and chronic inflammation
  • Type of specimen:
    • Bronchial wash and brush right lower lobe
  • Clinical and imaging information
    • Irregular 50 mm solid mass right lower lobe. Presented with right lower lobe pneumonia. Immunocompromised patient.
  • Diagnostic summary
    • Specimen 1
      • Bronchial wash right lower lobe bronchus
      • Category: benign
      • Diagnosis: acute inflammation
    • Specimen 2
      • Bronchial brush right lower lobe bronchus
      • Category: benign
      • Diagnosis: acute inflammation with fungi (see report below)
  • Macroscopic description
    • Specimen 1: bronchial wash right lower lobe bronchus: 5 mL grey viscous fluid
    • Specimen 2: bronchial brush right lower lobe bronchus: 2 alcohol fixed direct smears
  • Microscopic description
    • Specimen 1: Pus is present with plentiful neutrophils, macrophages and debris as well as a small number of bronchial cells. Ziehl–Neelsen stain for mycobacteria is negative and PASD for fungi is negative.
    • Comment: Acute inflammation is present. Correlation with microbiological studies is required.
    • Specimen 2: Tissue fragments of bronchial cells, macrophages and neutrophils are present, with necrotic debris. The Giemsa and PASD show aggregates of fungi with acutely branching hyphae, confirmed in the Grocott methenamine silver stain, which shows septa, suggestive of Aspergillus spp.
    • Comment: Correlation with microbiological studies and imaging is required.
  • Editorial note
    • There is a mass lesion in the lung. The bronchial washing and bronchial brushing show acute inflammatory changes and some cytopathologists may prefer to use the category nondiagnostic for this, despite the presence of the fungal elements suggesting a possible aspergilloma. Correlation with clinical and imaging findings is required.

• Lung, right lower lobe, fine needle aspiration:
  • Adipose, cartilage and benign reactive bronchial cells (see comment)
  • No malignant cells identified
  • Comment: The combination of these findings is suggestive of a hamartoma but clinicoradiographic correlation and surgical biopsy are recommended for definitive diagnosis.
  • Type of specimen
    • Endobronchial ultrasound guided FNAB of left upper lobe lung
  • Clinical and imaging information
    • 20 mm solid rounded mass left lower lobe of lung. Presented with wheeze and history of previous pneumonia.
  • Diagnostic summary
    • Endobronchial ultrasound guided FNAB of left upper lobe lung
    • Category: benign
    • Diagnosis: suggestive of pulmonary hamartoma
  • Macroscopic description
    • 3 air dried slides, 3 alcohol fixed slides
    • 3 mL pink normal saline needle rinsings
  • Microscopic description
    • These mildly cellular smears show fragments of myxoid stroma and chondroid material with occasional bronchial epithelial tissue fragments in a bloody background. There is no diagnostic material in the cell block.
    • Comment: The features are suggestive of a pulmonary hamartoma.

This image is from a 63 year old man who presented with a right upper lobe mass. Which of the following is the best diagnosis?

1. Atypical cells present
2. Benign: bronchial cells only
3. Benign: favor hamartoma
4. Nondiagnostic
5. Positive for non-small cell carcinoma

C. Benign: favor hamartoma. This FNA image comes from a 63 year old man who presented with a right upper lobe lobulated mass. A Diff-Quik smear shows benign, matrix-like material with adjacent chronic inflammation. This case was signed out as having neoplastic cells that are compatible with pulmonary hamartoma. Correlation with the imaging findings was helpful in rendering this diagnosis. Answers A and D are incorrect because the matrix material and adipose tissue are hallmarks for hamartoma; therefore, the categories of nondiagnostic and atypical are not appropriate in this context. Answer B is incorrect because there is an abundance of matrix material and a lack of bronchial cells. Answer E is incorrect because there are no small cell carcinoma cells in this sample.

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Reference: Cytopathology - Benign (lung)

This image is from a 35 year old woman that has a history of lung transplant and underwent a bronchial washing. Which of the following is the best diagnosis?

1. Atypical cells present
2. Benign: cytomegalovirus (CMV) present
3. Nondiagnostic
4. Positive for non-small cell carcinoma
5. Suspicious for adenocarcinoma

B. Benign: cytomegalovirus (CMV) present. This ThinPrep slide shows cells with owl eye inclusions characteristic of CMV. There is an enlarged nucleus with a surrounding halo, consistent with viral cytopathic changes of CMV. Answer A is incorrect because while the nuclei are atypically large, the nuclear halo helps with the diagnosis of CMV infection in benign cells. Answer C is incorrect because the cells present are diagnostic of CMV. Answers D and E are incorrect because the sample does not show neoplastic cells. The nuclei are enlarged but the changes seen, such as the nuclear halo and the preserved N:C ratio, are more supportive of CMV infection.

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Reference: Cytopathology - Benign (lung)

This image is from a 57 year old man that underwent a bronchial washing. Which of the following is the best diagnosis?

1. Atypical cells present
2. Benign: bronchial cells only
3. Nondiagnostic
4. Positive for metastatic colorectal adenocarcinoma
5. Positive for non-small cell carcinoma

B. Benign: bronchial cells only. The cells in the image show a low N:C ratio and are columnar. Prominent cilia are present, supporting the diagnosis of benign bronchial cells. Answer A is incorrect because the cells do not show nuclear atypia. In addition, there is appropriate N:C ratio and terminal bars with cilia. Overall, these features exclude these cells from the atypical category. Answer C is incorrect because this is a bronchial washing and the presence of bronchial cells and macrophages are considered normal elements in such a specimen. Answers D and E are incorrect because the background columnar cells show preserved N:C ratio and terminal bars with cilia. The nuclei are not overlapping. Overall, these features are diagnostic of benign bronchial cells.

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Reference: Cytopathology - Benign (lung)