Primary diffuse large B-cell lymphoma of the cranial vault with Trousseau syndrome: a case report.

BACKGROUND: It is extremely rare for primary non-Hodgkin's lymphomas to occur singly in the cranial vault. One case diagnosed as primary diffuse large B-cell lymphoma is reported, initially misdiagnosed as metastatic skull tumor, complicated with Trousseau syndrome. CASE DESCRIPTION: The patient was a 60-year-old Japanese woman with no particular previous medical history. In a head computed tomography examination for vertigo, bone destructive skull tumor covering the right frontal, parietal, and temporal bones was incidentally discovered. As positron emission tomography indicated an abnormal accumulation in the large intestine and multiple cerebral infarctions suspicious of Trousseau syndrome were observed on magnetic resonance images, a metastatic skull tumor due to colorectal cancer was first considered. However, various tumor markers were negative, and colonoscopic biopsy indicated no colorectal abnormality. After pathological examination of the resected tumor, it was diagnosed as diffuse large B-cell lymphoma. The tumor affected muscles and skin but did not develop in the brain or the dura mater. As further general examination revealed no other abnormalities, we considered that it was primary diffuse large B-cell lymphoma in the cranial vault associated with Trousseau syndrome. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and high-dose methotrexate reduced the residual lesion; coagulation abnormalities, which are frequently associated with Trousseau syndrome, also improved. CONCLUSIONS: Skull tumors can result from a variety of malignancies, and their diagnosis may be complicated with Trousseau syndrome. However, even in cases of a single lesion in the cranial vault without invasion of the central nervous system, diffuse large B-cell lymphoma should be considered as a differential diagnosis.

Reconstruction using a frozen autograft for a skull and humeral lesion of synchronous multicentric osteosarcoma after undergoing successful neoadjuvant chemotherapy: a case report and review of the literature.

BACKGROUND: Synchronous multicentric osteosarcoma (SMOS) is a rare disease characterized by simultaneous multicentricity of intraosseous osteosarcoma without visceral involvement. SMOS, including a skull lesion, which occurs relatively rarely, and reconstruction using a frozen autograft after the excision of a lesion of SMOS has been infrequently reported previously. CASE PRESENTATION: We report an 18-year-old girl with SMOS, with lesions located in the left distal femur, right proximal humerus, and left occipital bone. Her major complaint was pain and swelling around the left knee joint. Asymptomatic lesions of the humerus and skull bone were detected on a systemic bone scan. No visceral organ metastasis was observed. A biopsy of the distal femoral lesion revealed osteosarcoma. Based on the histological findings, multiple bone lesions, and absence of visceral lesion, the clinical diagnosis of SMOS was made. After five courses of neoadjuvant chemotherapy with a regimen of doxorubicin and cisplatin, reconstruction using a tumor prosthesis following wide excision of the left distal femur was performed, and total necrosis was histologically observed in the retracted specimen. Following three cycles of adjuvant chemotherapy, tumor excision and reconstruction with a frozen autograft treated with liquid nitrogen was conducted for both lesions of the humerus and skull, rather than tumor prosthesis or synthetics, in order to retain a normal shoulder function, and to obtain a good cosmetic and functional outcome after treatment of the skull lesion. Further adjuvant chemotherapy could not be administered after the completion of the surgical treatment for all lesions because the adverse events due to chemotherapy were observed. At over 5 years after the diagnosis, she remains clinically disease-free. CONCLUSIONS: An early correct diagnosis, the proper management of chemotherapy, and surgical treatment for all lesions are essential for achieving a good clinical outcome, even in SMOS including a skull lesion. By performing reconstruction using a frozen autograft for a proximal humeral lesion and a skull lesion after confirming the good histological efficacy of neoadjuvant chemotherapy for the primary lesion, the excellent function of the shoulder joint and a good cosmetic outcome at the site of the skull lesion was acquired without complications or recurrence.

Ulcerated Infantile Hemangioma of the Hard Palate: Diagnostic Treatment With Oral Propranolol.

Infantile hemangiomas arising in the palate are rare. The authors describe a case of ulcerated infantile hemangioma of the hard palate with feeding difficulty. To our knowledge, this is the first reported case of immunohistochemically diagnosed palatal infantile hemangioma successfully treated using oral propranolol.

