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Phosphaturic mesenchymal tumors (PMTs) are extremely rare mesenchymal tumors of soft tissue and bone that cause tumor-induced osteomalacia (TIO). Some of these tumors are completely asymptomatic and may grow undetected unless they become large enough to cause pain or discomfort. This type of tumor is crucial to diagnose in patients being treated for phosphate metabolism disorders and are a rare reason why patients seek medical help owing to pain. Here, we report the details of a patient with progressive bone pain caused by a PMT originating in the left femur., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Phosphaturic mesenchymal tumors are rare, usually benign neoplasms that occur in the soft tissue or bone and are the cause of nearly all cases of tumor-induced osteomalacia. Tumor-induced osteomalacia due to phosphaturic mesenchymal tumor is a challenging diagnosis to make-patients present with variable clinical and radiologic findings and the culprit neoplasm is often small and can occur anywhere head to toe. We present two cases of phosphaturic mesenchymal tumor in the scapular body and plantar foot. In both cases, the patient endured years of debilitating symptoms before a tissue diagnosis was eventually reached. Descriptions of clinical presentation, laboratory workup, surgical resection, and imaging characteristics, with a focus on CT, MRI, and functional imaging, are provided to assist with the diagnosis and management of this rare entity. A brief review of current literature and discussion of the differential diagnoses of phosphaturic mesenchymal tumor is also provided., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with eosinophilic cytoplasm and abundant myxoid extracellular matrix. Although the majority of cases harbor a pathognomonic t(9;22) translocation that fuses EWSR1 with the orphan nuclear receptor NR4A3, there are less common variants that partner NR4A3 with TAF15, TCF12, or TFG. By immunohistochemistry, EMC has features of both cartilaginous and neuroendocrine differentiation, as evidenced by inconsistent expression of S100 protein and synaptophysin or INSM1, respectively, in a subset of cases. Given the limitations of available immunohistochemical stains for the diagnosis of EMC, we analyzed genome-wide gene expression microarray data to identify candidate biomarkers based on differential expression in EMC in comparison with other mesenchymal neoplasms. This analysis pointed to CHRNA6 as the gene with the highest relative expression in EMC (96-fold; P = 8.2 × 10 -26 ) and the only gene with >50-fold increased expression in EMC compared with other tumors. Using RNA chromogenic in situ hybridization, we observed strong and diffuse expression of CHRNA6 in 25 cases of EMC, including both EWSR1-rearranged and TAF15-rearranged variants. All examined cases of histologic mimics were negative for CHRNA6 overexpression; however, limited CHRNA6 expression, not reaching a threshold of >5 puncta or 1 aggregate of chromogen in >25% of cells, was observed in 69 of 685 mimics (10.1%), spanning an array of mesenchymal tumors. Taken together, these findings suggest that, with careful interpretation and the use of appropriate thresholds, CHRNA6 RNA chromogenic in situ hybridization is a potentially useful ancillary histologic tool for the diagnosis of EMC., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary epithelioid hemangioendothelioma is a rare malignant disease, and most cases are found as multiple lung nodules, rarely as a single nodule., Case: Computed tomography( CT) in a 71-year-old man revealed a growing 3-mm lung nodule in the left S6 after rectal cancer operation. Wedge resection was performed. A pathological examination resulted in a diagnosis of pulmonary epithelioid hemangioendothelioma based on CD31 and CD34 positivity in immunohistochemistry., Conclusion: When new nodules are noted on routine CT scans of other malignancies, it is essencial to make a pathological diagnosis, bearing in mind that pulmonary nodules can arise from a variety of causes.

Phosphaturic mesenchymal tumor (PMT) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, and bone calcification disorders. Complete surgical resection of the tumor is believed to be the most effective treatment measure. However, the diagnosis of PMT is very difficult because of its insidious and small size, especially, when it appears in subcutaneous tissue with a chronic non-healing wound. We report a rare case of a 38-year-old man with a chronic non-healing wound on the left hallux for approximately eight months. Plain radiographic images and magnetic resonance imaging (MRI) revealed a cystic radiolucent shadow in the left distal phalanx. Bone scan observations also showed increased uptake in the same location. Histologically, this tumor was composed of numerous spindle cells with clusters of giant cells. The serum FGF23 level was significantly higher before surgery, with higher FGF23 levels closer to the tumor. Reverse transcription polymerase chain reaction and immunohistochemistry further confirmed the high expression of FGF23 in tumors. These data suggest that FGF23 may be a potential causative factor of PMT. The serum FGF23 levels might be useful for the diagnosis of PMT and localization of the tumor. The tumor was CD56- and D2 to 40-positive and CD31-negative. The non-healing wound caused by PMT might be attributed to the invasive growth of the tumor, destruction of intercellular junctions, and decrease in the number of endothelial cells., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia., Materials and Methods: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission., Results: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%., Conclusion: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

Objective: This study aimed to examine the differences in the fungal microbiome between patients with conjunctival mucosa-associated lymphoid tissue (MALT) and healthy controls using metagenomic analysis., Methods and Analysis: This case-control study was conducted at Osaka University Hospital in Osaka, Japan, from April 2015 to March 2022. Twenty-five consecutive patients with conjunctival MALT lymphoma and 25 healthy volunteers were included. Metagenomic analysis using Internal Transcribed Spacer (ITS)1 deep sequencing and hierarchical clustering was performed to investigate differences in the fungal microbiome. To assess tear environmental change, we measured tear mucin concentrations using ELISA., Results: Detailed analyses showed fungal dysbiosis and changes in β-diversity within the conjunctiva of patients with conjunctival MALT lymphoma. Hierarchical clustering revealed that the participants could be divided into three clusters according to the Malassezia abundance: cluster I ( Malassezia abundance above 70%), cluster II ( Malassezia abundance 25%-70%) and cluster II ( Malassezia abundance below 25%). Most patients were included in cluster I, whereas most of healthy controls were included in cluster III. The differences were significant. Tear mucin concentrations were significantly lower in patients with MALT compared with healthy controls., Conclusion: The metagenomic analysis using ITS1 deep sequencing was useful for identifying the differences in commensal fungi between patients with MALT lymphoma and healthy individuals. The increased prevalence of the Malassezia genus and the decreased levels of tear mucin can lead to an allergic response of the conjunctiva, resulting in the pathogenesis associated with conjunctival MALT lymphoma. Therefore, it may be beneficial to initiate treatment when a high abundance Malassezia is detected., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Squamoid eccrine ductal carcinoma (SEDC) is a poorly documented but likely underrecognized sweat gland malignancy with significant risk for local recurrence and potential for metastasis and rare disease-related mortality. Histopathologically, the tumor demonstrates a biphasic differentiation pattern: superficially, the tumor has squamous differentiation [indistinguishable from well-differentiated cutaneous squamous cell carcinoma (cSCC)], while the deeper aspect has a more infiltrative pattern with prominent ductal differentiation. Diagnosis of SEDC relies upon histopathologic examination alone. Its pathogenesis is poorly understood, and its genomic features have yet to be described. In this article, we characterize the genomic features in a case of SEDC through whole-exome sequencing, then compare its features with cSCC and other eccrine ductal carcinomas. Whole-exome sequencing revealed 30 mutations/Mb with 21 pathogenic or likely pathogenic mutations in total, identified across 14 different genes. The genomic abnormalities identified in this case of SEDC overlap considerably with those found in cSCC but not those of other sweat gland malignancies. The clinical and histopathologic features of SEDC previously reported and the genetic features determined from this case suggest that this tumor may arise initially as a well-differentiated cSCC that subsequently undergoes divergent differentiation focally to resemble a sweat gland malignancy. Genetic analyses of additional cases are warranted to clarify this consideration., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

External auditory canal cancer is a rare disease which can be treated by surgery or chemoradiation. The most common histological type is squamous cell carcinoma, but rare types such as adenocarcinoma have been reported and are thought to be derived from the ceruminous glands. Here, we present a case of ceruminous adenocarcinoma, not otherwise specified (NOS) in the external auditory canal. A 72-year-old woman was referred to our department with discomfort due to a mass in the external ear canal. No typical symptoms of malignancy, such as pain or bleeding, were noted at the initial examination. The patient underwent a total excision under local anesthesia as a diagnostic treatment. She was diagnosed with ceruminous adenocarcinoma, NOS based on the results of immunostaining of the excised specimen, and is currently being followed up as an outpatient. Adenocarcinoma is thought to originate from the cerumen glands of the ear canal and the lack of specific symptoms may make it difficult to differentiate it from benign tumors. Although adenocarcinoma, NOS has been reported in the head and neck region, there have been no reported cases occurring in the external ear canal, and to the best of our knowledge, this is the first report.

The experience with uterine inflammatory myofibroblastic neoplasms with an unfavorable outcome is limited. We present the clinicopathologic features of 9 such cases, including 8 inflammatory myofibroblastic tumors (IMTs) and 1 epithelioid inflammatory myofibroblastic sarcoma (EIMS). Median patient age for the IMT group was 50.5 years; the patient with EIMS was 43 years old. Patients presented with abnormal uterine bleeding, presumed fibroids, pelvic pain, arthralgia and low-grade fever, as well as an incidental finding. Median tumor size for the IMTs was 8.5 cm. The borders were either infiltrative or well-circumscribed. Histologically, IMTs were purely fascicular or myxoid or showed predominance of one or the other pattern. Seven tumors were spindled, and 1 was both spindled and epithelioid. Tumors had variable nuclear atypia, ranging from grade 1 to 3. All tumors had an inflammatory infiltrate-predominantly lymphocytic, majority had necrosis (62.5%) and none had lymphovascular invasion. 7/8 (87.5%) tumors were positive for ALK-1 by immunohistochemistry (IHC). One tumor was negative for ALK-1 by IHC but was positive for ALK fusion by fluorescence in situ hybridization and had TNS1-ALK fusion by next-generation sequencing (NGS). Three other tumors with NGS testing showed one of the following ALK-fusion partners: FN1, DCTN1, and IGFBP5. The EIMS had infiltrative borders, myxoid and hyalinized patterns, epithelioid cells, and no lymphovascular invasion. This tumor was ALK-1 positive by IHC, had ALK rearrangement by fluorescence in situ hybridization and RANBP2-ALK fusion by NGS. Extrauterine disease at time of diagnosis was noted in 2/8 (25%) of IMTs, and in the single case of EIMS. Seven patients had surgery as primary treatment, 1 patient had neoadjuvant chemotherapy and 1 patient declined treatment. Patients with recurrence were treated with a combination of chemotherapy, targeted therapy, radiotherapy or hormonal therapy. Most patients (71.4%) recurred within 24 months (mos). Two thirds of patients were alive with disease at last follow up (mean 43.6 mos). The patient with EIMS was alive with disease at 22 mos. IMT referral cases were initially diagnosed as smooth muscle tumors in 87.5% of cases; while the EIMS was diagnosed as high-grade endometrial stromal sarcoma. Lack of consideration of IMT in the differential diagnosis of smooth muscle tumors with myxoid features can result in misdiagnosis and under-utilization of targeted therapy in these patients., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Verrucous venous malformation (VVM), previously called "verrucous hemangioma," typically involves the dermis and the subcutaneous fat. We have encountered patients with VVM confined to the hypodermis., Materials and Methods: During a nearly 20-year period, 13 patients, aged 2-17 years, presented with a subcutaneous mass in the limb without clinically obvious epidermal alterations. Consequently, operative excisions did not include the skin., Results: Histopathologically, the specimens were composed of blood-filled channels with morphologic characteristics of capillaries and veins that infiltrated adipose tissue. Aggregates often formed nodules with variable fibrosis and a component of large and radially oriented vessels. A diagnosis of VVM was supported by endothelial immunopositivity for GLUT-1 (25%-75% immunopositive channels in 16/16 specimens); D2-40 (1%-25% channels in 14/15 specimens); and Prox-1 (1%-50% of channels in 14/16 specimens). A MAP3K3 mutation was identified by droplet digital PCR in 3 of the 6 specimens., Conclusions: Diagnosis of VVM in this uncommon location is challenging because of absence of epidermal changes and lack of dermal involvement. Imaging is not pathognomonic, and mimickers are many. Appropriate immunohistochemical stains and molecular analysis contribute to the correct diagnosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Mimickers of neuroendocrine neoplasms (NEN) include a number of important pitfall tumors. Here, we describe our experience with mesenchymal mimics of NENs to illustrate their spectrum and draw the attention particularly to a group of mesenchymal/non-epithelial neoplasms (MN) that combine epithelioid histology with neuroendocrine (NE-) features and peculiar genetic abnormalities. In a consultation series of 4498 cases collected between 2009 and 2021, 2099 neoplasms expressing synaptophysin and/or chromograninA were reviewed and analyzed. A total of 364 (18%) were diagnosed as non-NENs, while the remaining tumors were NEN. The group of mesenchymal/non-epithelial neoplasms with NE-features (MN-NE) included 31/364 (8%) cases. These mostly malignant neoplasms showed an epithelioid morphology. While all but one tumor expressed synaptophysin, mostly patchy, only 10/29 (34%) co-expressed chromograninA. A total of 13/31 (42%) of the MN-NE showed EWSR1-related gene fusions (6 Ewing sarcomas, 5 clear cell sarcomas, and 1 desmoplastic small round cell tumor, 1 neoplasm with FUS-CREM gene fusion) and 7 (23%) were SWI/SNF (SMARCB1 or SMARCA4)-deficient neoplasms. The remaining MN-NE included synovial sarcoma, sclerosing epithelioid mesenchymal neoplasm, melanoma, alveolar soft part sarcoma, solitary fibrous tumor, and chordoma. A total of 27/31 MN-NE were from the last 8 years, and 6 of them were located in the pancreas. Eleven MN-NE were initially diagnosed as neuroendocrine carcinomas (NECs). MN-NE with epithelioid features play an increasing role as mimickers of NECs. They mostly belong to tumors with gene fusions involving the EWSR1 gene, or with SWI/SNF complex deficiency. Synaptophysin expression is mostly patchy and chromograninA expression is infrequent in MN-NE of this series and data extracted from literature., (© 2021. The Author(s).)

