Single-cell RNA sequencing reveals the cellular and molecular heterogeneity of treatment-naïve primary osteosarcoma in dogs.

Osteosarcoma (OS) is a heterogeneous, aggressive malignancy of the bone that disproportionally affects children and adolescents. Therapeutic interventions for OS are limited, which is in part due to the complex tumor microenvironment (TME). As such, we used single-cell RNA sequencing (scRNA-seq) to describe the cellular and molecular composition of the TME in 6 treatment-naïve dogs with spontaneously occurring primary OS. Through analysis of 35,310 cells, we identified 41 transcriptomically distinct cell types including the characterization of follicular helper T cells, mature regulatory dendritic cells (mregDCs), and 8 tumor-associated macrophage (TAM) populations. Cell-cell interaction analysis predicted that mregDCs and TAMs play key roles in modulating T cell mediated immunity. Furthermore, we completed cross-species cell type gene signature homology analysis and found a high degree of similarity between human and canine OS. The data presented here act as a roadmap of canine OS which can be applied to advance translational immuno-oncology research.

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

A retrospective Italian Society of Veterinary Oncology (SIONCOV) study of 56 cats with appendicular osteosarcoma.

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi-institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow-up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty-six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow-up, resulting in an overall metastatic rate of 30%. Forty-nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour-specific survival (TSS) were not reached. One- and 2-year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1- and 2-year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P < .001) and TSS (P = .001) compared with non-operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour-related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain.

Reconstruction surgery using polypropylene mesh after extensive resection of a costal osteosarcoma in a dog.

Osteosarcoma is the most common tumour that develops in the chest wall of dogs; an extensive excision is the treatment of choice. Various methods have been reported for reconstruction of chest wall defects following extensive excision. The objective of this report was to describe the complete resection of an extensive costal osteosarcoma with an extended resection of the ribs and part of the diaphragm in a dog. An 11-year-old neutered, male, miniature pinscher was presented with dyspnoea: An extensive mass was observed, stretching from the right chest wall to the abdominal wall. On computed tomography, the mass originated from the right 9th rib and exceeded the 6th rib on the cranial side and the 13th rib on the caudal side; it was compressing the lungs, diaphragm, liver, stomach and duodenum. When the patient's condition was medically stabilized, the tumour was removed from the right 9th rib. In consideration of the surgical margin, the 5th-13th ribs were excised, and the tumour was resected with the thoracoabdominal wall and part of the diaphragm. The missing thoracoabdominal wall and section of the diaphragm were reconstructed using two sheets of a polypropylene mesh. Postoperatively, flail chest was observed, although dyspnoea was not observed in the patient. Histopathological examination confirmed the diagnosis of osteosarcoma with a clean margin. Although 60.6 months have passed post-surgery, no metastasis has reoccurred. In this case, complete resection and reconstruction of the chest wall and diaphragm were achieved using a polypropylene mesh without fatal postoperative complications, despite extensive osteosarcoma resection.

Osteosarcoma of the wing in a sulfur-crested cockatoo.

A 26-year-old female sulfur-crested cockatoo (Cacatua galerita) was evaluated for vocalizing through the night and extending her right wing. Physical examination revealed a large, firm mass extending from the humerus to the distal aspect of the elbow. Computed tomography confirmed a large aggressive mass of the right distal humerus with a large soft tissue component, severe osteolysis, and adjacent periosteal proliferation. Fine-needle aspirates of the mass were most compatible with sarcoma, and osteosarcoma was prioritized. An unstained slide was treated with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase (NBT/BCIP) substrate for ALP detection and was strongly positive, confirming a diagnosis of osteosarcoma. A month later, the patient underwent wing amputation and arrested during recovery from anesthesia. Post-mortem examination and histopathology were consistent with osteosarcoma. This case report highlights a rare occurrence of osteosarcoma in a cockatoo as well as its cytologic and histologic features. Additionally, this report provides support for NBT/BCIP application in ALP-expressing tumors, a cytochemical stain that has been minimally investigated in avian species.

Outcomes of 35 dogs with craniomaxillofacial osteosarcoma treated with stereotactic body radiation therapy.

