Table 1 Clinicopathological features of ALK-positive histiocytosis
From: Multisystem ALK-positive histiocytosis: a multi-case study and literature review
Subjects | Case 1 | Case 2 | Case 3 | Case 4 |
|---|---|---|---|---|
Clinical features | ||||
Gender/Age | M/38 y | F/51 y | M/32 y | M/17 mo |
Organ involved | Lung, mediastinum, LN | Brain, lung, LN | Liver, gallbladder, skin, lung, pancreas, kidney, LN | Brain, lung, liver, skin |
Size of major lesions | Lung, 5.5 × 5 cm | Brain, 2.5 × 2 cm | Numerous small nodules (≤ 1.0 cm) | Brain, 5.1 × 3.6 cm |
Symptoms | Dry cough | Numbness in the left upper limb | Abdominal pain, skin pimple | Weight loss, unable to walk |
Hepatosplenomegaly |  −  |  −  |  −  |  −  |
Hematologic abnormalitya |  −  |  −  |  −  |  −  |
Morphology features | ||||
Growth pattern | Diffuse | Nodular | Diffuse | Diffuse |
Histiocytes | Pleomorphic large cells, variable in size | Monomorphic large cells with epithelioid features | Monomorphic medium − sized cells | Monomorphic large cells with epithelioid features |
Touton giant cells |  +  |  + , few |  +  |  + , few |
Foamy cells |  +  |  +  |  + , many |  + , many |
Emperipolesis |  −  |  + , few |  −  |  −  |
Mitosis | Easily identified, 2 ~ 3/10 HPF |  < 1/10 HPF |  < 1/10 HPF |  < 1/10 HPF |
Interstitial fibrosis |  −  |  −  |  +  |  −  |
Other cells in the stroma | SL, PC | SL, PC, EP | SL, PC, FB | SL, PC |
Immunohistochemical features | ||||
ALK1, Staining pattern |  + , Diffuse strong cytoplasmic; membranous |  + , Diffuse moderate cytoplasmic; membranous |  + , Diffuse moderate cytoplasmic |  + , Diffuse strong cytoplasmic |
CD68 |  +  |  +  |  +  |  +  |
CD163 |  +  |  +  |  +  |  +  |
S − 100 |  −  |  + , weak |  −  |  −  |
CD1a |  −  |  −  |  −  |  −  |
Langerin |  −  |  −  |  −  |  −  |
P63 |  + , p | ND | ND | ND |
Ki-67 | 30% | 1% | 1% | 5% |
Others (negative) | CD20, CD3, CD30, CD45, CD79a, CK, CK8/18, CK7, CK-H, Desmon, EMA, Napsin A, PAX-5, PLAP, TTF1, SALL4, SMA, WT1 | CD3, CD20, CD21, CD23, CD35, CD4, CD8, CK, EMA; GFAP, PR, SSTR2, TTF1,WT1 | CD20, CD3, CD30, CK, Desmin, IgG4, SMA | CD20, CD3, CD30, EGFR, PLAP, SALL4, SSTR2, TdT |
ALK-FISHb |  +  |  +  |  +  |  +  |
Gene alteration | EML4-ALK(E19:A20) and TP53 mutation | KIF5B-ALK(K24:A20) | VRK2-ALK(V11:A20) and DCTN1-ALK(D26:A20) (liver biopsy specimen) | Â KIF5B-ALK(K24:A20) |
Treatment | Chemoradiotherapy followed by inhibitor (alectinib and lorlatinib) | Surgical resection followed by inhibitor (alectinib) | Alectinib | Surgical resection followed by chemoradiotherapy and ALK inhibitor (crizotinib) |
Follow-up | Stable disease for 24Â months, and then progressive disease (2mo) | Alive with regressive disease (24 mo) | Alive with regressive disease (31 mo) | Died of disease (8 mo) |