Table 2 Differential diagnosis of malakoplakia and ALK-positive histiocytosis

Age of onset

Predominantly of adults

Predominantly of young age

Site of disease

Systemic or localized disease.

Systemic disease involved multiple organs.

Localized disease commonly affects urogenital tract and gastrointestinal tract.

Systemic or localized disease.

Systemic disease tended to be young children, presented with hepatosplenomegaly, anemia and thrombocytopenia.

Localized disease tended to be older, presented with tumors in the following sites: nasal skin, intracranial cavernous sinus, foot and breast.

Histologic features

Sheets of histiocytes with poor intercellular adhesion, with Michaelis–Gutmann bodies present in both the intracellular and extracellular interstitium.

Extensive histiocytosis with irregularly folded nuclei, fine chromatin, and abundant eosinophilic cytoplasm, sometimes with emperipolesis.

Immunohistochemistry

Rarely positive for ALK.

Positive for histiocytic markers (CD68, CD163).

Negative for CD1a, CD207, BRAF-V600E.

Always positive for ALK.

Positive for histiocytic markers (CD68, CD163).

Negative for CD1a, CD207, BRAF-V600E.

Molecular pathology

No ALK fusion gene.

Frequent presence of KIF5B::ALK gene fusion, a few cases presence of COL1A2::ALK gene fusion.

Treatment

The antibiotics is an effective treatment option.

The ALK inhibitor crizotinib is an effective treatment option.