Canine craniomaxillofacial osteosarcoma (OSA) is most commonly treated surgically; however, in cases where surgery is not feasible or non-invasive treatment is desired, stereotactic body radiation therapy (SBRT) may be elected for local tumour control. In this study, we evaluated 35 dogs treated with SBRT. Nine dogs (26%) had calvarial, seven (20%) had mandibular and 19 (54%) had maxillary OSA. Median time to first event (TFE) was 171 days, and overall median survival time (MST) was 232 days. Site-specific MSTs were 144 days for mandible, 236 days for calvarium and 232 days for maxilla (p = .49). Pulmonary metastatic disease was observed in 12/35 (34%) patients and was detected pre-SBRT in six dogs (17%) and post-SBRT in the remaining six dogs (17%). Eighteen adverse events post-SBRT were documented. Per veterinary radiation therapy oncology group criteria, five were acute (14%) and three were late (9%) grade 3 events. Neurological signs in two dogs were suspected to be early-delayed effects. Cause of death was local progression for 22/35 (63%) patients, metastasis for 9/35 (26%) patients and unknown for four. On univariate analysis, administration of chemotherapy was associated with a longer TFE (p = .0163), whereas volume of gross tumour volume was associated with a shorter TFE (p = .023). Administration of chemotherapy and five fractions versus single fraction of SBRT was associated with increased survival time (p = .0021 and .049). Based on these findings, a treatment protocol incorporating chemotherapy and five fractions of SBRT could be considered for dogs with craniomaxillofacial OSA electing SBRT with careful consideration of normal tissues in the field.

Updates in Osteosarcoma.

Clinical care of osteosarcoma (OSA) in dogs has seen little change during the past 2 decades, relying on amputation and platinum-based chemotherapy for pain control and survival. Recent advancements offer hope for improved outcomes. Genomic research reveals shared genetic abnormalities between canine and human OSA. Multidimensional imaging provides valuable staging and prognostic information. Limb-sparing approaches including stereotactic body radiation therapy are routine. Ablative therapies such as microwave ablation and histotripsy show promise. Immunotherapy including cell therapy and immune checkpoint inhibition are available. Radiopharmaceuticals are tuned to target OSA cells directly. These innovations may enhance treatment and prognosis for dogs with OSA.

Radiotherapy in combination with exenteration and partial orbitectomy for orbital multilobular tumor of bone in a Cocker Spaniel.

Background: Multilobular tumor of bone or multilobular osteochondrosarcoma is a tumor of flat bone in the skull. The treatment of choice for a multilobular tumor of bone is local aggressive surgical excision. Case Description: A female Cocker Spaniel dog aged 11 years presented with a history of globe displacement of the right eye for 3 months. Ophthalmic examination revealed exophthalmos, third eyelid protrusion, and slightly increased intraocular pressure OD (oculus dexter; right eye). Computed tomography (CT) revealed a mass effect in the right retrobulbar, maxilla, zygomatic, and temporal areas. Right zygomatic and temporal bone lysis were observed. Physical examination, hematology, and blood chemistry results were within normal limits. Exenteration with zygomatic arch removal was performed. During surgery, a firm 2-lobed mass (4.8 × 3.7 and 1.6 × 1.4 cm) adhered to the mandible was found in the retrobulbar area OD. Histopathological findings revealed a multilobular tumor of bone. CT imaging was performed for the remaining tumor and an extended part of the right retrobulbar mass was found. Hypofractioned radiotherapy with 6 fractions of 6 Gy was performed on days 0, 7, 14, 21, 28, and 35. At 1-month and 4-month follow-up inspections, the mass gradually reduced in size. At 8 months and 11 months after radiotherapy, the mass was unremarkable. The dog was alert during all follow-up periods to 1 year and 8 months after hypofractioned radiotherapy combined with exenteration and partial orbitectomy. Conclusion: Hypofractioned radiotherapy combined with exenteration and partial orbitectomy extended the patient's survival and decreased the size of the remaining tumor for the management of orbital multilobular tumor of bone in this dog for at least 1 year and 8 months.

Single-Nuclei Multiome (ATAC + Gene Expression) Sequencing of a Primary Canine Osteosarcoma Elucidates Intra-Tumoral Heterogeneity and Characterizes the Tumor Microenvironment.

Osteosarcoma (OSA) is a highly aggressive bone tumor primarily affecting pediatric or adolescent humans and large-breed dogs. Canine OSA shares striking similarities with its human counterpart, making it an invaluable translational model for uncovering the disease's complexities and developing novel therapeutic strategies. Tumor heterogeneity, a hallmark of OSA, poses significant challenges to effective treatment due to the evolution of diverse cell populations that influence tumor growth, metastasis, and resistance to therapies. In this study, we apply single-nuclei multiome sequencing, encompassing ATAC (Assay for Transposase-Accessible Chromatin) and GEX (Gene Expression, or RNA) sequencing, to a treatment-naïve primary canine osteosarcoma. This comprehensive approach reveals the complexity of the tumor microenvironment by simultaneously capturing the transcriptomic and epigenomic profiles within the same nucleus. Furthermore, these results are analyzed in conjunction with bulk RNA sequencing and differential analysis of the same tumor and patient-matched normal bone. By delving into the intricacies of OSA at this unprecedented level of detail, we aim to unravel the underlying mechanisms driving intra-tumoral heterogeneity, opening new avenues for therapeutic interventions in both human and canine patients. This study pioneers an approach that is broadly applicable, while demonstrating significant heterogeneity in the context of a single individual's tumor.

Apocrine carcinoma-and-malignant myoepithelioma in a dog: a case of simultaneous malignant progression of both luminal epithelium and myoepithelium.

A 9-y-old male Boxer dog developed a mandibular skin tumor, which histologically had a locally invasive growth pattern composed of bilayered structures of inner eosinophilic cuboidal tumor cells and outer clear polygonal tumor cells with cytoplasm containing glycogen granules. Both cell populations gradually changed from low-grade morphologic features to highly anaplastic ones. Immunohistochemically, the eosinophilic tumor cells were positive for cytokeratin 8, a useful marker for luminal epithelial cells. In contrast, the clear tumor cells expressed several myoepithelial markers, including α-smooth muscle actin, p63, and cytokeratin 14. Based on these histologic and immunohistochemical characteristics, we diagnosed this apocrine sweat gland tumor as a carcinoma-and-malignant myoepithelioma with high-grade transformation of both luminal and myoepithelial cells. Our case may be a helpful reference for the histogenesis of carcinoma-and-malignant myoepithelioma, in which both the luminal epithelial and myoepithelial components are malignant.

A case of a dog with mandibular extraskeletal osteosarcoma after long-term puncture extirpation of the salivary gland cyst in the mandible.

Background: Extraskeletal osteosarcoma, unlike skeletal osteosarcoma, is a rare malignant mesenchymal tumor with a soft tissue primary that has been reported to occur in a variety of soft tissues. Case Description: The case is a 14-year-old, unneutered male Miniature Pinscher, weighing 6.7 kg, who had been treated medically for more than 5 years with a management strategy of puncture extirpation of a salivary gland cyst in the mandible; 1 month earlier, the fluid retention could not be removed, and after a computerized tomography scan showed no lesion in the mandible adjacent to the mass lesion, surgical resection was performed. Conclusion: Previous reports of extraskeletal osteosarcoma from the salivary glands in dogs have been rare. However, treatment of a salivary gland cyst in the mandible by long-term puncture extirpation may be a potential predisposing factor for the development of extraskeletal osteosarcoma around the mandible.

Osteosarcoma in a free-living yellow armadillo (Euphractus sexcinctus).

An adult male free-living yellow armadillo (Euphractus sexcinctus) was found by hunters and referred for clinical evaluation because of a tumour-like lesion on the carapace. The animal was lethargic and weak with severe dehydration, enophthalmos and cachexia, and was euthanized because of its very poor clinical condition. Necropsy revealed a whitish, exophytic, irregular and moist mass (7 × 6.5 × 1.5 cm) in the caudal third of the carapace. On cut section, the mass was hard, compact, irregular and whitish. Histopathology revealed a densely cellular, expansive, poorly delimited neoplasm composed of malignant mesenchymal cells arranged in islands and cords, interspersed by numerous areas of irregularly mineralized osteoid matrix. Neoplastic cells were intensely immunolabelled for vimentin. The diagnosis of a high-grade osteosarcoma of osteoblastic subtype was based on the clinical, gross, histopathological and immunohistochemical findings. This first report of an osteosarcoma in an armadillo expands the list of armadillo diseases and will assist the management of these animals by veterinarians.