The self-limited nature of nodular fasciitis (NF) is well-known but its precise mechanism has not yet been clarified. We observed that "young" NF (preoperative duration <1 month) consistently contains a higher percentage (~80%) of USP6 break-apart FISH signals than "old" NF (preoperative duration >3 months) (~20%). Thus, we hypothesized that our original observation may reflect a connection with the self-limited nature of NF. Seventeen cases with reliable data concerning the onset were selected, thus approximating the lifetime of each tumor. Besides the USP6 interphase FISH examination, we also checked the most common MYH9-USP6 fusion using RT-PCR. Because of the known pathways of the tumorigenesis of NF, the mRNA level of USP6, TRAIL, IFN-beta, JAK1, STAT1, STAT3, JUN, and CDKN2A was measured using qRT-PCR. Regarding proteins, USP6, p16, p27, TRAIL, and IFN-beta were examined using immunohistochemistry. Targeted gene panel next-generation sequencing (NGS) of three cases was additionally performed. We found a strong negative correlation (p = 0.000) between the lifetime and percentage of USP6 break-apart signals and a strong positive relationship (p = 0.000) between USP6 break-apart signals and mitotic counts. Results of immunostainings, along with qRT-PCR results, favored the previously-suggested USP6-induced negative feedback mechanism through activation of TRAIL and IFN-beta, likely resulting in apoptosis and senescence of tumor cells harboring USP6 fusions. Targeted-NGS resulted in the detection of several variants, but no additional recurrent changes in the pathogenesis of these tumors. We revealed on a cellular level the USP6-induced negative feedback mechanism. In conclusion, we emphasize that in "old" NF, the percentage of USP6 break-apart FISH signals can be as low as 14-27% which can be very important from a differential diagnostic point of view. We emphasize that a careful examination and interpretation of the NGS data is needed before clinical decision-making on treatment., (© 2021. The Author(s).)

