ABSTRACT
Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma (NHL) with poor prognosis, particularly in relapsed or refractory patients. Thus, timely detection of relapse and appropriate disease management are crucial. We present two patients with ENKTL, wherein positron emission tomography-computed tomography (PET-CT) with total-body coverage after induction therapy, detected newly relapsed regions in the bone marrow of the lower leg prior to progression. Case 1: A 47-year-old woman with nasal obstruction, showing 18F-fluoro-deoxyglucose (FDG) uptake in the nasal cavity (Lugano stage IE). After induction therapy (RT-2/3 DeVIC), PET-CT revealed abnormal uptake only in the right fibula. Case 2: A 68-year-old man with a skin nodule/ulcer and an enlarged right inguinal lymph node was diagnosed with advanced ENKTL. A PET-CT scan revealed abnormal uptake in the subcutaneous mass of the right medial thigh, lymph nodes, and descending colon (Lugano stage IV). After induction therapy, PET-CT revealed new abnormal uptake only in the left tibia. In both patients, CT-guided biopsy confirmed ENKTL recurrence. Moreover, PET-CT with whole-body coverage was useful for the timely assessment of relapse and detection of asymptomatic bone involvement. This approach allowed for modifications to treatment strategies in certain patients.
Subject(s)
Lymphoma, Extranodal NK-T-Cell , Positron Emission Tomography Computed Tomography , Male , Female , Humans , Middle Aged , Aged , Positron Emission Tomography Computed Tomography/methods , Bone Marrow/pathology , Positron-Emission Tomography/methods , Leg/pathology , Lymphoma, Extranodal NK-T-Cell/pathology , Fluorodeoxyglucose F18 , Radiopharmaceuticals , Neoplasm Recurrence, LocalABSTRACT
A 65-year-old woman was referred to the hospital for further investigation of weight loss, hyperproteinemia, and anemia. Serum immunofixation electrophoresis revealed IgM-κ M protein. Bone marrow examination revealed an increase in the number of B -cells with immunoglobulin kappa light-chain restriction. Although the MYD88 L265P mutation was identified in bone marrow mononuclear cells, which suggested the diagnosis of Waldenstrom's macroglobulinemia (WM), a fusion signal of IgH-MALT1, which is commonly observed in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, was also identified. Here, we describe a rare case of low-grade B-cell lymphoma with MYD88 L265P mutations accompanying IgH-MALT1.
ABSTRACT
Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described sinonasal tract tumor that is associated with high-risk HPV subtype infection. Despite histological features that are suggestive of a high-grade malignant tumor, the prognosis of HMSC is relatively good; however, the clinical features of this tumor are poorly understood. Here, we describe two patients with HMSC. The first was initially diagnosed with adenoid cystic carcinoma of the right nasal cavity; the tumor was extirpated via endoscopic endonasal surgery. Seventy-four months later, the tumor recurred in the right inferior turbinate and was diagnosed as HMSC after biopsy, whereupon it was resected en block via endoscopic endonasal surgery. No adjuvant therapy was administered during either episode; moreover, no recurrences have occurred during the 44 months since the second operation. The second patient was diagnosed with HMSC based on the biopsy of the tumor occupying the left nasal cavity. The tumor was completely resected under endoscopic endonasal surgery, and no adjuvant therapy was administered. There has been no recurrence for 15 months after the operation. Herein, we also review the clinical features of this tumor type based on 69 previously reported cases as well as our patients.
