An unusual case of extra-nodal interdigitating dendritic cell neoplasm: sarcoma or not?

INTRODUCTION: Interdigitating dendritic cell sarcoma (IDCS) represents an extremely rare neoplasm frequently originating from T-cell- associated dendritic antigen-presenting cells normally populating the paracortex of lymph nodes. Diagnosis is challenging due to the rarity of this neoplasm and the overlapping features with the other primary and metastatic spindle cell neoplasm, even more, when localized in an extra-nodal site. PATIENTS AND METHODS: Herein we report a case of 48 Years old woman with a six-month history of centimetric, quiet painful mass of the philtrum without other significant comorbidity. RESULTS: Histological report showed a proliferation of quiet bland spindle to plump cell, scattered multinucleated giant cell in a subtle background of lymphocytes. IHC study displays only positivity for S-100 and fine, granular scattered cytoplasmatic stain for CD68; all dendritic IHC markers were negative. Morphological and immunohistochemical analyses were consistent with extra-nodal Interdigitating Dendritic Cell Neoplasm. CONCLUSION: Interdigitating Dendritic Cell Sarcoma is a rare and challenging entity with a variable prognosis. We present a case of extra-nodal IDCS whit low worrisome histological features, emphasizing the need for further efforts to better definitely this rare neoplasm ad its potential for malignancy.

CIC-rearranged sarcoma presenting with superior vena cava syndrome: case report.

CIC-rearranged sarcomas are rare mesenchymal neoplasms belonging to the family of undifferentiated small round cell sarcomas. This report details the case of a 45-year-old man presenting with symptoms of mediastinal compression, radiological diagnosis of a mediastinal mass and rapid evolution to full-blown superior vena cava syndrome. The emergency was successfully managed with a pharmacological approach. Formulation of a pathological diagnosis of CIC-rearranged sarcoma was initially supported by fluorescence in situ hybridisation findings and later validated by next-generation sequencing, which showed CIC-DUX4 gene fusion. A chemotherapy regimen was started with immediate benefits for the patient. The spectrum of pathological entities able to cause superior vena cava syndrome is wide, and recognition of rare causes is important to tailor the therapeutic approach to the specific disease. This is, to the best of our knowledge, the first report of CIC-rearranged sarcoma presenting with superior vena cava syndrome.

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre.

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1-9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.

Primary intraosseous solitary fibrous tumor: an extremely rare case report and brief review of the literature.

Solitary fibrous tumor (SFT), a rare mesenchymal neoplasm of fibroblastic origin, was initially discovered in the mediastinal pleura and then described in many extra-pleural sites.The reports of primary solitary fibrous tumor of bone are extremely rare and only a few cases have been previously mentioned in the literature, most of which in flat and short bones.Here we present the case of a 53-year-old female, who was referred to the emergency department of a peripheral hospital after an accidental fall. Imaging studies revealed an intertrochanteric fracture with an underlying intramedullary lytic lesion. A biopsy was performed and a diagnosis of Ewing sarcoma was initially suggested. She arrived at our hospital where we reevaluated the case. The biopsy was reviewed and a diagnosis of intraosseous SFT was proposed. She underwent en-block resection of the proximal right femur.Primary SFTs of the bone are, like in our case, easily misdiagnosed due to the low specificity of the imaging studies and the extreme rarity of the localization. An accurate diagnosis and early resection are very important and with careful long-term follow-up is essential, particularly in those who with malignant behavior, for the early detection of possible recurrence or metastasis.

[18F]FDG PET/CT quantitative parameters for the prediction of histological response to induction chemotherapy and clinical outcome in patients with localised bone and soft-tissue Ewing sarcoma.