Background: When assessing sharply delineated bone lesions of the mandibular angle on X-rays, numerous diagnoses must be considered. The static bone cavity (Stafne's bone cavity, SBC) is a harmless lingual bone depression of the mandibular angle that usually does not require any treatment. It is essential to differentiate this bone deformity from other lesions that may require treatment., Case Report: The 22-year-old patient was referred for further diagnosis and therapy after osteolysis of the mandible was noticed on a panoramic view (PV). The location and size of the lesion was typical of SBC. Only the three-dimensional representation of the lesion on cone beam computed tomographs revealed an intraosseous lesion. Histological examination of the lesion provided evidence of a fibrous neoplasm., Conclusion: The typical image of SBC is ambiguous on plain radiographs such as PV. The radiological diagnosis of the lesion should be based on the representation of the region of interest in different planes., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Translocations involving FN1 have been described in a variety of neoplasms that share the presence of a cartilage matrix and may also contain a variable extent of calcification. Fusions of FN1 to FGFR1 or FGFR2 have been reported in nine soft tissue chondromas, mostly demonstrated indirectly by FISH analysis. Delineation of FN1 fusions with various partner genes will facilitate our understanding of the pathogenesis and diagnostic classification of these neoplasms. In this study, we present molecular, clinical, and pathologic features of 12 cartilaginous soft tissue neoplasms showing a predilection for the TMJ region and the distal extremities. We analyzed for gene fusions with precise breakpoints using targeted RNA-seq with a 115-gene panel. We detected gene fusions in ten cases, including three novel fusions, FN1-MERTK, FN1-NTRK1, and FN1-TEK, each in one case, recurrent FN1-FGFR2 fusion in five cases, FN1-FGFR1 in one case, and FGFR1-PLAG1 in one case. The breakpoints in the 5' partner gene FN1 ranged from exons 11-48, retaining the domains of a signal peptide, FN1, FN2, and/or FN3, while the 3' partner genes retained the transmembrane domain, tyrosine kinase (TK) domains, and/or Ig domain. The tumors are generally characterized by nodular/lobular growth of polygonal to stellate cells within a chondroid matrix, often accompanied by various patterns of calcification, resembling those described for the chondroblastoma-like variant of soft tissue chondroma. Additional histologic findings include extensive calcium pyrophosphate dihydrate deposition in two cases and features resembling tenosynovial giant cell tumor (TGCT). Overall, while the tumors from our series show significant morphologic overlap with chondroblastoma-like soft tissue chondroma, we describe findings that expand the morphologic spectrum of these neoplasms and therefore refer to them as "calcified chondroid mesenchymal neoplasms." These neoplasms represent a spectrum of chondroid/cartilage matrix-forming tumors harboring FN1-receptor TK fusions that include those classified as soft tissue chondroma as well as chondroid TGCT.

Conjunctival stromal tumor (COST) is an emerging entity with only a limited number of cases reported in the literature. In this report, we describe 2 additional cases, review the accumulative clinical and histopathological features and expand on the immunophenotypic property of this entity. COST appears to have a sporadic presentation, affecting both sexes and patients of variable ethnicity and age group and predominantly occurring on the bulbar conjunctiva as a slow-growing asymptomatic or slightly tender mass-like lesion. Histopathologically, COST is characterized by singly dispersed spindle to round cells, often with some degree of degenerative nuclear atypia, within a myxomatous to collagenous stroma. Lesional cells are characteristically positive for CD34 and vimentin, negative for S100, SOX10 and STAT6 and show a normal pattern of staining with RB1 by immunohistochemistry. The reported cases to date have shown an indolent biological behavior, reliably treated by a complete surgical excision.

In this article, we describe a spindle cell neoplasm harboring an EML4-ALK gene fusion presenting as an intraosseous vertebral mass with extension into the adjacent soft tissue in a 65-year-old man. Histologically, the lesion was characterized by the presence of monotonous, cytologically bland spindle cells with loose myxoedematous stroma and interspersed areas of amianthoid-like collagen fiber deposition. Immunohistochemistry demonstrated strong diffuse staining for CD34 and S100, with absent immunoreactivity for SOX10. At 1 year of follow-up after resection, there is no evidence of local recurrence or metastatic disease. This case adds to the clinical and pathologic spectrum of the recently described group of kinase fusion-positive spindle cell neoplasms and represents the first reported intra-osseous example. The presence of ALK rearrangement in this lesion represents a potential therapeutic target, if clinically indicated., (© 2020 Wiley Periodicals LLC.)

Perianal Paget disease (PPD) is a rare neoplastic condition defined by the presence of atypical Paget cells in the perianal skin, the aetiology of which remains largely unknown. It can be divided in primary forms, arising as an intraepithelial disease or manifestation of an underlying skin adenocarcinoma or secondary forms resulting from epidermotropic spread or metastasis of a concealed carcinoma. Indeed, because of its rarity, clear options regarding the treatment of these patients are yet to be clarified. A high level of suspicion is needed whenever dealing with any unhealed perianal skin lesions and, therefore, the need for close long-term follow-up must be highlighted. Herein, two cases of PPD, one primary and another secondary, treated at the same institution, are presented in an attempt to document the involved complexity and to bring further insight into the understanding of this entity., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Periductal stromal tumors (PSTs) of the breast are considered as a rare subtype of phyllodes tumors. These rare fibroepithelial lesions display a biphasic morphology, characterized by a cellular stroma surrounding benign ducts. Unlike phyllodes tumors, they do not present with a leaflike architecture, rendering a biopsy diagnosis of a PST very challenging. In this report, we compare the histopathological features of a PST with those of a borderline phyllodes tumor. We discuss the differences and similarities between both entities, and we highlight the potential pitfalls of the respective biopsies. Both cases illustrate that PSTs and phyllodes tumors are part of the same spectrum. This biological spectrum implies that "hybrid" lesions do exist, which can be hard to classify.

Traditionally patient owners express their concerns that surgical or diagnostic procedures on a tumor may induce metastasis. In pets, this has been documented in only very rare occasions, e. g. needle path metastases after diagnostic fine needle biopsies of urinary bladder or prostatic tumors. Here, we describe a case of subcutaneous seeding of a feline intracranial grade 1 meningioma 6 months after surgical resection. A 10-year-old male neutered domestic shorthaired cat with typical neurological signs was diagnosed with an extra-axial contrast enhancing mass in the dorsal frontotemporal lobes using magnetic resonance imaging (MRI). Transfronto-parietal bone craniotomy was performed and the 24 × 19 × 22 mm large tumor was largely removed. Tumor recurrence after 12 months resulted in a second surgical tumor removal. In addition, 2 subcutaneous masses of 10 × 4 × 4 mm in size were removed at the site of the original surgical site which were fully separated from the recurring meningeal tumor by the intact frontal bone. Histology and immunohistochemistry suggested the same tumor growth in all 4 masses. Most likely the tumor seeding had been caused during the first surgery. After all, the risk of surgical seeding of a benign tumor seems very low., Competing Interests: The authors confirm that they do not have any conflict of interest., (Thieme. All rights reserved.)