Subject(s)
Carcinoma, Adenoid Cystic , Carcinoma , Papillomavirus Infections , Paranasal Sinus Neoplasms , Humans , Human Papillomavirus Viruses , Paranasal Sinus Neoplasms/diagnostic imaging , Paranasal Sinus Neoplasms/surgery , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Carcinoma/pathology , Carcinoma, Adenoid Cystic/diagnostic imaging , Carcinoma, Adenoid Cystic/surgery , Turbinates/pathologyABSTRACT
Inclusion body myositis (IBM) is a refractory muscle disease characterized by inflammatory and degenerative features in myofibers. Macroglossia is common in systemic amyloid light chain amyloidosis; however, no reports have been published on patients with IBM. We encountered a female patient with clinicopathologically defined IBM who exhibited relatively rapid progression of dysphagia, gait disturbance, and macroglossia. Muscle biopsy demonstrated endomysial mononuclear inflammatory infiltrates, fiber necrosis and regeneration with rimmed vacuoles, and sarcoplasmic inclusions of p62. Tongue biopsy demonstrated fiber degeneration with fatty replacement and fibrosis, nonnecrotic fibers surrounded and invaded by mononuclear cells, and sarcoplasmic dotlike inclusions of p62. Based on the parotid gland, lip, and muscle biopsy, she was diagnosed as having IBM with Sjögren's syndrome. She was treated with steroid pulse and intravenous immunoglobulin therapy followed by oral administration of prednisolone, which resulted in temporary clinical improvement. Macroglossia might be an indicator of immunotherapy effectiveness.
Subject(s)
Macroglossia , Myositis, Inclusion Body , Humans , Female , Myositis, Inclusion Body/complications , Myositis, Inclusion Body/diagnosis , Myositis, Inclusion Body/pathology , Myocardium/pathologyABSTRACT
Follicular T-cell lymphoma (FTCL) is a rare disease, recently defined in the revised WHO classification Tumours of Haematopoietic and lymphoid tissues (4th edition). Although angioimmunoblastic T-cell lymphoma (AITL) and FTCL share similar T follicular helper (TFH) cell immunophenotypes and gene mutations, the clinical course of FTCL is not well characterized. Herein, we report the case of a 91-year-old woman with FTCL, who was successfully treated with corticosteroid. The patient, who had systemic lymphadenopathy and splenomegaly, was first diagnosed with necrotizing lymphadenitis. Re-biopsy was performed because of her persistent lymphadenopathy, which revealed FTCL. She was treated with corticosteroid because of her advanced age, poor performance, edema, and pleural effusion. After administering 100 mg prednisone, her condition improved and was discharged with prednisone tapering. Six-month positron emission tomography-computed tomography (PET-CT) scan showed complete metabolic remission. With a low dose of prednisone (6-10 mg), she remained disease-free for >3 years. Thus, these findings suggest that corticosteroid treatment is effective in some patients with peripheral T-cell lymphoma of TFH origin, including FTCL.
Subject(s)
Lymphoma, T-Cell, Peripheral , Humans , Aged, 80 and over , Lymphoma, T-Cell, Peripheral/drug therapy , Positron Emission Tomography Computed TomographyABSTRACT
AIMS: Dedifferentiation is a histological phenomenon characterised by abrupt transition of histology to a sarcomatous component with high-grade malignant potential in solitary fibrous tumour (SFT). The authors histologically reviewed SFT cases to reveal the histological background of dedifferentiated SFTs. METHODS: Clinicopathological and histopathological findings of 145 SFT cases were reviewed. Immunohistochemical staining and genetic analysis were also performed. RESULTS: The non-dedifferentiated components showed a cellular component in 45 of 145 (31%), high mitotic rate (≥4/10 high-powered field) in 12 of 145 (8.2%) tumours, necrosis in 7 of 145 (4.8%) tumours, multinodular growth pattern in 39 of 132 (29.5%) available tumours and intratumoural fibrous septa in 37 of 131 (28.2%). Immunohistochemically, the non-dedifferentiated components were positive for CD34 in 128 of 141 (90.7%), bcl-2 in 101 of 133 (75.9%), nuclear pattern of ß-catenin in 64 of 127 (50.3%) and p16 in 22 of 140 (15.7%). Loss of Rb protein expression was detected in 17 of 110 (15.4%) cases. Statistically, cellular component, multinodular structure, p16 overexpression and Rb protein loss were significantly associated with dedifferentiation. Moreover, cellular component and multinodular structure were significantly associated with p16 overexpression and Rb protein loss. All the non-deddifferentiated components showed wild type of p53 expression. The dedifferentiated components of all 10 dedifferentiated tumours presented positivity for p16 in 9 of 10 (90%) and mutational type of p53 in 5 of 10 (50%). Loss of Rb protein expression was detected in 6 of 10 (60%). CONCLUSIONS: The authors propose that cellular or multinodular transformation may be associated with dedifferentiation. They also suggest that cellular and multinodular transformation may be associated with p16 overexpression and Rb downregulation.