In vivo prostate cancer research: Key interspecies prostate anatomical features for translation medicine.

Prostate cancer (PCa) is a prevalent malignancy affecting men worldwide. Animal models play a crucial role in studying PCa pathology and discovering novel approaches to prevent, detect and treat this disease. However, the challenge of translational medicine is the limited reproducibility and inadequate recapitulation of human conditions in animal models. Therefore, a comprehensive understanding of the macroscopic and microscopic anatomy of the prostate gland among distinct animal species is essential for better translating research findings to clinical practice. This review aims to compare and describe the macroscopic and microscopic anatomy of the prostate gland in humans, rats, and dogs, emphasizing the relevant features. Despite the anatomical differences between these species, rats are a valuable model to study human prostate diseases, once they share some features implicated in carcinogenesis in humans. Dogs, on the other hand, are considered the best model for studying PCa due to the development of spontaneous cancer with a higher incidence when compared with other animals and the development of bone metastases. Moreover, the lymphatic system and the sentinel lymph node role and mapping are similar in dogs and humans. However, it is important to recognize that no animal model can directly mimic all aspects of PCa as the human prostate is anatomically different from that of rats and dogs. Therefore, it is essential to analyze and understand the intra- and interspecies variability when translating research findings into clinical practice. This review highlights the importance of a thorough understanding of the anatomical differences between the prostate gland in humans, rats, and dogs when selecting the appropriate animal model for studying PCa.

Transcriptional profiling of canine osteosarcoma identifies prognostic gene expression signatures with translational value for humans.

Canine osteosarcoma is increasingly recognized as an informative model for human osteosarcoma. Here we show in one of the largest clinically annotated canine osteosarcoma transcriptional datasets that two previously reported, as well as de novo gene signatures devised through single sample Gene Set Enrichment Analysis (ssGSEA), have prognostic utility in both human and canine patients. Shared molecular pathway alterations are seen in immune cell signaling and activation including TH1 and TH2 signaling, interferon signaling, and inflammatory responses. Virtual cell sorting to estimate immune cell populations within canine and human tumors showed similar trends, predominantly for macrophages and CD8+ T cells. Immunohistochemical staining verified the increased presence of immune cells in tumors exhibiting immune gene enrichment. Collectively these findings further validate naturally occurring osteosarcoma of the pet dog as a translationally relevant patient model for humans and improve our understanding of the immunologic and genomic landscape of the disease in both species.

Patterns of metastatic progression and association with clinical outcomes in canine osteosarcoma: A necropsy study of 83 dogs.

Osteosarcoma is a highly metastatic primary bone tumour that occurs spontaneously in both pet dogs and humans. Patterns of metastasis to organs beyond the most common site (lung) are poorly characterised and it is unknown whether specific associations between patterns of metastatic progression and patient features exist. This retrospective study characterised the necropsy findings of 83 dogs receiving standardised therapy and clinical monitoring in a prospective clinical trial setting to document patterns of metastasis and correlate outcomes with these patterns and other patient and tumour-specific factors. A total of 20 different sites of metastasis were documented, with lung as the most common site, followed by bone, kidney, liver, and heart. Two distinct clusters of dogs were identified based on patterns of metastasis. There was no significant association between site of enrollment, trial arm, sex, serum alkaline phosphatase (ALP) activity, or tumour location and clinical outcomes. A second cancer type was identified at necropsy in 10 dogs (10/83; 12%). These data showcase the extensive nature of osteosarcoma metastasis beyond the lung and provide a benchmark for clinical monitoring of the disease. Further, this study provides insight into transcriptional features of primary tumours that may relate to a propensity for osteosarcoma metastasis to specific organs and tissues.

Vulval apocrine adenocarcinoma with tumour-associated eosinophilia in a cat.

A 10-year-old, spayed female, Domestic Shorthaired cat was referred for surgical removal of a mass on the left vulval fold. An impression smear revealed mixed cell inflammation, with eosinophils predominating focally, and a concurrent bacterial infection, suggesting a primarily inflammatory lesion. However, cytology of a fine-needle aspirate of the mass revealed a neoplastic epithelial cell population, confirmed on histopathology as an apocrine vulval adenocarcinoma with lymphatic invasion and marked tumour-associated tissue eosinophilia. One month after surgical excision of the mass, the cat developed inguinal metastatic lymphadenopathy and chemotherapy was initiated. The patient ultimately developed marked peripheral lymphadenomegaly and was euthanized due to concerns for overall quality of life and comfort. This case highlights that neoplasia should be a consistent differential diagnosis for eosinophilic infiltrates/inflammation. The distinct appearance of the two cytological samples in this case stresses the need for sampling of different sites of a lesion and the importance of not relying on superficial impression smears for clinical management and prognosis.