We report a case of solitary infantile myofibroma (IM) with partially CD34-positive neoplastic cells on the back of a newborn boy. Ultrasonography showed a multilocular mass with a hypoechoic center surrounded by an isoechoic rim. Histopathological analysis revealed that the lesion was composed of small, round cells that were tightly packed and uniform. The cells had oval nuclei and were pale, CD34-positive, and richly cellular. They had interlacing fascicles of spindle cells with features of myofibroblasts with α-smooth muscle actin positivity. We speculate that neoplastic cells in most IMs differentiate towards myofibroblasts. However, in rare cases, their differentiation is more primitive and they express CD34, with or without α-smooth muscle actin expression.

Background: Fine-needle aspiration cytology (FNAC) being a fast technique is used as a primary investigation to diagnose wide spectrum of hand, wrist, and foot lesions. These sites are prone to trauma, reparative, and infectious process, which forms mass lesions mimicking neoplasia. Our study highlighted the importance of FNAC with the chance of reduction in biopsy or excision., Aims and Objectives: To report the prevalence and cytomorphological spectrum of hand and foot lesions with the aim of consolidating the diagnostic potential and also correlate the cytological evaluation with histopathology., Materials and Methods: This retrospective observational study was done in central India for the period of 5.5 years. The archive cytology slides of patients with palpable lesions at these sites are reviewed and analyzed., Results: Of the total 6512 FNAC cases, 115 cases presented as swelling in the hand, wrist, and foot are reviewed. Age ranged from 4 months to 80 years with M:F = 1.25:1. Of the 111 satisfactory smears (96.7%), 21 cases (18.9%) diagnosed as inflammatory lesion, including synovitis, tuberculosis, gout, and fat necrosis. Sixty cases as benign non-neoplastic (tumor-like) lesions with the most common being ganglion (29). Of the 30 neoplastic lesions, 26 were benign tumor with the most common being mesenchymal neoplasms (19), followed by giant cell tumor of tendon sheath. Malignant tumors included malignant melanoma, small round cell tumor, and squamous-cell carcinoma., Conclusion: FNAC is useful investigation for early diagnosis of hand and foot lesions. These lesions are benign mostly with less malignancy occurrence (<2%), compared with other soft tissue lesions., (© 2020 Wiley Periodicals LLC.)

We summarize herein the literature data about molecular targeted therapies in sarcomas and conjunctive tissue intermediate malignancies. For each clinical setting, the level of evidence, the mechanism of action and the target are described. The two major axes include (i) identification of subgroups of tumors with druggable alteration irrespective of the histological diagnosis (e.g. NTRK), and (ii) druggable target of pathway related to the physiopathology of the tumor: denosumab and bone giant cell tumor, imatinib and soft tissue giant cell tumor, mTOR inhibitor and PECOMA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Extracellular matrix (ECM) plays a central and dynamic role in the creation of tumor microenvironment. Herein we discuss the emerging biophysical and biochemical aspects of ECM buildup and proteolysis in cancer niche formation. Dysregulated ECM remodeling by cancer cells facilitate irreversible proteolysis and crosslinking, which in turn influence cell signaling, micro environmental cues, angiogenesis and tissue biomechanics. Further, we introduce the emerging roles of cancer microbiome in aberrant tumor ECM remodeling and membrane bound nano-sized vesicles called exosomes in creation of distant pre-metastatic niches. A detailed molecular and biophysical understanding of the ECM morphologies and its components such as key enzymes, structural and signaling molecules are critical in identifying the next generation of therapeutic and diagnostic targets in cancer., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The tumor microenvironment (TME) is a complex meshwork of extracellular matrix (ECM) macromolecules filled with a collection of cells including cancer-associated fibroblasts (CAFs), blood vessel associated smooth muscle cells, pericytes, endothelial cells, mesenchymal stem cells and a variety of immune cells. In tumors the homeostasis governing ECM synthesis and turnover is disturbed resulting in abnormal blood vessel formation and excessive fibrillar collagen accumulations of varying stiffness and organization. The disturbed ECM homeostasis opens up for new types of paracrine, cell-cell and cell-ECM interactions with large consequences for tumor growth, angiogenesis, metastasis, immune suppression and resistance to treatments. As a main producer of ECM and paracrine signals the CAF is a central cell type in these events. Whereas the paracrine signaling has been extensively studied in the context of tumor-stroma interactions, the nature of the numerous integrin-mediated cell-ECM interactions occurring in the TME remains understudied. In this review we will discuss and dissect the role of known and potential CAF interactions in the TME, during both tumorigenesis and chemoresistance-induced events, with a special focus on the "interaction landscape" in desmoplastic breast, lung and pancreatic cancers. As an example of the multifaceted mode of action of the stromal collagen receptor integrin α11β1, we will summarize our current understanding on the role of this CAF-expressed integrin in these three tumor types., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution., Study Design: Retrospective case series., Setting: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University., Subjects and Methods: We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019., Results: There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia., Conclusions: A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.

» Assessment of chondral lesions begins with a clinical evaluation and radiographs. » Longitudinal follow-up with serial radiographs is appropriate in cases without evidence of aggressive radiographic features. » Concerning radiographic features include periosteal reaction, soft-tissue extension, cortical destruction, endosteal scalloping of greater than two-thirds of the native cortex, larger lesion size (≥5 cm), and location in the axial skeleton. » Biomarkers such as IMP3, SOX4, microRNA, and periostin may be used as an adjunct in histologic assessment to help differentiate benign enchondroma from a low-grade chondrosarcoma. » Advanced-imaging studies, such as computed tomography (CT), bone scans, magnetic resonance imaging (MRI), dynamic contrast-enhanced MRI, and fluorodeoxyglucose positron emission tomography (FDG-PET), may be considered for borderline cases. » Aggressive or concerning radiographic features should prompt evaluation with advanced imaging or referral to an orthopaedic oncologist.

Marine mussel production is of substantial economic interest in numerous coastal areas worldwide, making crucial the study of pathologies that affect them. Disseminated neoplasia (DN) has recently been suggested to be linked to blue mussel, Mytilus edulis, mortality outbreaks observed in France since 2014, although the evidence remains indirect. In order to improve DN detection and monitoring, we compared the sensitivity of four diagnostic tools, namely haemocytology, histology, flow cytometry, and genetics. Haemocytological examination gave the best results in sensitivity and had the advantage of being non-invasive, allowing disease progression to be followed in affected mussels. Using this approach, we showed that DN progression is usually slow, and we provide evidence of remission events. We observed a high diversity of forms and mitotic features of neoplastic cells located in the vesicular connective tissue but rarely in the haemolymph. Circulating cells occur as four main types but are homogenous in morphology and DNA content within a single individual. Polyploidy proved very high, from 8 N to 18 N. Genetic analysis of haemolymph DNA showed that a Mytilus trossulus genetic signal was associated with almost all the DN cases here diagnosed by haemocytological examination, regardless of the DN type. This result corroborates DN is a transmissible cancer that first originated in a M. trossulus host and subsequently crossed into M. edulis. No pre-neoplastic conditions were detectable. The prevalence of the disease was quite low, which, together with the low morbidity observed in the lab, suggest DN is unlikely to be the direct cause of mortality outbreaks in France., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To investigate the differences of clinicopathological features, diagnosis, treatment and prognosis between patients with extra-gastrointestinal stromal tumors (EGIST) and duodenal gastrointestinal stromal tumors (DGIST). Methods: A retrospective case - control study was performed. Case inclusion criteria: (1) tumor confirmed by histology and pathology; (2) primary tumor locating in the extra - gastrointestinal tract or duodenum; (3) without other synchronous tumors; (4) complete clinical and pathological data. Clinical data of 20 EGIST patients and 32 DGIST patients from March 2011 to September 2016 at Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were retrospectively collected and analyzed. The observational parameters included clinicopathological characteristics, treatment and prognosis conditions. Continuous data of abnormal distribution were expressed as median (range) and compared using the Mann-Whitney U -test. Survival curves were drawn by the Kaplan-Meier method and compared with the Log-rank test. Results: Of the 20 EGIST patients, 8 were males and 12 were females with age of 61.0 (30.0 to 86.0) years and of the 32 DGIST patients, 12 were males and 20 were females with age of 55.5 (27.0 to 70.0) years. Compared with DGIST patients, EGIST patients were older ( U =188.000, P =0.012], had larger tumor size [10.0 (3.0 to 29.0) cm vs. 4.0 (1.5 to 10.0) cm, U =98.500, P <0.001] and higher ratio of high risk classification [85.0% (17/20) vs. 12.5% (4/32), χ(2)=26.870, P <0.001]. Among the 20 EGIST patients, 5 were diagnosed with distal metastasis and received imatinib (400 mg/d), and the other 15 patients underwent radical resection who were included in survival analysis. All the 32 DGIST patients underwent radical resection. The median follow-up of whole group was 43 (14 to 76) months. The 3-year recurrence/metastasis-free survival rate of 15 cases undergoing radical resection in the EGIST group was 85.6%, which was lower than that of the DGIST group (88.6%), and the difference was not statistically significant ( P =0.745). There was no significant difference in the 3-year overall survival rate between the EGIST group (92.9%) and the DGIST group (100%) ( P =0.271). Conclusions: As compared to DGIST, EGIST mostly occurs in those with older age, larger tumor size and higher risk grade. The prognosis of EGIST patients after radical resection is similar to that of DGIST patients.

Background: Pediatric mastocytosis differs from adult mastocytosis in its presentation and clinical course. However, the data regarding the immunophenotypic characterization of mast cells in children are limited. Our objective was to evaluate the immunophenotype of mast cells in pediatric mastocytosis and correlate it with the clinical course., Methods: Biopsy specimens of children with cutaneous mastocytosis were retrieved from the institutions of pathology and were stained for CD25, CD2, and CD30. The percentage of mast cells and the staining intensity were correlated with the clinical data., Results: Twenty-five biopsy specimens were included in the study. Patients' average age was 15.4 at presentation and 37.5 months at biopsy performance. Clinical presentations included maculopapular cutaneous mastocytosis in 79% and mastocytoma in 21% of cases. CD25, CD2, and CD30 were positive in 60%, 44%, and 84% of the biopsy specimens, respectively. The staining score was significantly higher for CD30 as compared to those for CD25 and CD2 (P = 0.02). No correlation was found between the immunophenotype and the clinical form or course of disease., Conclusions: Our results confirm that CD30 is a sensitive marker for pediatric-onset mastocytosis. Nevertheless, its expression does not correlate with clinical subtype or clinical course. The sensitivity of CD25 is higher than that of CD2 in skin lesions., (© 2019 Wiley Periodicals, Inc.)