Subject(s)
Solitary Fibrous Tumors , Antigens, CD34/metabolism , Biomarkers, Tumor/analysis , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Humans , Retinoblastoma Protein/metabolism , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/pathology , Tumor Suppressor Protein p53/metabolismABSTRACT
INTRODUCTION: Definitive diagnosis of translocation renal cell carcinoma is challenging. We herein experienced a case of translocation(6;11) renal cell carcinoma, successfully diagnosed by using fluorescence in situ hybridization. CASE PRESENTATION: During the follow-up of a 21-year-old man with Crohn's disease, computed tomography revealed a 40-mm mass in the right kidney. Since imaging could not exclude malignancy, needle biopsy was performed. The histological diagnosis from the biopsy specimen was renal cell carcinoma, but histological typing had not been done adequately. A laparoscopic partial nephrectomy was then performed. Transcription factor EB immunoreactivity was positive, transcription factor EB rearrangement was shown by break apart and fusion fluorescence in situ hybridization. As a result, a definitive diagnosis of t(6; 11) renal cell carcinoma was made. There has been no recurrence for 5 years. CONCLUSION: Transcription factor EB immunohistochemistry and fluorescence in situ hybridization are useful diagnostic tools for renal tumors of young generation.
ABSTRACT
Sialadenoma papilliferum (SP) is a rare benign tumor of the salivary glands, and only 3 unequivocal cases of SP arising in the bronchus have been reported. We herein describe the histomorphologic and molecular features of 4 bronchial SP cases and discuss the differential diagnosis of this entity and the relationship with its clinicopathologic mimics, in particular, glandular papilloma and mixed squamous cell and glandular papilloma (GP/MP). We encountered 2 male and 2 female patients with bronchial SP (mean: 66.8 y old). All 4 tumors arose in the central bronchus and were characterized by a combination of surface exophytic endobronchial papillary proliferation and a submucosal multicystic component with complex architecture. The neoplastic epithelium consisted predominantly of nonciliated stratified columnar cells with ciliated, squamous, and mucinous cells present focally. While 2 tumors (50%) harbored a BRAF V600E mutation by molecular and immunohistochemical analysis, similar to GP/MP, no KRAS, HRAS, AKT1, or PIK3CA mutations were detected in any of the cases. Two patients were treated with limited resection, while 2 patients underwent lobectomy based on the diagnosis of adenocarcinoma or possible squamous cell carcinoma in situ in the preoperative biopsy. All survived without recurrence or metastasis for 23 to 122 months after treatment. SP can develop in the central bronchus as the bronchial counterpart of the salivary gland tumor and should be considered in the differential diagnosis of endobronchial tumors. In addition, some histologic resemblance and frequent BRAF V600E mutation raise the possibility of SP and GP/MP being on the same disease spectrum.
Subject(s)
Adenoma/genetics , Biomarkers, Tumor/genetics , Bronchial Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Salivary Gland Neoplasms/genetics , Adenoma/enzymology , Adenoma/pathology , Adenoma/surgery , Aged , Biomarkers, Tumor/analysis , Biopsy , Bronchial Neoplasms/enzymology , Bronchial Neoplasms/pathology , Bronchial Neoplasms/surgery , DNA Mutational Analysis , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Male , Middle Aged , Predictive Value of Tests , Salivary Gland Neoplasms/enzymology , Salivary Gland Neoplasms/pathology , Treatment OutcomeSubject(s)
Paget Disease, Extramammary , Palate, Hard/pathology , Aged, 80 and over , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/pathology , Diagnosis, Differential , Female , Humans , Mouth/pathology , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Neoplasm Grading , Neoplasm Recurrence, Local , Paget Disease, Extramammary/diagnosis , Paget Disease, Extramammary/pathology , PrognosisABSTRACT
Surgery with or without post-operative radiotherapy is the mainstay treatment for salivary gland carcinoma (SGC); however, palliative radiotherapy or supportive observation is considered for elderly patients. An 87-year-old female who was diagnosed with SGC in the left parotid gland, with a clinical stage T4aN2bM0 Stage IVA, underwent the Radiation Therapy Oncology Group 8502 "QUAD shot" regimen (14.8 Gy/4 fractions, twice-daily treatment with a 6 h interval, on 2 consecutive days), which were repeated every 4 weeks 3 times using volumetric modulated arc therapy. During and after the treatment, she experienced no acute toxicity but had Grade 1 xerostomia. At 4 months after completion of the treatment, [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/CT revealed a complete metabolic response to the treatment. She is still alive without any evidence of recurrence 9 months after completion of the treatment. The Radiation Therapy Oncology Group 8502 "QUAD shot" regimen using VMAT may be an effective palliative treatment for SGC with minimal toxicity.
