ALK-positive Histiocytosis Research Articles

ALK-Positive Histiocytosis and its Distinctive Manifestation in the Breast

Abstract Introduction/Objective ALK-positive histiocytosis (APH) is a rare histiocytic proliferation disease that harbors ALK rearrangements, often involving fusion with KIF5B. Primary cases in the unilateral breast are exceptionally uncommon, with only a few reported cases globally, characterizing it as a unique histiocytic proliferation disorder. Methods/Case Report In our study, we report a case of unilateral multifocal breast involvement of ALK-positive histiocytosis following bilateral breast core biopsies in a 56-year-old Hispanic woman who presented with bilateral breast masses. Right breast imaging demonstrated multiple nodular densities, further characterized on ultrasound as a hypoechoic region of 8 cm with increased vascularity. On right breast biopsy, prominent proliferation of histiocytes (lacking high-grade cytologic atypia) with chronic inflammation, few giant cells, and focal cholesterol clefts were identified. On immunohistochemical studies, the lesional cells were variably positive for histiocytic markers CD68, CD163, and PU.1 and were negative for S100 and pancytokeratin. ALK1 showed multifocal staining in the lesional cells as confirmed on repeat study; however, ALK (D5F3), GMS and acid fast studies were negative. The presence of focal cholesterol clefts, scattered giant cells, and chronic inflammation lead us to consider aberrant ALK expression in a reactive process. However, APH was definitively diagnosed through confirmation of clonal histiocyte proliferation, observed findings on morphology, immunophenotyping, and the presence of KIF5B-ALK gene fusion as detected by comprehensive solid tumor fusion panel testing. Results (if a Case Study enter NA) NA Conclusion It is noteworthy that ALK-positive histiocytosis can occasionally present alongside features of a reactive process in the breast. Therefore, considering any history of prior surgery or trauma at the lesion site is crucial. However, we recommend a comprehensive approach in most cases, which includes morphological, immunohistochemical, and molecular analysis on all suspected histiocytosis cases. This approach aims to increase awareness and detection of this rarely described entity and to precisely distinguish it from other diseases for prognostic and therapeutic purposes.

An Anaplastic Lymphoma Kinase (ALK) Immunohistochemical Pitfall: ALK-positive Histiocytosis versus Angiomatoid Fibrous Histiocytoma

Abstract Introduction/Objective The 5th Edition WHO classification expanded the histiocytic/dendritic cell neoplasms to include ALK-positive histiocytosis, which can present as multisystem or single-site disease, affecting various age groups. These tumors lack high-grade cytologic features but express ALK by immunohistochemistry, typically indicating ALK locus rearrangements. In this case study, a cutaneous mass initially suspected as ALK-positive histiocytosis was found to be angiomatoid fibrous histiocytoma (AFH) with ALK expression, highlighting the potential diagnostic pitfall due to overlapping histomorphology and ALK expression. Methods/Case Report A previously healthy twelve-year-old boy sought evaluation for a growing and ulcerating mass on his left arm, which developed gradually over a year post-injury. Laboratory tests showed elevated inflammatory markers and mild anemia. A biopsy of the ulcer revealed Staphylococcus aureus infection. Initial histological examination revealed mixed inflammatory infiltrates with focal necrosis, prominent histiocytes, and giant cells. Despite favoring an infectious cause, immunostains were performed. AE1/AE3, ERG, CD34, CD30, S100, SOX10, SMA, and MyoD1 were negative, while INI1 was retained. However, ALK was strongly positive in some histiocytoid cells, suggesting ALK-positive histiocytosis. Surgical resection was subsequently performed to manage the abscess and characterize the lesion. Histologic examination revealed a solid nodule containing spindled and epithelioid cells with a bland histiocytoid appearance, arranged in a compact syncytial growth pattern within the dermis and subcutis. Surrounding the tumor, there was a distinct cuffing of fibrosis with organized lymphoplasmacytic cells. Break apart fluorescence in situ hybridization studies showed rearrangement of EWSR1 but not ALK. The diagnosis of angiomatoid fibrous histiocytoma was rendered. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of understanding immunohistochemical features, especially those that are unusual and unexpected in rare diseases. With the growing use of minimally invasive sampling techniques, this case study underscores the significance of integrating molecular diagnostics with clinical, histological, and immunophenotypic evaluations to achieve an accurate diagnosis in surgical pathology.

Multisystem ALK-Positive Histiocytosis With DCTN1::ALKFusion in an Adult, Responsive to Alectinib: Case Report and Literature Review.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

Incidentally Detected ALK-Positive Histiocytosis with EML4::ALK Fusion in a Solitary Pulmonary Nodule Following COVID-19 Infection: A Rare Case Report.

We hereby report a patient with ALK-positive histiocytosis with localized lung involvement. A 47-year-old woman presented with a solitary pulmonary nodule in the left upper lobe, 7 months after COVID infection. A well-defined 15 mm yellow mass was found in trisegmentectomy specimen. Histopathological examination revealed that the mass was composed of epithelioid and spindle cells with foamy cytoplasms. No necrosis, pleomorphism, or nuclear atypia was detected. The cells were positive for CD68, CD163, PU.1, ALK and negative for KRT, smooth muscle actin (SMA), S100, Melan-A, CD34, STAT6, and BRAF VE1. Flourescence in situ hybridization demonstrated ALK gene rearrangement, and next generation sequencing confirmed EML4::ALK fusion. Lung involvement in ALK-positive histiocytosis is characterized by the presence of pulmonary nodules, which can be seen in all forms of the disease. However, lung involvement is rarely seen in single-system ALK-positive histiocytosis. Our report represents the fourth documented instance of localized lung involvement in ALK-positive histiocytosis, an exceedingly rare occurrence, and it is the third instance with available molecular data.

ALK-positive histiocytosis in 12 Asian children

Anaplastic lymphoma kinase-positive histiocytosis, first reported in 2008, is a rare, novel type of neoplasm. To date, no more than 100 cases of anaplastic lymphoma kinase-positive histiocytosis have been reported. In this retrospective study, 12 cases of anaplastic lymphoma kinase-positive histiocytosis, including clinical symptoms, histological features, molecular pathology, treatment, and prognosis, in children were analyzed to gain a deeper understanding of the disease. All patients were Asian children, aged 2 months to 8 years and 2 months (mean 3.1 years), and the male-to-female ratio was 5:7. All patients were followed up closely. One patient died during the follow-up period, seven (case 1–7) had focal anaplastic lymphoma kinase-positive histiocytosis, and five (case 8–12) had multisystem anaplastic lymphoma kinase-positive histiocytosis. In addition, we report the case of a patient who benefited from anaplastic lymphoma kinase-targeted therapy and a patient with the rare EML4-ALK fusion gene. The current study is expected to substantially contribute to increasing the awareness of anaplastic lymphoma kinase-positive histiocytosis.

DP14 ALK-positive histiocytosis with involvement confined to the skin: report of two cases in adults

DP14 ALK-positive histiocytosis with involvement confined to the skin: report of two cases in adults

ETMR-31. A UNIQUE CASE OF CNS DIFFUSE, NON-SYSTEMIC ALK+ HISTIOCYTOSIS IN A PEDIATRIC PATIENT

Abstract BACKGROUND Histiocytic disorders are a group of rare diseases with accumulation of of macrophages, monocytes, or dendritic cells in various parts of the body. ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 that is very rarely described in pediatrics. METHODS A 20 month old male presented to an adult hospital after a prolonged period of headaches, vomiting, and loss of developmental milestones. Imaging demonstrated severe hydrocephalus and extensive thickened leptomeningeal enhacement with mass effect. He underwent VP shunt placement and revision, a T7-T10 laminectomy, and tumor debulking. Extensive molecular testing, including DNA and RNA analysis by NGS was performed and a CLTC::ALK fusion was identified, along with Tier III DNA variants, yielding a diagnosis consistent with ALK-Positive Histiocytosis, with diffusivity in the CNS system. Full evaluation demonstrated no involvement of the peripheral nervous system or other systemic involvement. He initially demonstrated signs of neuro-irritation, altered tone, and lower extremity clonus. RESULTS After review of very little literature published on similar patients, although none with a clinical picture matching his, he was started on a treatment course of high dose dexamethasone, vinblastine, and lorlatinib targeting the ALK+, likely driver, mutation of his disease. On evaluation scans two months into treatment, he showed no change in his disease burden. He was transitioned to clofarabine cycles with daily lorlatinib for continued targetted therapy. After six total cycles, he demonstrated a high partial to complete remission (allowing for evidence of scarred tissue) and tremendous neurologic and developmental milestone gains. CONCLUSIONS This case demonstrates a unique presentation in which there is little described in the literature in way of clinical features or treatment standards, and further none exactly similar to this patient. After undergoing extensive evaluation and therapy modication, he responded remarkably well and continues to have optimal quality of life.

OTHR-01. ALK-DRIVEN INFANT-TYPE HEMISPHERIC HIGH-GRADE GLIOMA AND CNS HISTIOCYTOSIS SUCCESSFULLY TREATED WITH A SECOND GENERATION ALK-INHIBITOR: MOLECULAR CHARACTERIZATION SAVES THE DAY

Abstract BACKGROUND Molecular characterization of brain tumors (BT) is increasingly becoming essential for diagnosing and managing central nervous system (CNS) tumors. Infant BT is a particular category of pediatric CNS tumors that poses a challenge to the neuro-oncologist. METHODS Here, we present two distinctive cases where molecular characterization significantly influenced diagnosis, management, and outcome. RESULTS The first case is a 2-year-old boy presented with generalized seizures. MRI of the brain showed multiple dural-based tumors. Biopsy was consistent with ALK-positive histiocytosis (KIF5B-ALK fusion). Additional lesions were detected in the right kidney and left femoral head. Despite three months of LCH-based therapy, the tumor progressed. Chemotherapy was halted, and treatment with alectinib was initiated. Follow-up MRIs after 3 and 6 months showed marked regression and a complete resolution of the lesions, respectively. The second case is a 12-month-old boy who exhibited developmental regression and increased head circumference over the past three months. MRI revealed a large complex right ventricle mass measuring 8.6x7.2x8 cm. Subtotal resection was complicated by severe intracranial bleeding, requiring prolonged intensive care stay. The initial pathological diagnosis was anaplastic ependymoma. He received two cycles of neoadjuvant chemotherapy followed by a second look surgery, which failed to achieve a gross total resection. Molecular testing by this time identified an ALK-CCDC85A fusion, altering the diagnosis to infant-type hemispheric glioma. He was started on alectinib. MRI after 3 and 6 months showed a favorable response with an overall improvement in his cognitive function. Both patients tolerated alectinib well, remaining on therapy for 6 and 12 months, respectively. No toxicities were reported. CONCLUSION These cases illustrate the transformative role of molecular characterization in managing infants with CNS tumors, highlighting its potential as a game-changer in pediatric neuro-oncology.

Ocular findings in patients with histiocytosis and association with clinical and molecular features

Background/aimsOcular manifestations of histiocytosis and their genetic underpinnings are poorly characterised. This study characterises ocular sites of histiocytosis, notate genetic alterations and correlates to histiocytosis clinical features including subtype and...

ALK positive histiocytosis with multiple system involvement: report of a case

ALK positive histiocytosis with multiple system involvement: report of a case

Imaging features of ALK-positive histiocytosis with neurological involvement: a case report and literature review.

ALK-positive histiocytosis is an exceptionally rare neoplasm of histiocytes that predominantly involves the nervous system and can also affect the skin and other parts of the body. Previous relevant literature has provided limited information regarding the imaging manifestations of this disease with neurological involvement. We reported a case of ALK-positive histiocytosis with multisystem involvement. Together with a comprehensive literature review, the imaging characteristics of this disease in the nervous system were summarized. A 3-year-old girl with abdominal pain and ambulation difficulty checked in at the Department of Pediatric Neurology. The initial diagnosis was "acute cerebellitis with ataxia" based on the elevated protein level in the cerebrospinal fluid (CSF). However, despite 3 months of treatment, her condition deteriorated. MRI showed an oval-shaped, intradural extramedullary nodule at the T6-T7 level. The patient was ultimately diagnosed as ALK-positive histiocytosis, accompanied by cauda equina and skin involvement. The literature review showed a total of 23 patients who had involvement of the nervous system and provided imaging descriptions. Together with our case, the imaging features were summarized as follows: iso-dense or slightly hyperdense on computed tomography (CT), isointense or iso-hypointense on T2-weighted imaging (T2WI), moderate homogeneous enhancement with mildly/markedly punctate enhancement or/and smooth ring enhancement on contrast-enhanced T1-weighted imaging (T1WI), restricted diffusion on diffuse weighted imaging (DWI), and elevated fluorodeoxyglucose (FDG) uptake on positron-emission tomography/computed tomography (PET/CT). The multimodal imaging findings of ALK-positive histiocytosis exhibit distinct characteristics, familiarity with which will enhance radiologists' expertise and facilitate accurate diagnosis of this disease.

Histiocytic neoplasms: a brief review and differential diagnosis.

Histiocytic neoplasms (HNs) include juvenile xanthogranuloma, Erdheim-Chester disease, Rosai-Dorfman disease, ALK-positive histiocytosis, and histiocytic sarcoma in the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours. These entities are clinicopathologically distinctive, and typical histological findings have been established. However, the common feature of a proliferation of histiocytic cells often leads to morphological overlap among HNs, and also necessitates a differential diagnosis from several non-HNs or non-neoplastic conditions. In this review, we provide a brief summary of the clinical findings, molecular features, histopathologies, and immunophenotypes of HNs, as well as to discuss their differential diagnosis.

Case report: ALK-positive histiocytosis presented as bilateral synchronous breast masses with long-term remission on crizotinib

ALK-positive histiocytosis (APH) is a rare type of histiocytic neoplasm with characteristic ALK (Anaplastic Lymphoma Kinase) gene translocation and fusion, with only 27 reported cases in the literature. In this study, we report the first case of synchronous bilateral breast involvement of ALK-positive histiocytosis on initial presentation in a 46-year-old Hispanic woman. APH was diagnosed by the confirmation of clonal histiocyte proliferation with ALK overexpression on IHC and the presence of KIF5B-ALK gene fusion from her breast and lung biopsies. The patient in our study is currently under complete and long-term remission with crizotinib treatment (an ALK inhibitor). This report expands on the clinical manifestation of APH, emphasizes the importance of ALK detection in histiocytic diseases, and provides the efficacy and long-term prognosis of the ALK inhibitor therapy for APH.

Malakoplakia with aberrant ALK expression by immunohistochemistry: a case report

BackgroundMalakoplakia is a rare inflammatory disease of the urogenital tract. There have been no reports of malakoplakia expressing anaplastic lymphoma kinase (ALK) to date. Here, we present one case of malakoplakia with aberrant ALK expression by immunohistochemistry and discuss the clinical significance.Case presentationA 65-year-old Chinese woman with a history of diabetes presented with solid masses in the liver and kidney and elevated lesions on the mucosal surface of the colon. Right nephrectomy and partial liver resection were performed. Microscopically, sheets of histiocytes with poor intercellular adhesion were seen, with Michaelis–Gutmann bodies present in both the intracellular and extracellular interstitium. CD10-, CD68-, and CD163-positive cells were present, with Michaelis–Gutmann bodies confirmed by staining with Alcian blue, periodic acid-Schiff (PAS), periodic acid-Schiff with diastase, Von Kossa, and Prussian blue. Aberrant ALK1 and ALK (D5F3) expression was observed in the cytoplasm and nucleus of cells. However, ALK gene mutation was not detected by fluorescence in situ hybridization or whole exome next-generation sequencing. NGS revealed nine individual somatic gene mutations: GOT1L1, GLIS2, SPOUT1, TMEM97, MUC3A, NSD2, SFXN5, ADAD1 and RAD50. The significance of the somatic gene mutations detected in this study is not clear, and the relationship between them and malakoplakia cannot be clarified by existing scientific studies. The pathological diagnosis was malakoplakia with aberrant ALK expression by immunohistochemistry. The antibiotics imipenem and vancomycin were started based on the results of drug sensitivity analysis and the patient was subsequently discharged. She experienced no discomfort during 30 months of follow-up.ConclusionThis is the first reported case of malakoplakia with aberrant ALK expression, it should be differentiated from ALK-positive histiocytosis to avoid misdiagnosis.

PU.1 is a useful nuclear marker to distinguish between histiocytosis and histiocyte-rich tumours.

The aim was to test the expression of PU.1 on different types of histiocytoses and to test the utility of PU.1 in confirming or excluding a histiocytic origin in tumour samples with suspicion of histiocytosis. We analysed 66 biopsies of nonmalignant histiocytoses represented by Langerhans-cell histiocytosis (n = 13), Erdheim-Chester disease (ECD) (n = 19), Rosai-Dorfman disease (RDD) (n = 14), mixed ECD-RDD (n = 3), ALK-positive histiocytosis (n = 6), and juvenile xanthogranuloma (n = 11). All cases were positive for PU.1 in reactive and neoplastic histiocytes. In addition, 39 cases of tumours with high-grade cytological atypia were referred to our center as suspicion of malignant histiocytosis/histiocytic sarcoma and only 18 were confirmed. Indeed, more than half of these tumours (21/39) were either undifferentiated malignant tumours with a stroma rich in histiocytes, diffuse large B-cell lymphoma, or high-grade dedifferentiated liposarcoma. PU.1 was useful to distinguish between the negativity of large atypical nuclei and the positivity of stromal reactive histiocytes. PU.1 is expressed by all types of histiocytosis. It distinguishes histiocytosis from histiocyte-rich tumours with an easy interpretation due to its sharp nuclear staining. Its negativity in lesional/tumour cells in histiocyte-like lesions is useful to eliminate a histiocytosis.

Epithelioid inflammatory myofibroblastic sarcoma: a pitfall in the differential diagnosis of ALK-positive anaplastic large cell lymphoma.

An 18-year-old female presented with a 4.5 cm abdominal mass. Biopsy showed sheet-like growth of large tumor cells with round to oval nuclei, 1-2 nucleoli, and abundant cytoplasm. Immunohistochemistry showed strong, uniform CD30 staining and cytoplasmic ALK staining. B-cell markers (CD20, CD79a, PAX5, kappa/lambda) and T-cell markers (CD2, CD3, CD4, CD5, CD43, granzyme B, T-cell receptor-β) were negative. Other hematopoietic markers (CD45, CD34, CD117, CD56, CD163, EBV) were negative, but CD138 was positive. Non-hematopoietic markers showed desmin positivity and negativity for S100, melan A, HBM45, PAX8, PAX2, WT1, MYO-D1, myogenin, pancytokeratin, and CAM5.2. Sequencing identified PRRC2B::ALK fusion. A diagnosis of epithelioid inflammatory myofibroblastic sarcoma (EIMS) was made. EIMS is a rare, aggressive form of inflammatory myofibroblastic tumor typically presenting in children and young adults. The tumor comprises large epithelioid cells that express ALK and often CD30. ALK-positive ALCL has a similar age range and also is a large-cell tumor expressing CD30 and ALK. Other ALK-positive neoplasms (e.g., carcinomas, ALK-positive large B-cell lymphoma, ALK-positive histiocytosis) typically lack CD30 and have distinct clinicopathologic features that aid diagnosis. Hematopathologists need to distinguish EIMS from ALK-positive ALCL, which frequently shows loss of pan-T-cell antigens. Careful morphologic evaluation for the hallmark cells of ALCL and comprehensive phenotyping are critical to avoid this diagnostic pitfall. If known, the ALK rearrangement partner gene may also provide diagnostic clues; for example PRRC2B::ALK and RANBP2::ALK occur in EIMS but not ALCL.

Multisystem ALK-positive histiocytosis: a multi-case study and literature review

BackgroundAnaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated.ResultsHere, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients’, whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed. Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case.ConclusionsWe observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease.

ALK-positive histiocytosis presenting as a solitary pulmonary nodule.

ALK-positive histiocytosis presenting as a solitary pulmonary nodule.

A case of ALK-positive histiocytosis with multiple lesions in the unilateral breast: A case report.

Introduction and importancePrimary ALK-positive histiocytosis of the breast is rare. Here, we report a case of ALK-positive histiocytosis with multiple unilateral breast lesions.Case presentationOur patient was a 38-year-old female with primary ALK-positive histiocytosis of the breast with multiple lesions. There were no lesions in other organs, and the patient was considered surgically resectable and underwent a left total mastectomy and sentinel lymph node biopsy. Histopathologically, there were at least three lesions in the left breast in upper inner quadrant (UIQ), upper quadrant (UQ), and upper outer quadrant (UOQ). All lesions showed spindle-shaped tumor cells that were positive for CD163 and ALK and negative for AE1/AE3. Fluorescence in situ hybridization (FISH) showed ALK and KIF5B rearrangements, suggesting the presence of the KIF5B-ALK fusion gene. In conclusion, this case was confirmed to be ALK-positive histiocytosis with multiple lesions in the unilateral breast. The patient underwent surgery and was discharged without complications.Clinical discussionReports of ALK-positive histiocytosis are very rare, and reports of primary cases in the breast are even rarer. The basic treatment for ALK-positive histiocytosis is surgical resection; however, ALK inhibitors may be effective in unresectable or disseminated cases. Accurate diagnosis at the time of initial treatment is necessary to expand the treatment options.ConclusionThis is the first case of ALK-positive histiocytosis with multiple lesions in the unilateral breast.

Failure of crizotinib based systemic treatment in ALK positive histiocytosis involving the central nervous system: a case report and literature review

BackgroundAmong the histiocytic disorders, anaplastic lymphoma kinase (ALK)-positive histiocytosis emerged in 2008. As more and more cases of the novel entity are reported, our understanding of it is deepened. However, only a few cases with central nervous system (CNS) involvement have been reported. Furthermore, the lesion in the suprasellar region has not been documented. Case presentationWe presented a case of ALK-positive histiocytosis involving the suprasellar region of a one-year-and-four-month-old boy. Through clinical, neuropathological, and genomic analyses, the patient was diagnosed with ALK-positive histiocytosis. After lesions were resected he started treatment with a combination of the three compounds vincristine, prednisolone, and crizotinib, but they did not work. Cytarabine was then added as an additional chemotherapy drug for him, and the lesions in the brain and lungs were shrunk by combining treatment of crizotinib, dexamethasone, vincristine, and cytarabine according to the RECIST (esponse Evaluation Criteria In Solid Tumours).ConclusionsAdditional adjuvant chemotherapy drugs are needed when ALK-inhibitor treatment is ineffective.