Aim: The aim of this study was to determine whether fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) can diagnose malignant change in benign chondroid tumors., Patients and Methods: This study included patients with clinicoradiological features of a chondroid tumor who were referred for a F-FDG PET/CT study to evaluate clinical suspicion of malignant change. Metabolic characteristics of the suspected lesion in the form of maximum standardized uptake value (SUVmax) was obtained and compared with histopathology. In patients who were treated conservatively and for whom histopathology was not available, stability of the lesion on clinical/radiological follow-up was used as reference standard. Receiver operating characteristic curve analysis was performed to obtain a SUVmax cutoff value to differentiate between benign and malignant lesions., Results: Clinical and imaging data of 66 patients was available for analysis. Malignancy was confirmed by histopathology in 40/66 (60.6%) patients with grade 2 chondrosarcomatous change seen in majority. In 26 patients, the final diagnosis was benign tumor (osteochondroma, n=19; enchondroma, n=7). Median SUVmax of malignant lesions was significantly higher compared with the benign lesions (4.0 vs. 2.1, P=0.00). A SUVmax cutoff of 3.1 could differentiate a benign lesion from those with malignant transformation with a sensitivity of 90.3% and specificity of 87% (area under the curve=0.92). Dedifferentiated sarcomas showed a significantly higher uptake than rest of the sarcoma types., Conclusion: F-FDG PET/CT can detect malignant change in benign chondroid neoplasms by showing higher metabolic activity in the area of sarcomatous transformation. It can also identify focus of dedifferentiation which has prognostic and therapeutic implications.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. We herein report a rare case of TIO in a 58-year-old Chinese man who presented with a large lump in the right palm. Clinical, biochemical, and radiological assessments were performed. Laboratory examination showed severe hypophosphatemia, phosphaturia, an elevated serum alkaline phosphatase level, and an elevated serum fibroblast growth factor 23 (FGF-23) level. Dual-energy X-ray absorptiometry showed low bone mineral density. Magnetic resonance imaging revealed an irregular mass located in the right palm and abnormal findings in several metacarpal bones. During the operation, the surgeons found that the tumor had penetrated the surrounding muscles. The tumor had unique characteristics of local tissue invasion. The patient's symptoms fully resolved and his serum phosphorus level normalized, although his serum FGF-23 level remained slightly high in the postoperative phase. Our findings suggest that in some patients with TIO, the serum phosphorus level might return to the normal range despite a relatively high postoperative serum FGF-23 level. These patients should be kept under close observation and regularly surveyed for any evidence of a residual tumor.

Shoulder lesions range from tumor-like lesions such as simple bone cysts to aggressive high-grade sarcomas. The clinical presentation is often nonspecific with shoulder pain as the primary complaint, which may lead to a delayed or missed diagnosis. Delayed diagnosis or a poorly planned biopsy of a malignant shoulder lesion can have a detrimental effect on the patient's prognosis and treatment options. Because the initial patient assessment is crucial for successful treatment, knowledge of the key features of common shoulder tumors and tumor-like conditions can help determine the diagnosis and treatment plan. This article reviews the key features and treatment options of the more commonly encountered benign and malignant shoulder bone and soft-tissue tumors and tumor-like conditions.

Fibromatoses are a group of benign connective tissue tumors characterized by the infiltrative, aggressive proliferation of well-differentiated fibroblasts, leading to frequent local recurrence. Within this heterogeneous disease group, superficial fibromatoses show slower growth and more benign infiltration of surrounding tissues than deep fibromatoses. Superficial fibromatoses relevant to dermatology include palmar, plantar, and penile fibromatosis, knuckle pads, pachydermodactyly and infantile digital fibromatosis. They present clinically with subcutaneous nodules or cords that lead to local infiltration and limited mobility of the affected areas. Treatment options vary from watchful waiting, non-invasive methods such as radiotherapy and intralesional corticosteroid/collagenase injections to radical surgical procedures. Early intervention may disrupt disease progression and may even restore functional ability. These disorders should therefore be recognized and treated early in the course of the disease., (© 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Oncogenic osteomalacia is a potentially curable condition caused by phosphaturic mesenchymal tumours. We present the case of 54-year-old woman who presented with bony pains and muscle weakness, and was erroneously treated with bisphosphonates elsewhere on the basis of Dual Energy X-ray Absorptiometry (bone density) scan that showed 'severe osteoporosis'. Further evaluation revealed the presence of hypophosphatemia, with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid avid lesion involving left mandible on PET scan. Surgical excision of lesion led to improvement in her symptoms with normalisation of phosphorus, and histopathology was diagnostic of mesenchymal phosphaturic tumour. A diagnosis of oncogenic osteomalacia was made. A repeat bone mineral density assessment done a year later showed dramatic improvement. A meticulous examination and evaluation is warranted for any patient presenting with bony pains and muscle weakness. The detection of hypophosphatemia in an elderly individual should prompt the consideration of oncogenic osteomalacia, as localisation and excision of tumour usually results in cure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Tumor-induced osteomalacia (TIO) is rare paraneoplastic disorder generally caused by small benign neoplasm. Somatostatin receptor imaging has emerged as imaging of the choice in the localization of the causative tumors in new patients with clinical diagnosis of TIO. An accurate localization of the causative tumor using somatostatin receptor imaging followed by successful surgical removal offers cure of the disease. In small percentage of the patients, however, there can be recurrent disease after the surgery. In this retrospective investigation, we tried to assess whether somatostatin receptor imaging using Tc-HYNIC-TOC (Tc-hydrazinonicotinyl-Tyr3-octreotide) is also useful in patients with recurrent TIO after initial successful surgery., Methods: The images of Tc-HYNIC-TOC images and clinical charts of total 18 patients with suspected recurrent TIO were retrospectively reviewed. The image findings were compared with the clinical chart, which include clinical follow-up and subsequent imaging and surgery., Results: Among all 18 patients, Tc-HYNIC-TOC imaging results were negative in 5 of them. Among these 5 patients with negative imaging study, the causes of recurrent symptoms and hypophosphatemia in 3 patients were eventually found unrelated to TIO. Tc-HYNIC-TOC successfully identified either recurrent causative tumors in the same location (n = 10) or different causative tumor in other locations (n = 3) in 13 patients, which rendered a sensitivity of 86.7% (13 of 15)., Conclusions: The efficacy of Tc-HYNIC-TOC imaging in the evaluation of patients with potential recurrent TIO is compatible to that with new patients who never received surgical resection for the culprit tumors. It can play an important role in known TIO patients who were suspected to have recurrent disease.

Objective: Ga-DOTATATE PET/CT is currently the most common imaging modality in localizing culprit tumors, which can result in tumor-induced osteomalacia (TIO). Fracture, which is one of the most common consequences of the TIO, can also lead to increased Ga-DOTATATE activity and potentially affect the accuracy of Ga-DOTATATE PET/CT imaging. The aim of this investigation is to evaluate whether the increased Ga-DOTATATE activity at the sites of the fracture will cause interpretation difficulty in the localizing the culprit tumor causing TIO., Method: The images of Ga-DOTATATE PET/CT scan from a total of 54 patients who had multiple foci of increased Ga-DOTATATE PET/CT on PET/CT were retrospectively analyzed. Not only was the intensity of the activity on PET but also the appearance of the activity on CT taken into consideration when the interpretation of the images occurred. The results from imaging analysis were compared with the clinical chart record. All patients had tentative clinical diagnosis of TIO., Results: The causative tumors in 53 patients were eventually identified. In 1 patient, the causative tumor was not identified. Among the 53 patients with confirmed TIO, 52 tumors were accurately localized., Conclusions: Mild activity at the sites of fracture is not a major challenging factor in the interpretation of Ga-DOTATATE PET/CT in the evaluation of TIO when both intensity on PET and morphology on CT were assessed.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phosphate wasting that results in severe hypophosphatemia, defective vitamin D metabolism, and osteomalacia. In the case reported here, maxillary TIO was not diagnosed for 6years, although initial complaints were reported when the patient was 12years old. Meanwhile she suffered from profound growth limitation, pain, weakness, and spontaneous multiple bone fractures, culminating in complete loss of ambulatory ability and severe limitation in daily activities. At age 18years, she finally received an accurate diagnosis and definitive treatment was administered. She underwent a partial maxillectomy with complete removal of the tumour, resulting in a full cure. Shortly afterwards the patient regained the ability to walk, no longer needing the wheelchair to which she had been confined. This definitive diagnosis was based on three modalities: (1) fibroblast growth factor 23 analysis (high levels of the secreted hormone were found on the left side of the maxilla in the facial vein and pterygoid plexus, pinpointing the tumour location), (2) octreotide scan, and (3) 68 Ga-DOTA-NOC-PET/CT. TIO removal via partial maxillectomy led to a complete reversal of this patient's health condition, restoring her ability to walk and function. The importance of prompt employment of these diagnostic modalities and the high level of clinical suspicion required in such cases are clear., (Copyright © 2018. Published by Elsevier Ltd.)

We investigated the usefulness of fibroblast growth factor 23 (FGF23) intraoperative assay to monitor tumor resection in patients with oncogenic osteomalacia. A 33-year-old man with 5 years' history of lumbar and pelvis pain together with multiple vertebral fractures was admitted to our hospital. He was diagnosed with ankylosing spondylitis 1 year before. Laboratory investigation showed low tubular reabsorption of phosphate (0.41 mmol/L) despite chronic hypophosphatemia (0.39/L). Increased plasma values of FGF23 (673 pg/mL; n.v. < 95 pg/mL) were also observed. A full-body CT scan showed two suspicious areas in the head of the right femur and in the right tibia; however, the Octreoscan™ showed an increased uptake of the tracer only in the femur. We decided to remove first the head femur lesion and perform intraoperative FGF23 assay to confirm tumor resection; if this had been unsuccessful, we would have extended the operation to excise the second bone lesion. FGF23 basal values and 10, 60, and 225 min after excision of the femoral head were 423, 127, 56, and 30 pg/mL, respectively. The brisk fall of FGF23 values suggested that the head femur lesion was responsible for the syndrome. Histological examination revealed a mesenchymal highly vascular tumor. This is the first report showing the possibility of intraoperative FGF23 assay to monitor tumor resection in patients with tumor-induced osteomalacia.

Phosphaturic mesenchymal tumor (PMT) is a rare, histologically distinctive neoplasm that classically presents with phosphaturia and tumor-induced osteomalacia (TIO; ie, oncogenic osteomalacia). Both the phosphaturia and the TIO are due to paraneoplastic production of FGF23 (a phosphatonin) by the neoplastic cells, which are genetically characterized by rearrangements of FN1 (most often with FGFR1, and less frequently with FGF1). However, rare cases of PMT present without phosphaturia and TIO (ie, the "nonphosphaturic" variant) and are therefore much more challenging to diagnose. Here, we report the first case of a genetically confirmed, nonphosphaturic PMT, in which the correct diagnosis was established through a combination of careful histologic evaluation, FGF23 chromogenic in situ hybridization, and fluorescence in situ hybridization testing for FN1-FGFR1., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion. Laboratory data showed hypophosphatemia and an elevated serum level of fibroblast growth factor 23 (FGF-23). Samples obtained with open biopsy showed a low-grade spindle cell neoplasm with FGF-23 positivity, identified by using immunohistochemical staining, confirming the diagnosis of a PMT mixed connective tissue variant. Curettage of the tumor was performed, and the defects were filled with bone allografts. The hip joint was reconstructed with total hip arthroplasty using a Muller support ring. To our knowledge, this report represents the first documented case of massive PMT of the acetabulum causing TIO.

Primary extragastrointestinal stromal tumor is very rare. We report a case of cervical paravertebral extragastrointestinal stromal tumor involving adjacent bones revealed by FDG PET/CT in a 66-year-old man without any gastrointestinal involvement.

Juxtacortical or surface tumors of bone are neoplasms arising from or just outside the cortex, and are composed of different histologic types. Although the imaging appearances of these lesions have similarities to their intramedullary counterparts, their location alters their radiographic and MR characteristics, creating difficulties in diagnosis. Meanwhile, several non-neoplastic lesions, such as stress reaction/stress fracture and indolent infectious processes, compound the differential diagnosis. Neoplastic juxtacortical lesions of bone have been classified into five categories: cartilaginous, fibrous, lipomatous, osseous, and metastatic tumors. Our goal in part two of this review is to illustrate the characteristic radiographic, CT and MR imaging features of various juxtacortical neoplasms, including pathognomonic imaging findings that can aid in diagnosis, and to develop an appropriate differential diagnosis for surface lesions based on imaging characteristics, lesion location and patient age., (Copyright © 2018 Elsevier Inc. All rights reserved.)