ABSTRACT
We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37-year-old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2-weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill-defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct-like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S-100 protein, and p63, while are completely negative for p40, alpha-SMA, and calponin. The MEF2C-SS18 fusion was identified by reverse transcriptase-polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C-SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post-operative course was uneventful and there was no evidence of disease at 4 months after surgery.
Subject(s)
Actins/genetics , Adenocarcinoma/diagnostic imaging , Biomarkers, Tumor/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Salivary Gland Neoplasms/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Female , Gene Fusion , Humans , MEF2 Transcription Factors/genetics , Magnetic Resonance Imaging , Palate, Hard/diagnostic imaging , Palate, Hard/pathology , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/surgery , Salivary Glands, Minor/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Langerhans cell histiocytosis (LCH) is an abnormal accumulation of Langerhans cells in various organs that sometimes induces organ dysfunction. LCH can affect the liver, resulting in sclerosing cholangitis and biliary cirrhosis. However, liver and bile duct involvement is usually observed in the disseminated form of LCH. We herein report a rare case of LCH localized only in the extrahepatic bile duct that resulted in severe liver cirrhosis. CASE PRESENTATION: A 3-year-old boy with elevated liver enzymes, obstructive jaundice, and dilation of the common bile duct was referred to our institution. Contrast-enhanced computed tomography showed atrophy of the right hepatic lobe, relative hypertrophy of the left hepatic lobe, choledocholiths, and biliary debris extensively with biliary duct dilation. Magnetic resonance cholangiopancreatography revealed dilation of the intrahepatic and extrahepatic bile ducts and multiple choleliths in the gallbladder and common bile duct. Laparoscopic cholecystectomy, intraoperative cholangiography, liver biopsy, and gastrointestinal fiberscopy were performed. A liver specimen showed severe biliary cirrhosis due to sclerosing cholangitis. The patient then underwent living-donor liver transplantation because of severe liver cirrhosis 3 months after the first surgery. The common bile duct was not suitable for duct-to-duct anastomosis and was resected because of severe inflammation. Histologic sections of the common bile duct showed histiocytic cell proliferation. Immunohistochemistry revealed histiocytoses that were positive for Langerin, S-100 protein, and CD1a. However, no histiocytic cell proliferation was noted in the liver tissue. The definitive diagnosis was LCH localized to the extrahepatic bile duct. LCH in the extrahepatic bile duct seemed to cause sclerosing cholangitis. The patient was discharged uneventfully 2 months after living-donor liver transplantation. CONCLUSIONS: LCH localized to the extrahepatic bile duct is extremely rare; however, LCH can still affect the extrahepatic bile ducts on occasion. LCH should be considered as a differential diagnosis if pediatric patients show the presence of sclerosing cholangitis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Melanoma/drug therapy , Pancreatic Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Asymptomatic Diseases/therapy , Biopsy, Fine-Needle , Female , Humans , Imidazoles/pharmacology , Imidazoles/therapeutic use , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Melanoma/diagnosis , Melanoma/secondary , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Oximes/pharmacology , Oximes/therapeutic use , Pancreas/diagnostic imaging , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Pyridones/pharmacology , Pyridones/therapeutic use , Pyrimidinones/pharmacology , Pyrimidinones/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome , UltrasonographyABSTRACT
AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.