Phase I evaluation of CycloSam® (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma.

153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

A single-cell RNA sequencing atlas of circulating leukocytes from healthy and osteosarcoma affected dogs.

Translationally relevant animal models are essential for the successful translation of basic science findings into clinical medicine. While rodent models are widely accessible, there are numerous limitations that prevent the extrapolation of findings to human medicine. One approach to overcome these limitations is to use animal models that are genetically diverse and naturally develop disease. For example, pet dogs spontaneously develop diseases that recapitulate the natural progression seen in humans and live in similar environments alongside humans. Thus, dogs represent a useful animal model for many areas of research. Despite the value of the canine model, species specific reagent limitations have hampered in depth characterization of canine immune cells, which constrains the conclusions that can be drawn from canine immunotherapy studies. To address this need, we used single-cell RNA sequencing to characterize the heterogeneity of circulating leukocytes in healthy dogs (n = 7) and osteosarcoma (OS) affected dogs (n = 10). We present a cellular atlas of leukocytes in healthy dogs, then employ the dataset to investigate the impact of primary OS tumors on the transcriptome of circulating leukocytes. We identified 36 unique cell populations amongst dog circulating leukocytes, with a remarkable amount of heterogeneity in CD4 T cell subtypes. In our comparison of healthy dogs and dogs with OS, we identified relative increases in the abundances of polymorphonuclear (PMN-) and monocytic (M-) myeloid-derived suppressor cells (MDSCs), as well as aberrations in gene expression within myeloid cells. Overall, this study provides a detailed atlas of canine leukocytes and investigates how the presence of osteosarcoma alters the transcriptional profiles of circulating immune cells.

Multilobular tumor of bone arising from the palatomaxillary suture line in the skull of a dog.

A 6-year-old neutered male bloodhound dog was presented for surgical evaluation of an intraoral hard palate mass noted during a routine dental cleaning performed by the primary veterinarian. Computed tomography (CT) of the skull revealed a well-defined, multilobular, mineralized mass with a coarse, granular appearance, centered along the palatomaxillary suture extending into both the nasal and oral cavities. Bilateral caudal maxillectomy was performed for curative-intent resection of the tumor. The histopathology of the mass was consistent with a completely excised palatomaxillary multilobular tumor of bone (MLTB). This is apparently the 1st successful report of surgical excision of an MLTB associated with the palatomaxillary suture line. Key clinical message: Our findings emphasized that MLTB should be considered as a differential diagnosis for masses arising in the location of cranial sutures, and a definitive diagnosis can be made postoperatively with histopathology of the mass.

Tumeur osseuse multi-lobulaire résultant de la ligne de suture palato-maxillaire dans le crâne d'un chien. Un chien Saint-Hubert mâle castré de 6 ans a été présenté pour évaluation chirurgicale d'une masse intrabuccale du palais dur notée lors d'un nettoyage dentaire de routine effectué par le vétérinaire initial. La tomodensitométrie (CT) du crâne a révélé une masse minéralisée multi-lobulaire bien définie avec un aspect grossier et granuleux, centrée le long de la suture palato-maxillaire s'étendant dans les cavités nasale et buccale. Une maxillectomie caudale bilatérale a été réalisée pour une résection à visée curative de la tumeur. L'histopathologie de la masse était compatible avec une tumeur osseuse multi-lobulaire palato-maxillaire complètement excisée (MLTB). Il s'agit apparemment du premier rapport réussi d'excision chirurgicale d'une MLTB associé à la ligne de suture palato-maxillaire.Message clinique clé :Nos résultats ont souligné que la MLTB doit être considérée comme un diagnostic différentiel pour les masses apparaissant à l'emplacement des sutures crâniennes, et un diagnostic définitif peut être posé en postopératoire avec l'histopathologie de la masse.(Traduit par Dr Serge Messier).