OBJECTIVE: The application of [18F]FDG PET/CT in predicting histologic response to induction chemotherapy in patients with Ewing sarcoma (EWS) has been proposed using the values of pre-post treatment SUVmax as a referral parameter, although with heterogeneous results. The aim of this retrospective study was to evaluate the diagnostic accuracy of [18F]FDG PET/CT volumetric parameters (metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) as compared to SUVmax to predict response to chemotherapy and clinical outcome in patients with localised EWS of bone and soft-tissue. METHODS: Twenty-eight patients with non-metastatic EWS of bone (n = 20) and soft tissues (n = 8) who underwent a [18F]FDG PET/CT scan before (PET1) and after induction chemotherapy (PET2) were enclosed in the analysis. Values of PET metrics (SUVmax, MTV, TLG) at diagnosis and after neoadjuvant chemotherapy as well as the percentage change between PET1 and PET2 (ΔSUV, ΔMTV and ΔTLG) were correlated to histological response and to progression-free survival (PFS). RESULTS: ΔTLG (cut-off: -60%) is the best predictor for histologic response with 100% sensitivity and 77.8% specificity. MTV1 > 33.4 cm3 and TLG1 > 112 were also associated with a favourable histologic response (sensitivity 80% and specificity 77.8% for both). On multivariate analysis, SUV2 (> 3.3) and ΔTLG (< -18%) were independent predictors of worse PFS. CONCLUSIONS: [18F]FDG PET/CT could accurately predict histologic response to neoadjuvant chemotherapy in patients with EWS, also showing a possible prognostic value for future disease relapse. KEY POINTS: • The variation of the PET parameter tumour lesion glycolysis (TLG) can predict the histologic response to induction chemotherapy (sensitivity 100%, specificity 77.8%), in patients with Ewing sarcoma. • The percentage variation of TLG and the value of the SUVmax at PET scan after chemotherapy show a prognostic role for future disease relapse. The combination of both the parameters identifies three prognostic classes of patients with low, intermediate and high risk of disease relapse.

Uncommon retroperitoneal tumour: follicular dendritic cell sarcoma.

INTRODUCTION: Retroperitoneal Follicular Dendritic Cell Sarcomas represents rare tumours with aggressive biologic behaviour. Accurate diagnosis requires a combination of both morphological and immunohistochemical analyses. PATIENTS AND METHODS: A 61-year-old man was referred to our Department with a left perinephric mass. Computed tomography scan showed a 5.5 cm circumscribed mass in front of the left renal vein abutting the first jejunal loop, with moderate heterogeneous contrast enhancement. Positron emission/computed tomography showed increased focal uptake in the lesion. RESULTS: A retroperitoneal tumor located behind the first jejunal loop was found at laparotomy, encompassing the superior mesenteric vessels. Excision with en-bloc segmental small bowel resection was performed. Morphological and immunohistochemical analyses were consistent with Follicular Dendritic Cell Sarcoma. CONCLUSIONS: Complete surgical resection in specialized multidisciplinary centers represents the treatment of choice for both primary or recurrent lesions since there is still no consensus on the role of adjuvant radio-chemotherapy.

Myxoid Liposarcoma Metastasizing to the Parotid Gland.

Localization of metastases into the parotid gland is a very uncommon event. Usually they arise from primary tumors located in the head and neck, mainly melanoma or epidermoid carcinoma of the skin, while other histotypes, from others anatomical districts, hardly have a metastatic spread to the parotid. Myxoid liposarcoma (MLS) is a rare malignant tumor of the soft tissue that mainly occurs in the extremities, representing the second most common subtype of liposarcoma. Although it is typical for liposarcomas to metastasize to the lungs, it is known that MLS can spread also to extra pulmonary sites. The authors report a case of myxoid liposarcoma of the left thigh in a 64-year-old man, with an unusual metastatic double presentation to the contralateral forearm first and to the parotid gland then. MLS with metastatic disease to the parotid gland is an extremely rare event with very few cases reported in the English literature.

Cervical lymphadenopathy: can the histogram analysis of apparent diffusion coefficient help to differentiate between lymphoma and squamous cell carcinoma in patients with unknown clinical primary tumor?

PURPOSE: To retrospectively evaluate the value of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck nodes. METHODS: A total of 39 patients, 20 affected by lymphoma and 19 affected by metastatic non-nasopharyngeal SCC, were included in this retrospective study. All patients underwent MR imaging with a 1.5 T scanner system, including diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and 800 s/mm2). The entire tumor volume was manually delineated on the ADC maps, using the T2-weighted images and DWIs with b = 800 s/mm2 as a guide to the lesion location. The Mann-Whitney rank-sum test for independent samples was performed to compare the histogram parameters of patients with lymphoma and SCC. RESULTS: The SCCs showed significantly higher median ADC (ADCmedian) and mean ADC (ADCmean) values, compared to lymphomas (p < 0.001), while they exhibited lower kurtosis and skewness without reaching significance (p = 0.066 and 0.148, respectively). The ADCmean and ADCmedian had the best discriminative powers for differentiating lymphoma and SCC, with an area under the curve of 87% and 85%, respectively. The optimal cutoff values for ADCmean and ADCmedian as predictors for lymphoma were ≤ 0.83 × 10-3 mm2/s and ≤ 0.73 × 10-3 mm2/s, respectively. CONCLUSIONS: The whole-lesion ADC histogram analysis of cervical lymphadenopathy may help to discriminate lymphomas from non-nasopharyngeal SCC in patients with unknown clinical primary tumor.

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence.

Head and neck squamous cell carcinoma is typically characterized by a high incidence of local recurrences. It has been extensively shown that mucosa from head and neck squamous cell carcinoma patients carries both genetic and gene expression alterations, which are mostly attributable to major etiologic agents of head and neck squamous cell carcinoma. We previously identified a signature of microRNAs (miRNAs) whose high expression in tumors is predictive of recurrence. Here, we investigated whether the deregulation of miRNA expression in the tumor-surrounding mucosa is correlated to disease recurrence. Specifically, comparing the miRNA expression in matched tumoral, peritumoral, and normal tissues collected from head and neck squamous cell carcinoma patients, we identified 35 miRNAs that are deregulated in both tumoral and peritumoral tissues as compared with normal matched samples. Four of these composed a miRNA signature that predicts head and neck squamous cell carcinoma local recurrence independently from prognostic clinical variables. The predictive power of the miRNA signature increased when using the expression levels derived from both the peritumoral and the tumoral tissues. The expression signal of the miRNAs composing the predictive signature correlated with the transcriptional levels of genes mostly associated with proliferation. Our results show that expression of miRNAs in tumor-surrounding mucosa may strongly contribute to the identification of head and neck squamous cell carcinoma patients at high risk of local recurrence.

Cytology and human papillomavirus testing on cytobrushing samples from patients with head and neck squamous cell carcinoma.

BACKGROUND: The increasing incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) highlights the need for simple and effective tools to evaluate head and neck lesions and their HPV status. The main objective of the current study was to investigate the association between abnormal cytology and HPV infection, assessed on cytobrushing samples, and histologically confirmed HNSCC. Second, the authors attempted to investigate whether HPV status on cytobrushing samples reflected that of the tumoral tissue. METHODS: A total of 164 samples from HNSCC, nonmalignant lesions, or healthy mucosae of the oral cavity and oropharynx were collected by cytobrushing in PreservCyt solution and evaluated by liquid-based cytology and Linear Array HPV genotyping test. All the findings from the cytologic samples were compared with those from the corresponding histologic samples. RESULTS: Patients with abnormal cytology had a significantly higher risk of having an HNSCC (odds ratio [OR], 9.18; 95% confidence inteval [95% CI], 3.27-26.49). The association was stronger for oral cancer (OR, 10.86; 95% CI, 2.51-51.06) than oropharyngeal cancer (OR, 8.45; 95% CI, 1.62-49.82). HPV positivity in the oropharyngeal cytobrushing was associated with a nearly 5-fold higher risk of having abnormal cytology (OR, 4.57; 95% CI, 1.57-13.57) as well as histologically proven oropharyngeal cancer (OR, 5.09; 95% CI, 1.09-31.61). Comparing the HPV status on cytologic and corresponding histologic samples from patients with HNSCC, we found that 90.4% of the cases were concordant (kappa, 0.796). CONCLUSIONS: Abnormal brushing cytology is strongly associated with a diagnosis of HNSCC, whereas HPV positivity on cytobrushing samples is only associated with oropharyngeal cancer. HPV testing on cytobrushing samples represents a valid option for the assessment of HPV infection in patients with oropharyngeal cancer.

A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx.

BACKGROUND: The purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer. METHODS: All consecutive patients with biopsy-proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. A retrospective review of medical records including surgical, pathological and follow-up reports was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group. RESULTS: The study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis. CONCLUSIONS: Our study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC.

Combined TP53 status in tumor-free resection margins and circulating microRNA profiling predicts the risk of locoregional recurrence in head and neck cancer.