Therapeutic effect of Nivolumab for advanced / recurrent temporal bone squamous cell carcinoma.

OBJECTIVE: The immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC. METHOD: Chart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined. RESULTS: We examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2-54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%). CONCLUSION: We used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC.

Osteoblastoma-Like Osteosarcoma of the Cuboid and Skull: A Case Report and Review of the Literature.

Osteoblastoma-like osteosarcoma is a rare form of osteosarcoma that shares similar clinical and pathological characteristics with osteoblastoma. We describe a 12-year-old boy with osteoblastoma-like osteosarcoma of the cuboid and skull without lung involvement. Despite inadequate primary surgical treatment, the patient recovered well after wide excision and postoperative chemotherapy. We report the case for the rarity of the sites and the misleading clinical and pathological manifestation.

Stage IV Neuroblastoma with Metastatic Spread to the Mandible in a Young Child: Case Report and Review of the Literature.

BACKGROUND: Infants and young children with neuroblastoma (NB) may present with metastases. The primary tumor most commonly originates in the abdomen and metastasizes to lymph nodes, liver, and bone marrow. Infants and young children presenting with multiple skull metastases are rare. METHODS: We present a rare case of a 20-month-old child who presented with metastatic neuroblastoma and multiple skull lesions. The child responded well to induction chemotherapy followed by myeloablative busulfan/melphalan consolidation. RESULTS: The child had substantial tumor reduction after chemotherapy was started. There was a significant decrease in tumor sizes and uptake, as seen in the metaiodobenzylguanidine study. The 6-month follow-up examination showed complete remission, and the remission continues. CONCLUSIONS: Infants and young children with neuroblastoma rarely present with metastatic lesions to the skull. Even large lesions involving the skull base may be successfully treated with chemotherapy. The use of myeloablative busulfan/melphalan consolidation after induction chemotherapy can decrease the overall metastatic tumor burden. Craniofacial specialists should be aware of treatment options for these young children.

Giant Cell Lesions of the Maxillofacial Skeleton Express RANKL by RNA In Situ Hybridization Regardless of Histologic Pattern.

Maxillofacial central giant cell lesions (CGCLs) are often locally aggressive tumors in young patients that may be histologically very similar to or quite distinct when compared with giant cell tumors (GCTs) of long bones. It has been well established that GCTs express high levels of receptor activator of nuclear factor-kappa B ligand (RANKL) and are amenable to treatment with denosumab. To assess the predictive value of morphology, we evaluated CGCLs with GCT-like or non-GCT-like histology for RANKL expression by RNA in situ hybridization. Tumors were classified by clinical and radiographic criteria as aggressive or nonaggressive and histopathologically as resembling GCT or non-GCT-like. RNA in situ hybridization for RANKL mRNA was performed and scored semiquantitatively based on the magnification at which the signal was first detected. There were 17 patients (M:F=8:9) with a median age of 15 years. Nine patients were children under 18 years of age. In 10 patients, tumors were characterized as GCT-like and in 7, non-GCT-like; 6 occurred in the setting of a known associated syndrome. Of the sporadic tumors, 9/11 (82%) were classified as aggressive. Fifteen of 17 (88%) tumors strongly expressed RANKL (8/9 aggressive, 2/2 nonaggressive; 10/10 GCT-like and 5/7 non-GCT-like). Two patients with clinically aggressive CGCL, GCT-like histology and high tumor RANKL expression were identified as candidates for a trial of denosumab with notable clinical response. CGCLs demonstrate strong and diffuse RANKL mRNA expression in mononuclear stromal cells, regardless of histology or presence of an associated syndrome. Denosumab may be clinically beneficial in aggressive CGCLs.

An individual patient data meta-analysis on the effect of chemotherapy on survival in patients with craniofacial osteosarcoma.

Chemotherapy improves the survival of patients with long bone osteosarcomas. However, the benefits of chemotherapy in the treatment of craniofacial osteosarcoma (CFOS) are still controversial. We searched PubMed and EMBASE from February 1997 to December 2016 to identify studies on CFOS. The individual patient data of these studies were pooled into a meta-analysis. Univariate and multivariate survival analyses were performed. Thirteen studies with a total of 184 patients met our inclusion criteria. Positive resection margin was a poor prognostic factor for CFOS in the univariate and multivariate survival analyses. Chemotherapy improved overall survival (OS) and disease-specific survival (DSS) in patients with CFOS who had tumors in the maxilla, positive resection margins, or high-grade tumors. Patients with local tumor recurrence had better OS and DSS when treated with chemotherapy. Chemotherapy improves survival in patients with CFOS with adverse factors, such as tumors with positive margins, high-grade tumors, and recurrent tumors.

Myeloid sarcoma involving the greater wing of the sphenoid bone and additional skeletal sites presenting with unilateral proptosis and fevers.

We report a case of myeloid sarcoma with multifocal skeletal involvement, including the greater wing of the sphenoid bone. A 23-month-old boy presented with left-sided proptosis and fevers, and was found to have an infiltrative mass involving the left sphenoid bone on orbital imaging. Full body imaging further demonstrated multiple bony lesions in the pelvis, thoracic and lumbar vertebrae, bilateral femura, and left humerus, and biopsies of the humerus were consistent with myeloid sarcoma. The patient was started on a standard chemotherapy regimen and is responding well. Myeloid sarcoma presenting with proptosis due to sphenoid bone involvement with simultaneous multifocal skeletal involvement is very uncommon and highlights the importance of biopsy for establishing a definitive diagnosis.

Co-existence of Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions: A case report.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder resulting from dysregulated clonal proliferation of Langerhans cells. Reticulohistiocytosis (RH) is another rare histiocytosis caused by the proliferation of histiocytes other than Langerhans cells. Co-existence of LCH and RH in different organs and in the same skin area has not been reported. We present the case of a 20-year-old woman who initially had co-existing bone LCH and cutaneous RH. After 1 year of chemotherapy with cytarabine, bone LCH significantly improved but cutaneous LCH developed in the same area where cutaneous RH was, resulting in hybrid LCH and RH of the skin. This unique history provides some evidence to support the theory that LCH and RH originate from the same stem cells and subsequently develop into hybrid LCH and RH of the skin in a cytokine environment influenced by chemotherapy. Repeat skin biopsies may be considered for adjusting treatment regimens in LCH patients whenever pre-existing skin lesions progress.

Multiple myeloma with pathologically proven skull plasmacytoma after a mild head injury: Case report.

RATIONALE: MM is a malignant tumor originating from the plasma cells of the bone marrow. Central nervous system myelomatosis is very rare and may be a complication of MM. PATIENT CONCERNS: A 60-year-old man presented with a slowly growing soft mass at his right frontal scalp after a mild head injury 6 months ago. DIAGNOSES: Neuroradiological examinations revealed a solid intracranial-extracranial mass with an osteolytic lesion in the skull. Histopathological examination showed skull plasmacytoma, and postoperative examinations revealed multiple myeloma. INTERVENTIONS: The tumor was completely removed and the skull defect repaired with the titanium mesh. Then, chemotherapy was initiated after surgery with bortezomib and dexamethasone. OUTCOMES: The patient received eight chemotherapies within one year after surgery. LESSONS: Despite a history of head injury, a differential diagnosis should be kept in mind during the diagnosis of solid intracranial-extracranial masses, especially in the presence of osteolytic skull at the lesioned site.

Osteogenic sarcoma of the skull: long-term outcome of a rare tumor.

BACKGROUND: Osteogenic sarcoma of the skull is uncommon and long-term outcome is not well defined. We review the literature and present a pediatric case of calvarial osteogenic sarcoma with good long-term oncological and cosmetic outcome and excellent quality of life. This case presented major surgical challenges, which are detailed. CASE DESCRIPTION: A 6-year-old boy presented with a painless 5 cm × 5 cm lump over the vertex region. He was neurologically normal. Imaging showed an extensive bony lesion with intradural extension. After incisional biopsy showed probable low grade osteosarcoma, a complete en bloc resection with margins was attempted via a concentric craniotomy around the lesion after embolization to reduce blood loss. Invasion of the brain by the tumor precluded the complete en bloc resection, but gross total resection was achieved. The final pathology was consistent with a low-grade osteosarcoma and adjuvant chemotherapy was provided. Follow-up for 8 years has shown no recurrence with good cosmetic and functional outcome.

Double-Hit Lymphoma (MYC and BCL6) with Involvement of Skull and Adnexal Lesions: A Case Report and a Review of the Literature.

BACKGROUND Double-hit lymphomas (DHL) belong to a category of very aggressive lymphomas characterized by MYC translocation and either BCL2, or less commonly, BCL6 translocations. Those with BCL6 translocations have a predilection for rare extranodal sites such as the gastrointestinal tract, nasopharynx, and tonsils. Involvement of the skull and adnexal structures is rare. Here we report a case of a young female with both skull and adnexal involvement. CASE REPORT A 20-year-old female who presented with hypercalcemia was found to have adnexal, skull, and jaw masses. Workup revealed a stage IV high grade B-cell lymphoma (HGBL) with MYC and BCL6 rearrangements. She was subsequently treated with R-EPOCH and attained complete remission 9 months after her initial presentation. To the best of our knowledge, our patient represents the first reported case of skull and adnexal involvement in HGBL with MYC and BCL6 rearrangement. CONCLUSIONS Rare extranodal presentations of HGBL with MYC and BCL6 rearrangement should be considered in the differential diagnosis of masses found in unusual sites such as the skull and adnexa. Due to their aggressive nature, early and prompt recognition of these lymphomas is essential for timely administration of appropriate therapy.

Durable clinical remission of a skull metastasis under intralesional Viscum album extract therapy: Case report.

BACKGROUND: Skull metastases are rare, they can eventually cause pain, and can invade the brain. Viscum album extracts (VAEs) are used as an adjuvant treatment in cancer. METHODS AND RESULTS: A 68-year-old patient with rectal cancer presented with lung metastases, and metastases to multiple bone sites, the chest wall, and the liver were later identified. Histological examination of one of the bone lesions revealed an additional thyroid carcinoma. An osteolytic parietal bone lesion progressed to a painful metastasis of the skull despite radiotherapy and chemotherapy. The VAEs were applied weekly into the metastasis, followed by pain relief and softening of the lesion. The lesion partially regressed (>50%) after 8 months of continued VAE treatment and remained stable for 2 years. CONCLUSION: This case shows a durable clinical remission of a skull metastasis under VAE. Further investigations of intratumoral VAE treatment seem worthwhile-especially in symptomatic skull metastases not responding to radiotherapy or systemic therapies.

Congenital Calvarial Hemangioma.

OBJECTIVES: The authors describe a case of congenital calvarial hemangioma successfully managed using propranolol therapy. Presenting symptoms, radiological and pathological features, differential diagnosis, and management of this rare congenital mass are described. CASE PRESENTATION: A 2-year-old boy presented with a 1-year history of a growing right parietal skull mass. No obvious etiology was apparent. No focal neurological deficits or associated craniofacial anomalies were identified. Plain film imaging demonstrated focal thickening of the right parietal bone with internal trabeculations in a sunburst appearance. Computed tomography (CT) scan showed bone thickening with coarsening of the bony trabeculae, minor irregularity of the outer table, unaffected inner table, and no evidence of aggressive features. A diagnostic biopsy of the lesion was performed in the operating room. Microscopic examination was consistent with hemangioma. Based on histological and radiological features of the lesion, it was identified as a cavernous hemangioma. Medical treatment utilizing propranolol was initiated for over 3 years with interval reduction in the lesion size. MRI head following treatment with propranolol demonstrated reduction of the mass compared to preoperative imaging. CONCLUSIONS: Although a rare entity, it is important to consider congenital calvarial hemangioma in the differential diagnosis of slow growing skull lesions due to the possibility of complications as a result of the hemangioma's intracranial extension, and the potential for treatment. En bloc resection has classically been described as a treatment for such lesions, although our case demonstrates that medical treatment with propranolol therapy may be appropriate in certain situations.

Primary cranial vault lymphoma.

A 49-year-old woman presented to our institution with a progressive frontal scalp swelling for one year. Incisional biopsy was performed and histological examination showed diffuse large B-cell lymphoma. The case details and management were discussed.

Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?

BACKGROUND: Giant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly 'GCTB-schedule' (120 mg per 12/year, 1440 mg total dose/year) are lacking. METHODS: Patients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated. RESULTS: Ninety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6-45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13-76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9-115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7-15 months). ADVERSE EVENTS: Overall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84-100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%). CONCLUSIONS: Prolonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB.