PMC9160658_01
Treatment timeline. The patient suffered from APH since February 2019, and diagnosed in April 2020. After diagnosed, the patient was maintained on alectinib since the 28th April 2020. PR respond reached.
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F1
The treatment timeline is shown in Figure 1.
(A) CT and MRI scan of lung and abdomen. CT and MR images showed pulmonary nodule (yellow arrow), liver, kidney and polypoid lesion of gallbladder from August 2019 to February 2021. The multinodules resolved significantly following alectinib treatment. (B) Observation of skin lesion. Before treatment, the multiskin rash and nodule were observed (yellow arrow) on chest wall, back and face; After 1 month treatment, the multiskin rash and nodule were dramatically improved. (C) Pathology. (a) Nonencapsulated gallbladder lesion (arrow) with ill defined margin (H, E, 4x). (b) Gallbladder lesion of fascicular spindle cells, foamy histiocytes and inflammatory cells (H&E, 20x). (c) adjacent to liver capsule with infiltration of the liver parenchyma (arrow) (H&E, original magnification 4x). (d) Liver lesion of numerous foamy histiocytes admixed with Touton-type giant cells (arrow), spindle cells and inflammatory cells (H&E, 20x). (e) The histiocytes had small dark nuclei to medium-sized folded vesicular nuclei with fine chromatin and small to prominent nucleoli (H&E, 40x). (f) ALK expression with a cytoplasmic staining pattern in histiocyes and Touton-type giant cells (inset). Hepatocytes (arrow) were negative for ALK (20x, inset 40x). (g) Nonencapsulated skin lesion (arrow) with ill defined margin (H&E, 4x). (h) Xanthogranuloma-like appearance of the skin lesion (H&E, 10x). (i) Classic and characteristic moderate- to large-sized foamy histocytes with folded nuclei and small to prominent nucleoli of the liver lesion. Note also a Touton-type giant cells (arrow) (H&E, 40x). (j) CD68 expression in histiocytes of the skin lesion (20x). (k) ALK expression in histocytes of the skin lesion (40x). (l) Break-apart fluorescence in situ hybridization (FISH) assay for ALK gene rearrangements showed positive result with separations of the green and red signals (arrow, 100x). (D) Routine blood test, liver function and lipase/amylase test. No severe liver function, gastrointestinal and hematological toxicity over Grade II (CTCAE 3.0) were observed. For liver function, the levels of AST, ALT, GGT, and albumin were 28 U/l (0-40 U/l), 36 U/l (0-50 U/l), 234 IU/l (<60 IU/l), and 36.2 g/l (40-55 mumol/l), respectively. For routine blood test, WBC and RBC were 7.27 x 109/l (3.6-9.5 x 109/l) and 4.48 x 1012/l (4.3-5.8 x 1012/l), respectively. For lipase/amylase test, the lipase and amylase were 151 IU/l (13-60 IU/l) and 169 IU/l (344-135 IU/l), respectively. The recurrent pancreatitis was simultaneously cured and was accompanied by lipase/amylase normalization.
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Chinese man presented with obvious pain below the xiphoid and skin rashes. CT and MRI scan revealed multiple nodules in the pulmonary system, liver, pancreas, and kidneys, and polypoid lesions of the gallbladder (Figure 2A). After cholecystectomy, recurrent pancreatitis occurred, and skin rashes in the body with multiple nodules developed (Figure 2). However, hemoglobin, white blood cells (WBCs), red blood cells (RBCs), thrombocytes (PLT), and conjugated/unconjugated bilirubin levels were normal (Figure 2). Microscopically, as shown in Figure 2C, lesions in both the gallbladder and liver were not encapsulated and had ill-defined margins. The lesion of the gallbladder and liver were shown in Figure 2Ca-c. Touton-type giant cells, lymphocytic infiltrates, eosinophils, and occasional plasma cells (Figure 2Cd). The histiocytes had small dark nuclei to medium-sized folded vesicular nuclei with fine chromatin and small to prominent nucleoli (Figure 2Ce). Touton-type giant cells (Figure 2Ci), similar to those seen in the liver and gallbladder lesions. The histiocytes were positive for CD68 (Figure 2Cj), CD163, and ALK (Figure 2Ck) but negative for the S-100 protein. FISH assays were positive for ALK rearrangements (Figure 2Cl). At the beginning, the patient was not provided specific treatment, which not only resulted in the rapid and continuous increase of both lesion size and the number of nodules in the involved organs (Figure 2) but also caused recurrent pancreatitis and body weight loss of approximately 15 kg. ALK inhibitor alectinib (450 mg bid) was used, then this patient was maintained on alectinib. After treatment, the multiple nodules in the pulmonary system, liver, pancreas, kidneys, as well as skin rashes were dramatically improved (Figure 2), and partial response was achieved. The recurrent pancreatitis was simultaneously cured and was accompanied by lipase/amylase normalization (Figure 2D).