Subject(s)
Cystadenocarcinoma/genetics , Cystadenoma/genetics , Papilloma, Intraductal/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-akt/genetics , Salivary Gland Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Substitution , Cystadenocarcinoma/classification , Cystadenocarcinoma/diagnosis , Cystadenocarcinoma/pathology , Cystadenoma/classification , Cystadenoma/diagnosis , Cystadenoma/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Papilloma, Intraductal/classification , Papilloma, Intraductal/diagnosis , Papilloma, Intraductal/pathology , Salivary Gland Neoplasms/classification , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/pathology , Salivary Glands, Minor/pathologySubject(s)
Condylomata Acuminata/therapy , Electrocoagulation , Human papillomavirus 6/isolation & purification , Skin Neoplasms/therapy , Adult , Antineoplastic Agents/administration & dosage , Combined Modality Therapy , Condylomata Acuminata/pathology , Condylomata Acuminata/virology , Cryotherapy , Humans , Imiquimod/administration & dosage , Male , Perineum/pathology , Remission, Spontaneous , Skin/pathology , Skin Cream/administration & dosage , Skin Neoplasms/pathology , Skin Neoplasms/virology , Treatment OutcomeABSTRACT
Solitary fibrous tumor (SFT) is a soft-tissue neoplasm of intermediate malignant potential, presenting a wide histopathological spectrum. Poorer prognosis of hemangiopericytoma of the central nervous system (CNS), hypoglycemic SFT, and dedifferentiation are well-known characters of SFT, but their clinical significance were not demonstrated enough by large-sized study. Here, the clinicopathological features of SFTs are reviewed and the relationship between genetics and clinicopathological features is examined using 145 SFT cases. All cases were STAT6 IHC-positive and/or NAB2-STAT6 fusion gene-positive. Tumor location was classified into three categories: 30 pleuropulmonary, 96 non-pleuropulmonary/non-central nervous system (CNS), and 18 CNS tumors. The tumor developed recurrence in 21 of 93 available cases (22.5%), metastasis in 11 of 93 (11.8%), and tumor death in 9 of 93 (9.6%). Hypoglycemia occurred in 2 primary tumors and 1 metastatic tumor among 63 reviewable cases, and dedifferentiation occurred in 10 cases (6.8%) including 6 primary tumors, 2 recurrent tumors, and 2 metastatic tumors. Recurrence was positively associated with CNS location (p = 0.0109) and hypoglycemia (p = 0.001); metastasis was positively associated with CNS location (p = 0.0231), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001), while metastasis was negatively correlated with pleural location (p = 0.0471). Tumor death was positively associated with male sex (p = 0.0154), larger size (p = 0.0455), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001). Multivariate analysis revealed independent statistical significance of dedifferentiation for overall survival (p = 0.0467). Exon variant of the fusion gene had no statistical correlation with clinical outcome. In conclusion, dedifferentiation is a major prognostic factor of SFT, and specific location such as cerebromeningeal and intra-abdominal site and hypoglycemia also had a high risk for unfavorable prognosis.
Subject(s)
Solitary Fibrous Tumors/mortality , Solitary Fibrous Tumors/pathology , Adolescent , Adult , Aged , Cell Dedifferentiation , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young AdultSubject(s)
Myoepithelioma/surgery , Neoplasm Recurrence, Local/prevention & control , Skin Neoplasms/surgery , Aged , Biomarkers, Tumor/analysis , Biopsy , Forearm , Humans , Magnetic Resonance Imaging , Male , Myoepithelioma/diagnosis , Myoepithelioma/pathology , Skin/diagnostic imaging , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Transplantation , Treatment OutcomeSubject(s)
Fibroma/diagnosis , Hyperpigmentation/diagnosis , Lipomatosis/diagnosis , Skin Neoplasms/diagnosis , Adult , Ankle , Female , Fibroma/pathology , Humans , Hyperpigmentation/pathology , Lipomatosis/pathology , Skin Neoplasms/pathology , Subcutaneous Tissue/diagnostic imaging , Subcutaneous Tissue/pathology , Tomography, X-Ray ComputedABSTRACT
AIMS: Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by 'smudgy/grungy' calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings. METHODS AND RESULTS: A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT-PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement. CONCLUSIONS: It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)-FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis.