Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.
Biomarkers, Tumor/genetics* ; Child ; Chordoma/genetics* ; Diagnosis, Differential ; Female ; Humans ; Male ; Prognosis ; Rhabdoid Tumor/diagnosis* ; SMARCB1 Protein/genetics* ; Skull Base

A 51-year-old woman presented with severe dizziness. The brain magnetic resonance image revealed a 5.5 cm multiloculated mass with a thick rim in the left temporal lobe. Cytological examination of frozen diagnosis of the mass showed hypercellular sheets of round and rhabdoid cells in a hemorrhagic background, and two mitotic figures were observed. Histologically, the excised dura-based mass consisted of predominantly round cells with small foci of rhabdoid tumor cells in a pseudoalveolar pattern in a hemorrhagic background, and the cells showed nuclear positivity for signal transducer and activator of transcription 6 as well as frequent mitosis. The mass was diagnosed as a grade 3 solitary fibrous tumor (SFT)/hemangiopericytoma (HPC). The cytological diagnosis of SFT/HPC is challenging because of the heterogeneous cytological findings, such as histological heterogeneity, and because there are no standardized cytological criteria for malignant SFT/HPC. Cytological findings, such as singly scattered small cells, hypercellularity, rare ropy collagen, and round and rhabdoid cells with pseudoalveolar pattern, may assist in the diagnosis of malignant SFT/HPC.
Brain ; Central Nervous System ; Collagen ; Diagnosis ; Dizziness ; Female ; Hemangiopericytoma ; Humans ; Middle Aged ; Mitosis ; Population Characteristics ; Rhabdoid Tumor ; Solitary Fibrous Tumors ; STAT6 Transcription Factor ; Temporal Lobe

PURPOSE: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. Due to its extreme rarity, most of the available data are based on retrospective case series. To add to the current knowledge of this disease, we reviewed the patients treated for extra-cranial MRT in our institute. MATERIALS AND METHODS: A retrospective medical record review was conducted on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children's Hospital between January 2003 and May 2013. RESULTS: Eleven patients (7 boys, 4 girls) were diagnosed with extra-cranial MRT at a median age of 9 months old. INI1 staining was important in the pathological confirmation. Six patients (55%) had renal MRT and five (45%) had soft tissue MRT. Five patients (45%) had metastases at diagnosis. All patients underwent chemotherapy, eight patients (73%) underwent surgery, six patients (55%) received therapeutic radiotherapy, and four patients (36%) underwent high dose chemotherapy with autologous stem cell rescue (HDCT/ASCR) with melphalan, etoposide, and carboplatin. Five patients (45%) died of disease following progression (n=3) or relapse (n=2), however, there was no treatment related mortality. The overall survival of the cohort was 53.0% and the event-free survival was 54.5% with a median follow-up duration of 17.8 months (range, 2.3 to 112.3 months). CONCLUSION: Extra-cranial MRT is still a highly aggressive tumor in young children. However, the improved survival of our cohort is promising and HDCT/ASCR with melphalan, etoposide, and carboplatin may be a promising treatment option.
Carboplatin ; Child* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Etoposide ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; Medical Records ; Melphalan ; Mortality ; Neoplasm Metastasis ; Radiotherapy ; Recurrence ; Retrospective Studies ; Rhabdoid Tumor* ; Seoul ; Soft Tissue Neoplasms ; Stem Cells

OBJECTIVETo discuss the clinicopathologic features of rhabdoid glioblastoma of the brain and its differential diagnoses.

METHODSA 10-year-old and a 45-year-old female both presented with gradually worsening headache, limbs twitch and blurred vision. MRI scan revealed a contrast enhancing tumor in the right temporal lobe and left cerebellum respectively. Both patients underwent tumor resection, followed by postoperative radiotherapy and chemotherapy.

RESULTSMicroscopic examination of both tumors showed rhabdoid tumor cells with an eccentric nuclei and eosinophilic cytoplasms. Both tumors had areas of classic glioblastoma with microvascular proliferation and necrosis. Immunohistochemical staining showed the rhabdoid tumor cells were positive for vimentin diffusely and GFAP, EMA, CK focally. Integrase interactor (INI-1) was expressed in most tumor cells, but IDH1 R132H was not detected in both tumors. Fluorescence in situ hybridization revealed 1p/19q co-deletion in one case. One patient was alive without tumor recurrence after 16 months follow-up, the other patient died of intraspinal tumor dissemination 9 months after surgery.

CONCLUSIONSRhabdoid glioblastoma is a rare glial cell tumor with specific rhabdoid tumor cells, a highly aggressive clinical course and poor prognosis. Combining histological features, a panel of selected immunostains including vimentin, GFAP, CK, EMA, SMA and INI-1 is helpful in making an accurate diagnosis for those diagnostically challenging cases with rhabdoid features in central nervous system.

Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; pathology ; Child ; Diagnosis, Differential ; Female ; Glioblastoma ; pathology ; Humans ; In Situ Hybridization, Fluorescence ; Magnetic Resonance Imaging ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local ; Rhabdoid Tumor ; pathology ; Temporal Lobe ; pathology

Chromosomal Proteins, Non-Histone ; metabolism ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Keratins ; metabolism ; Male ; Mucin-1 ; metabolism ; Phosphopyruvate Hydratase ; metabolism ; Rhabdoid Tumor ; metabolism ; pathology ; surgery ; Rhabdomyosarcoma ; metabolism ; pathology ; S100 Proteins ; metabolism ; SMARCB1 Protein ; Sarcoma ; metabolism ; pathology ; Sarcoma, Clear Cell ; metabolism ; pathology ; Skin Neoplasms ; metabolism ; pathology ; surgery ; Transcription Factors ; metabolism ; Vimentin ; metabolism

Actins ; metabolism ; Calcium-Binding Proteins ; metabolism ; Calmodulin-Binding Proteins ; metabolism ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hysterectomy ; Leiomyoma, Epithelioid ; metabolism ; pathology ; Leiomyomatosis ; metabolism ; pathology ; surgery ; Leiomyosarcoma ; pathology ; Microfilament Proteins ; metabolism ; Middle Aged ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Rhabdoid Tumor ; metabolism ; pathology ; surgery ; Sarcoma, Endometrial Stromal ; metabolism ; pathology ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Vascular Neoplasms ; metabolism ; pathology ; surgery ; Veins ; pathology ; Vimentin ; metabolism

Female ; Humans ; Kidney ; pathology ; Kidney Neoplasms ; diagnosis ; Rhabdoid Tumor ; diagnosis

We report a very rare case of sellar and suprasellar atypical teratoid rhabdoid tumor (ATRT) in a 42-year-old female patient. The tumor was removed subtotally with a transsphenoidal approach. Histopathologic study showed rhabdoid cells with prominent nucleoli and abundant cytoplasm. Immunohistochemistry for INI1 was completely negative in the tumor cells, consistent with ATRT. After surgery, she received radiotherapy including spinal irradiation with proton beam therapy and subsequent chemotherapy, with no evidence of recurrence for more than 2 years. Up to date, this is the 8th case of an adult-onset ATRT in the sellar or suprasellar region. Despite its rarity, ATRTs should be considered in the differential diagnosis of an unclear malignant sellar or suprasellar lesion in adult patients and the treatment strategies for adult ATRT patients could be differentiated from those of pediatric ATRT patients.
Adult ; Cytoplasm ; Diagnosis, Differential ; Drug Therapy ; Female ; Humans ; Immunohistochemistry ; Proton Therapy ; Radiotherapy ; Recurrence ; Rhabdoid Tumor*

Rhabdoid tumor of the kidney (RTK) is a rare malignancy in infancy. Central nervous system involvement in RTK is already known. However, solitary spinal metastasis in RTK has been hardly reported. The authors report a case of metastatic RTK to spine causing paraplegia in an 8-month-old girl. Since the patient was young, the diagnosis of spine metastasis was delayed until paraplegia was seen after radical nephrectomy. Thorough neurological examination should be performed for early diagnosis of spinal metastasis in young patients with RTK. If there are any abnormal signs in neurologic examination, magnetic resonance images of brain and spine are recommended.
Brain ; Central Nervous System ; Diagnosis ; Early Diagnosis ; Female ; Humans ; Infant* ; Kidney* ; Neoplasm Metastasis ; Nephrectomy ; Neurologic Examination ; Paraplegia ; Rhabdoid Tumor* ; Spine*

OBJECTIVETo study the clinicopathologic characteristics of extrarenal malignant rhabdoid tumor (E-MRT) with emphasis on diagnosis and differential diagnosis.

METHODSThe clinical and pathologic data of 8 E-MRT cases were reviewed. The outcome was analyzed.

RESULTSThere were four males and four females. The age at presentation ranged from 3 days to 8 years (mean, 2.6 years; median, 3 years). The tumors were located in the extremities (n = 1), head and neck (n = 2), trunk (n = 2), cervical cord (n = 1), liver (n = 1) and retroperitoneum (n = 1). Histologically, the tumors were composed of a diffuse proliferation of rounded or polygonal cells with eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies, arranged in sheets and nests. Cellular atypia was easily observed and mitotic activity was high. Necrotic and hemorrhagic areas were abundant. On immunohistochemistry, the tumor cells expressed vimentin and epithelial marker such as EMA, AE1/AE3, and CAM5.2. The absence of INI1 protein expression was a distinctive feature. Follow-up of all eight cases revealed five deaths in one year and the other three were disease-free at last follow-up of one month, three months and seven months.

CONCLUSIONSE-MRT is a rare and highly aggressive tumor of infancy and childhood. Recurrence and distant metastasis was common and the 5-year survival rate is low. Increased awareness of the clinocopathologic features and immunophenotypes of E-MRT is helpful for correct diagnosis and effective treatment.

Child ; Child, Preschool ; Diagnosis, Differential ; Extremities ; Female ; Head and Neck Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Infant ; Infant, Newborn ; Male ; Neoplasm Recurrence, Local ; Retroperitoneal Neoplasms ; metabolism ; pathology ; Rhabdoid Tumor ; metabolism ; pathology ; Treatment Outcome ; Vimentin ; metabolism