Locoregional recurrences represent a frequently unexpected problem in head and neck squamous cell carcinoma (HNSCC). Relapse often (10-30%) occurs in patients with histologically negative resection margins (RMs), probably due to residual tumor cells or hidden pre-cancerous lesions in normal mucosa, both missed by histopathological examination. Therefore, definition of a 'clean' or tumor-negative RM is controversial, demanding for novel approaches to be accurately explored. Here, we evaluated next generation sequencing (NGS) and digital PCR (dPCR) as tools to profile TP53 mutational status and circulating microRNA expression aiming at scoring the locoregional risk of recurrence by means of molecular analyses. Serial monitoring of these biomarkers allowed identifying patients at high risk, laying the ground for accurate tracking of disease evolution and potential intensification of post-operative treatments. Additionally, our pipeline demonstrated its applicability into the clinical routine, being cost-effective and feasible in terms of patient sampling, holding promise to accurately (re)-stage RMs in the era of precision medicine.

Extraneural Sclerosing Perineurioma of the Tongue.

Perineurioma (PN) is an uncommon benign peripheral nerve sheath tumor. For the rarity of this tumor in the oral cavity, otolaryngologists and oral surgeons might not be familiar with this entity. Perineuriomas are typically benign and complete excision is deemed adequate management. Thus, their histological recognition is mandatory to avoid unnecessary overtreatment. We report the clinicopathologic findings of an uncommon variant, the Extraneural Sclerosing PN, in an unusual and never described site, the tongue.

Magnetic resonance imaging-based prediction models for tumor stage and cervical lymph node metastasis of tongue squamous cell carcinoma.

Purpose: To evaluate the ability of preoperative MRI-based measurements to predict the pathological T (pT) stage and cervical lymph node metastasis (CLNM) via machine learning (ML)-driven models trained in oral tongue squamous cell carcinoma (OTSCC). Materials and methods: 108 patients with a new diagnosis of OTSCC were enrolled. The preoperative MRI study included post-contrast high-resolution T1-weighted images acquired in all patients. MRI-based depth of invasion (DOI) and tumor dimension-together with shape-based and intensity-based features-were extracted from the lesion volume segmentation. The entire dataset was randomly divided into a training set and a validation set, and the performances of different types of ML algorithms were evaluated and compared. Results: MRI-based DOI and tumor dimension together with several shape-based and intensity-based signatures significantly discriminated the pT stage and LN status. The overall accuracy of the model for predicting the pT stage was 0.86 (95%CI, 0.78-0.92) and 0.81 (0.64-0.91) in the training and validation sets, respectively. There was no improvement in the model performance upon including shape-based and intensity-based features. The model for predicting CLNM based on DOI and tumor dimensions had a fair accuracy of 0.68 (0.57-0.78) and 0.69 (0.51-0.84) in the training and validation sets, respectively. The shape-based and intensity-based signatures have shown potential for improving the model sensitivity, with a comparable accuracy. Conclusion: MRI-based models driven by ML algorithms could stratify patients with OTSCC according to the pT stages. They had a moderate ability to predict cervical lymph node metastasis.

A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

A mesenchymal chondrosarcoma with aberrant nuclear expression of STAT6: a potential diagnostic pitfall.

STAT6 is usually considered to be a very sensitive and specific immunomarker for diagnosis of solitary fibrous tumor (SFT), being a surrogate of the NAB2-STAT6 fusion gene identified in most cases of this tumor. STAT6 expression has also been reported in rare cases of other soft tissue tumors, such as low-grade fibromyxoid sarcoma, myxoid/round cell liposarcoma, dedifferentiated liposarcoma and deep fibrous histiocytoma. The aim of this study was to report, for the first time, a case of mesenchymal chondrosarcoma showing diffuse aberrant immunohistochemical expression of STAT6. Molecular biology, showing the HEY1-NCOA2 fusion gene, was crucial to rule out SFT.

Sporadic diffuse neurofibroma of the retropharyngeal space.

Neurofibroma (NF) rarely arises in the retropharyngeal space (RPS) of patients with or without Neurofibromatosis type I (NF-I). The diffuse subtype of NF (DNF) is characterized by an infiltrative growth pattern and typically involves the skin and subcutaneous tissue of the head and neck. We describe the clinic-pathologic features of a DNF involving the RPS of an adult without NF-I. To date, this subtype of NF has never been reported at this site.