Undifferentiated Malignant Tumor Research Articles

Oral T-cell-rich large B-cell lymphoma in a horse.

Lymphoma is the most common tumor of hematopoietic origin in horses. The course of the disease and clinical signs vary greatly, depending on tumor location and extent. The aim of this report is to describe the occurrence of T-cell-rich oral large B-cell lymphoma with marked local infiltration in a 25-year-old Crioula mare. The mare showed an increase in volume on the right side of its face, dyspnea, anorexia, and progressive weight loss. The clinical assessment showed that the lesion was located in the rostral and caudal sinuses and was markedly invasive to adjacent structures. The autopsy revealed a yellow mass with a soft to firm consistency, infiltrating multiple bones in the skull, and extensively invading the hard palate and masseter muscle. Histologically the mass comprised an undifferentiated malignant neoplasm characterized by a densely cellular neoplasm composed of large CD20 + neoplastic B-lymphocytes admixed with sheets of small, CD3 + reactive T-lymphocytes supported by delicate fibrovascular stroma leading to the diagnosis of oral T-cell-rich large B-cell lymphoma.

CIC-DUX4 Sarcoma Involving the Skull Base: A Rare Presentation and Review of the Literature.

Background CIC-DUX4 sarcoma is a rare, aggressive tumor that is difficult to diagnose. Although it is closely related to Ewing's sarcoma, each is a distinct pathologic entity and both have been previously reported in the skin, lymph nodes, and viscera. We report the first description of CIC-DUX4 involving the posterior cranial fossa and review the distinctive symptomatology, morphology, immunoprofile, and genetic signature that differentiate this rare tumor. Case Report A 32-year-old man presented with an enlarging right lateral neck mass, progressive hoarseness, and orofacial pain. Biopsy revealed a high-grade undifferentiated malignant neoplasm. Imaging demonstrated an 8-cm mass in the right neck extending to the skull base and abutting the carotid sheath, in addition to pulmonary nodules and pelvic lymphadenopathy. Despite initial response to chemotherapy, he experienced disease progression and underwent surgical resection, radical neck dissection, and brachytherapy. Definitive pathologic diagnosis was achieved with next-generation sequencing. Within weeks of treatment, he developed symptoms reflecting progression of disease involving the neck, posterior cranial fossa, and lung. Adjuvant chemotherapy was planned, but the patient succumbed to his disease prior to initiation of further therapy. Conclusion CIC-DUX4 sarcomas are uncommon and can progress rapidly. Diagnosis requires either fluorescence in situ hybridization or next-generation sequencing. Due to its rarity, there is no standard-of-care treatment for this tumor and further investigations are needed to understand disease behavior and develop targeted therapeutic modalities.

Malignant Undifferentiated and Rhabdoid Tumors of the Gastroesophageal Junction and Esophagus with SMARCA4 Loss: A Case Series.

Undifferentiated SMARCA-4 deficient carcinoma of the esophagus and gastroesophageal junction is a rare, highly aggressive and diagnostically challenging malignancy. Here we present a case series of high-grade undifferentiated malignant neoplasms of the esophagus and gastroesophageal junction that share SMARCA4 loss by immunohistochemistry and demonstrate a rhabdoid phenotype. Five cases are presented, including 4 men and 1 woman with an age range of 48-79 years. Interestingly, only one case showed intestinal metaplasia (Barrett esophagus) and no cases demonstrated glandular dysplasia or glandular differentiation. In all, the lesional cells were immunoreactive with antibodies to keratins (3/5), CD34 (2/4), and CD138 (4/5). SMARCA4 expression was diffusely lost in all cases whereas SMARCB1 expression was intact. OncoScanTM assay demonstrated loss of SMARCA4 in all cases analyzed. Additional OncoScanTM findings included abnormalities of CDKN2A in 2/3 cases, abnormalities of TP53 in 2/3 cases, and abnormalities of PTPRD in 2/3 cases, among other abnormalities.

Undifferentiated and Dedifferentiated Metastatic Melanomas Masquerading as Soft Tissue Sarcomas: Mutational Signature Analysis and Immunotherapy Response

The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.

Establishment of predictive nomogram and web-based survival risk calculator for desmoplastic small round cell tumor: A propensity score-adjusted, population-based study.

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study's objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan-Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9-28.1) months and 27 (interquartile range 23.6-30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy.

Establishment of predictive nomogram and web-based survival risk calculator for desmoplastic small round cell tumor: A propensity score-adjusted, population-based study.

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study's objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan-Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9-28.1) months and 27 (interquartile range 23.6-30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times: 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy.

A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.

Neuroblastoma has obvious heterogeneity. It is one of the few undifferentiated malignant tumors that can spontaneously degenerate into completely benign tumors. However, for its high-risk type, even with various intensive treatment options, the prognosis is still unsatisfactory. At the same time, a large number of research data show that the abnormal amplification and high-level expression of the MYCN gene are positively correlated with the malignant progression, poor prognosis, and mortality of neuroblastoma. In this context, this article explores the role of the N-Myc, MYCN gene expression product on its target genes related to the cell cycle and reveals its regulatory network in promoting tumor proliferation and malignant progression. We hope it can provide ideas and direction for the research and development of drugs targeting N-Myc and its downstream target genes.

Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity.

Among mesenchymal tumors, MAML2 gene rearrangements have been described in a subset of composite hemangioendothelioma and myxoinflammatory fibroblastic sarcoma (MIFS). However, we have recently encountered MAML2-related fusions in a group of seven undifferentiated malignant epithelioid neoplasms that do not fit well to any established pathologic entities. The patients included five males and two female, aged 41-71 years old (median 65 years). The tumors involved the deep soft tissue of extremities (hip, knee, arm, hand), abdominal wall, and the retroperitoneum. Microscopically, the tumors consisted of solid sheets of atypical epithelioid to histiocytoid cells with abundant cytoplasm. Prominent mitotic activity and necrosis were present in 4 cases. In 3 cases, the cells displayed hyperchromatic nuclei or conspicuous macronucleoli, and were admixed with background histiocytoid cells and a lymphoplasmacytic infiltrate. By immunohistochemistry (IHC), the neoplastic cells had a nonspecific phenotype. On targeted RNA sequencing, MAML2 was the 3' partner and fused to YAP1 (4 cases), ARHGAP42 (2 cases), and ENDOD1 (1 case). Two cases with YAP1::MAML2 harbored concurrent RAF kinase fusions (RBMS3::RAF1 and AGK::BRAF, respectively). In 2 cases with targeted DNA sequencing, mutations in TP53, RB1 and PTEN were detected in 1 case, and PDGFRB mutations, CCNE1 amplifications and CDKN2A/2B deletion were detected in another case, which showed strong and diffuse PDGFRB expression by IHC. Of the 4 cases with detailed clinical history (median follow-up period 8months), three developed distant metastatic disease (one of which died of disease); one case remained free of disease 3 years following surgical excision. In conclusion, we describe a heterogeneous series of MAML2-rearranged undifferentiated malignant epithelioid neoplasms, a subset of which may overlap with a recently described MIFS variant with YAP1::MAML2 fusions, further expanding the clinicopathologic spectrum of mesenchymal neoplasms with recurrent MAML2 gene rearrangements.

Lymphoepithelial like carcinoma of the anorectal junction, a rare entity associated with human papillomavirus rather than Epstein-Barr virus: a case report

The anal canal is a rare site for lymphoepithelial-like carcinoma (LELC) and has only been reported in two patients. LELC is an undifferentiated malignant neoplasm with lymphoid background that has been reported at various sites like salivary glands, breast etc. however very few cases have been reported in gastrointestinal (GI) tract. We report the third case of a 58-year-old female who presented with a complaint of mild constipation and rectal pressure for eight months. Endoscopic ultrasound (EUS) showed a 0.8 cm nodule at the anorectal junction which was resected. Pathology showed LELC of the anorectal junction with diffuse positivity with p16 immunostaining. Polymerase chain reaction (PCR) for human papillomavirus (HPV) was positive for high-risk HPV-16, in situ hybridization (ISH) for Epstein-Barr virus (EBV)-encoded ribonucleic acid (EBER) was negative, and there was no loss of nuclear expression of mismatch repair (MMR) proteins. Patient subsequently received chemoradiation with no evidence of residual disease on restaging scans. The association between LELC of anal canal and viral agents such as HPV or EBV has yet to be established; however, all three cases reported to date, including our current case, were positive for high-risk HPV-16, suggesting a possible role of HPV in tumorigenesis of LELC of the anal canal.

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm: first two cases with clinicopathologic and molecular comparison to eight visceral counterparts

SMARCA4-deficient undifferentiated malignant neoplasms (SD-UMN) comprise a group of aggressive tumors with epithelioid morphology that are characterized by loss of function of SMARCA4, a component of the SWI/SNF chromatin remodeling complex. SD-UMN was first recognized in the thoracic cavity but is now appreciated to occur at multiple anatomic sites. A notable exception has been skin. Here we report the first two cases of primary cutaneous SD-UMN and compare their features to a cohort of eight visceral cases arising in lung, gastrointestinal tract, and gallbladder. Evidence for a bona fide cutaneous origin included extensive clinical, radiologic, and serologic analyses that failed to identify a metastatic source as well as the molecular identification of a UV-associated mutational pattern. The cutaneous cases showed strikingly similar morphologic, immunohistochemical, and molecular features to the visceral cases, strongly suggesting that they belong to this family of tumors. In addition to biallelic inactivation of SMARCA4, both cutaneous tumors also showed biallelic inactivation of TP53 and CDKN2A, findings which also appear common in visceral cases. One patient died of disease at 18 months after diagnosis, consistent with the aggressive nature of this tumor. Our results expand the anatomic spectrum of SD-UMN, adding this entity to an already challenging differential diagnosis that includes melanoma, squamous cell carcinoma, Merkel cell carcinoma, epithelioid sarcoma, and others. Given the potentially aggressive nature of SD-UMN, the timely and accurate diagnosis of this entity may have implications for prognosis and therapy.

PSAT023 Not Every Pain Is a Gain! A Rare Case of Adrenal Leiomyosarcoma.

Abstract Introduction Adrenal leiomyosarcoma (AL) is a rare malignant tumor, representing only 0.1% to 0.2% of all retroperitoneal soft tissue sarcomas in adults (1). A young male's acute abdominal and back pain led to an unusual diagnosis of AL. Case Presentation A 38-year-old male patient with no past medical history presented with a history of right sided abdominal pain of several months duration radiating to the back and significant weight loss. His vital signs were stable; however, he appeared mildly distressed and had tenderness on deep palpation in the right mid-upper quadrant. An abdominal sonogram showed a hypoechoic mass between the liver and the right kidney with no evidence of acute cholecystitis. A CT scan of the abdomen with IV contrast showed a lobulated mass invading the right adrenal gland, measuring 5.4×4.3×5.1 cm, with a post-contrast density measurement of 30 Hounsfield units. Laboratory tests showed plasma renin of 1.8 (upper limit of normal ULN 4.3 ng/ml/h), aldosterone of 8.6 (ULN 21 ng/dl), plasma metanephrine of &amp;lt;0.2 (ULN 0.50 nmol/l), and plasma normetanephrine of 0.49 (ULN 0.90 nmol/l). Additionally, his cortisol level after dexamethasone suppression was 0.9 (ULN 22.4 ug/dl). He underwent a right-sided laparoscopic adrenalectomy. The histopathological testing returned as a high-grade undifferentiated malignant neoplasm consistent with leiomyosarcoma. The IHC stains showed positive staining for SMA, CD10, and GATA3. He underwent whole-body PET/CT that showed multiple hypermetabolic abnormalities, including the right adrenalectomy bed, with a possible tumor invading the right upper renal pole. Systemic chemotherapy with doxorubicin and dacarbazine was initiated. Foundation panel testing showed NF1 loss on exons 2-3, CDKN2A/B CDKN2A rearrangement on exon 2, and TP53 loss on exons 1-4. He has received two rounds of chemotherapy, with no evidence of disease progression. Discussion Adrenal leiomyosarcoma usually originates from the smooth muscle cells of the adrenal or adjacent vascular structures. The tumor is asymptomatic until it enlarges and compresses the surrounding structures. Currently, there are about 50 reported valid cases (2) with no reports of NF-1 exon loss to our knowledge. The primary treatment is radical surgery with or without adjuvant chemotherapy and radiotherapy. Foundation panel testing showing NF-1 and TP53 exon loss may guide future targeted therapy. References 1-Fatema Jabarkhel, Henri Puttonen, Lina Hansson, Andreas Muth, Oskar Ragnarsson, Primary Adrenal Leiomyosarcoma: Clinical, Radiological, and Histopathological Characteristics, Journal of the Endocrine Society, Volume 4, Issue 6, June 2020. 2-Bahador Oshidari, Amir Zamani, Hooman Bahrami-Motlagh, Elena Jamali, Setareh Mahmoodi, Manoochehr Ebrahimian, Primary leiomyosarcoma of the adrenal; a case report, International Journal of Surgery Case Reports, Volume 90, 2022, 106707. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Abstract #1141458: Undifferentiated Malignant Neoplasm of the Thyroid with Spindle Cells in a Patient with a Rapidly Enlarging Neck Mass and Pulmonary Nodules

Spindle cell neoplasms (SCNs) of the thyroid are rare, and can be classified into benign and malignant lesions. Benign SCNs are described as isolated tumors within the thyroid parenchyma that are composed of spindle-shaped cells. Medullary and anaplastic carcinoma of the thyroid are among the most well-established malignancies of the thyroid with spindle cell features.

Lymphoepithelial carcinoma of the oral mucosa. A rare histopathologic subtype of squamous cell carcinoma

<h3>Objectives</h3> Lymphoepithelial carcinoma (LEC) represents a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with non-keratinizing undifferentiated nasopharyngeal carcinoma (NPC). LEC may be etiologically associated with EBV, especially in endemic regions. Although being described in several locations of the head and neck, the oral mucosa seems to be an infrequent site of involvement. Herein, we present a case of an EBV-negative oral LEC and discuss the diagnostic challenges. <h3>Findings</h3> A 51 year-old male Filipino patient suffering from chronic kidney disease presented for the evaluation of a swelling in the right mandible, first noticed by the patient a few days ago. Clinically, the right posterior mandibular gingiva appeared enlarged and hemorrhagic, covered by ulcerated mucosa, while the adjacent teeth displayed high mobility. Extraorally, a painful and slightly movable lymph node in the right submandibular area was palpated. Radiographic evaluation revealed extensive bone loss in the right posterior mandible. With a provisional diagnosis of lymphoma or SCC, an incisional biopsy was performed. Histopathologic examination revealed invasion of the underlying connective tissue by pleomorphic cells of epithelioid morphology, occasionally arranged in syncytial islands, arising from a partially ulcerated, non-keratinized squamous epithelium. A prominent diffuse lymphocytic cell infiltrate surrounding the tumor cells was also detected. The neoplastic cells expressed pancytokeratin, CK5/6, p63, and p40, while p16, LMP-1, and in situ hybridization for EBV RNA were negative. A final diagnosis of moderately to poorly differentiated SCC with features indicative of LEC was rendered and the patient was referred for further management. <h3>Conclusions</h3> LEC should be considered in the differential diagnosis of undifferentiated malignant neoplasms displaying close association with diffuse lymphoid aggregates. The evaluation of nasopharynx is justified to rule out metastatic NPC, as the separation of these two entities microscopically is not feasible.

The role of PET-CT with 18F-FDG in initial assessment of patients with carcinoma of unknown primary (CUP) in the head and neck

Introduction. Cancer metastases from an unknown primary origin (CUP) in the head and neck area include a large heterogeneous group of tumor formations, the primary localization of which could not be established even after a thorough diagnostic search. Combined positron emission computed tomography (PET-CT) with 18F-FDG has a high level of detection of primary neoplasms as a result of simultaneous acquisition of precisely combined anatomical and functional images of the entire body.Objectives. 1. To evaluate the possibility of using PET-CT (positron emission tomography in combination with computed tomography) with 18F-FDG (18-fluorodeoxyglucose) in patients with metastases from the CUP (carcinoma unknown primary) in the head and neck.2. To determine the effectiveness of PET-CT for the detection of primary tumor focus in patients with histologically verified diagnosis of CUP in the head and neck.3. To evaluate the contribution of the PET-CT technique in assessing the prevalence of the disease in patients diagnosed with head and neck cancer.Materials and methods. 134 patients diagnosed with CUP in the head and neck from September 2018 to March 2019 were included to this retrospective study: 35(26.1%) women and 99(73.9%) men, with the mean age of 61.9 ± 7.5 years. All patients underwent a biopsy from at least one metastatic lesion, and the malignant nature of the neoplasm was histologically verified. Before PET-CT with 18F-FDG, standard oncological evaluation was carried out to detect primary tumor.Results. Among 134 patients comprised the study, initial histological diagnoses were: squamous cell cancer (n = 82, 61.2%), melanoma (n = 5, 3.7%), undifferentiated carcinoma (n = 20, 15%), adenocarcinoma (n = 21, 15.6%) and undifferentiated malignant neoplasm (n = 6, 4.5%).With PET-CT with 18F-FDG, primary tumor location was revealed in 72 (54%) of the patients. New metastatic lesions were found in 60 (44.7%) of the patients.Change in the TNM stage was observed in 95(71%) of all cases after PET-CT with 18F-FDG. It was associated both with the detection of the primary tumor and the identification of new metastatic foci.Conclusions. Use of PET-CT with 18F-FDG allows to carry out oncological evaluation more precisely than the standard procedures in the majority of patients with CUP in the head and neck region. In a significant quota of cases, this method is in a position also to help to identify the primary tumor lesion, which, in turn, influences on strategy of treatment and also on the prognosis of disease. PET-CT with 18F-FDG should be included to the protocol of radiological examination in patients with CUP in the head and neck anatomic area.

The role of PET-CT with &lt;sup&gt;18&lt;/sup&gt;F-FDG in initial assessment of patients with carcinoma of unknown primary (CUP) in the head and neck

Introduction. Cancer metastases from an unknown primary origin (CUP) in the head and neck area include a large heterogeneous group of tumor formations, the primary localization of which could not be established even after a thorough diagnostic search. Combined positron emission computed tomography (PET-CT) with 18 F-FDG has a high level of detection of primary neoplasms as a result of simultaneous acquisition of precisely combined anatomical and functional images of the entire body. Objectives. 1. To evaluate the possibility of using PET-CT (positron emission tomography in combination with computed tomography) with 18 F-FDG (18-fluorodeoxyglucose) in patients with metastases from the CUP (carcinoma unknown primary) in the head and neck. To determine the effectiveness of PET-CT for the detection of primary tumor focus in patients with histologically verified diagnosis of CUP in the head and neck. To evaluate the contribution of the PET-CT technique in assessing the prevalence of the disease in patients diagnosed with head and neck cancer. Materials and methods. 134 patients diagnosed with CUP in the head and neck from September 2018 to March 2019 were included to this retrospective study: 35(26.1%) women and 99(73.9%) men, with the mean age of 61.9 ± 7.5 years. All patients underwent a biopsy from at least one metastatic lesion, and the malignant nature of the neoplasm was histologically verified. Before PET-CT with 18F-FDG, standard oncological evaluation was carried out to detect primary tumor. Results. Among 134 patients comprised the study, initial histological diagnoses were: squamous cell cancer (n = 82, 61.2%), melanoma (n = 5, 3.7%), undifferentiated carcinoma (n = 20, 15%), adenocarcinoma (n = 21, 15.6%) and undifferentiated malignant neoplasm (n = 6, 4.5%). With PET-CT with 18F-FDG, primary tumor location was revealed in 72 (54%) of the patients. New metastatic lesions were found in 60 (44.7%) of the patients. Change in the TNM stage was observed in 95(71%) of all cases after PET-CT with 18 F-FDG. It was associated both with the detection of the primary tumor and the identification of new metastatic foci. Conclusions. Use of PET-CT with 18 F-FDG allows to carry out oncological evaluation more precisely than the standard procedures in the majority of patients with CUP in the head and neck region. In a significant quota of cases, this method is in a position also to help to identify the primary tumor lesion, which, in turn, influences on strategy of treatment and also on the prognosis of disease. PET-CT with 18 F-FDG should be included to the protocol of radiological examination in patients with CUP in the head and neck anatomic area.

Primary soft palate biphasic synovial sarcoma - case report and literature review

Abstract BACKGROUND. Synovial sarcomas of the soft tissue are a particular type of sarcomas that rarely appear in the head and neck region. CASE REPORT AND COMMENTS. We present the case of a 27-year-old patient diagnosed in 2017 with soft palate biphasic synovial sarcoma who presented with recurrent microepistaxis, nasal obstruction, left cephalalgia and aural fullness in the left ear. The clinical examination showed a tumor with approximately 4/6 cm in diameter, covered with sero-sanguinolent secretions, pulsating in nature, completely obstructing the left choana. The surgical treatment consisted of complete removal of the tumor under endoscopic guidance with electrocauterization of the insertion area, without further postoperative radiotherapy. The histopathological aspect was suggestive for pleomorphic sarcoma, poorly differentiated, confirming the local recurrence of the tumor. The patient also presented lung metastasis from undifferentiated malignant tumor. CONCLUSION. The particularity of this case is represented by the extremely rare occurrence of synovial sarcoma in the head and neck region, especially at the level of the soft palate. Complete resection of the tumor with negative margins represent the mainstay of treatment, associated with adjuvant radiotherapy, with an important role in improving disease-specific survival.

HYPEREOSINOPHILIA, MYELOPHITISIS AND CUTANEOUS METASTASES: ATYPICAL PRESENTATION OF NON-SMALL CELL LUNG CARCINOMA

Hypereosinophilia is defined as an eosinophil count greater than 1.500 cells/mm. It is usually associated with organ dysfunction due to visceral eosinophilic infiltration or tissue damage mediated by eosinophilopoietic cytokines, like IL-5. Determining its etiology represents a diagnostic challenge, as numerous conditions are associated with its occurrence, especially parasitic diseases, allergic disorders, medications and neoplasms. Paraneoplastic eosinophilia usually develops in the context of tumors of the lower gastrointestinal tract, lung, Hodgkin's lymphoma, peripheral T-cell lymphomas (PTCL), and its pathophysiology is associated with interleukin-5 (IL-5) secretion, an eosinophil proliferation-inducing cytokine. To describe a clinical case of paraneoplastic hypereosinophiliadue to lung cancer, a rare laboratory manifestation, in a case with an advanced stage of the disease and catastrophic evolution. A 68-year-old woman, with a history of obesity and SAH, presents to the health service of the HC/FMUSP due to adynamia, dyspnea on exertion and perception of multiple violaceous cutaneous nodules on the scalp, thorax, abdomen and extremities, 45 days long. On physical examination, she had cutaneous-mucosal pallor, poor general condition, hypoxemia, and disseminated cutaneous nodules of up to 5 cm. Blood count revealed: Hb 8.9 g/d, Ht 26%, MCV 89 fl, 75.980 leukocytes/mm 3 (31.920 neutrophils with left shift to promyelocytes/ 40.270 eosinophils/ 0 basophils/ 2.280 lymphocytes/ 1.520 monocytes) and 107.000 platelets/mm 3 ; LDH = 592 U/L (NSV up to 214 U/L); IgE = 496 IU/mL (NSV up to 100 IU/mL). Myelogram showed hypercellular bone marrow with massive infiltration by elements of non-hematopoietic origin, as well as prominent medullary eosinophilia. Computed tomography (CT) showed an irregular lung mass, 5 cm in diameter, in the right upper lobe, suggestive of a primary neoplastic site, as well as secondary implants in the liver parenchyma, adrenal glands and subcutaneous cellular tissue/skin. Biopsy of subcutaneous nodules showed undifferentiated malignant neoplasm of epithelioid pattern, with immunohistochemistry: AE1/AE3 positive, 34BE12 positive, MELAN-1 negative, HMB45 negative, S100 negative, p63 negative, characterizing squamous cell carcinoma. During hospitalization, the patient rapidly evolved with tumor lisis syndrome, acute renal failure and fulminant liver failure, and died after a short period of hospitalization. We report an atypical case of pulmonary squamous cell carcinoma, marked by paraneoplastic eosinophilia, bone marrow infiltration, cutaneous metastasis, spontaneous tumor lysissyndrome and acute liver failure. Paraneoplastic hyperosinophilia is a marker associated withpoor prognosis in solid tumors, usually reflecting an elevated tumor mass, with multi-metastatic disease, as presented in our case. Although it is a rare condition, paraneoplastic eosinophilia mustfall within the differential scope of causes of sustained elevation of eosinophils. Rapid recognition and prompt treatment of the underlying neoplasm may provide a more favorable evolution.

Assessment of Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Carcinoma of Unknown Primary

Objectives: to assess the possibility of using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with carcinoma of unknown primary (CUP); to determine the effectiveness of PET/CT for detecting a primary tumor lesion in patients with a histologically verified diagnosis of CUP and the contribution of PET/CT procedure to the process of disease staging in these patients.Material and methods. From September 2018 to March 2019, the retrospective study included a total of 187 patients (64 (34.2%) females and 123 (65.8%) males) diagnosed with CUP. The patients’ mean age was 61.9 ± 7.5 years. Before PET/CT, all the patients underwent puncture biopsy of at least one metastatic lesion, which histologically verified the malignant nature of the neoplasm. A number of conventional studies were also performed as part of an oncosearch to identify the nature of a primary cancer lesion.Results. Biopsy of lymph node metastases in 187 patients included in the study showed the following distribution according to the histological types of the tumor: 87 (46.5%) patients were diagnosed with squamous cell carcinoma, 15 (8%) with melanoma, 45 (24.1%) with undifferentiated carcinoma, 23 (12.3%) with adenocarcinoma, 17 (9.1%) with undifferentiated malignant neoplasm. The examination could identify a primary tumor site in 93 (49.7%) patients; no primary source was found in 94 (50.3%) patients. After PET/CT, there were no significant differences in the age of patients with and without CUP. PET/CT revealed new, previously undetected metastatic lesions in 93 cases, accounting for 49.7% of the entire sample. It is worth noting that after PET/CT, a change in the stage of tumor development tool place in 131 (70.1%) cases, which was associated with both the detection of the primary tumor and the identification of new metastatic lesions. The stage change was significantly more frequently observed in patients with detected CUP than in those with undetected CUP (100% vs. 40.4%; p &lt; 0.001).Conclusion. PET/CT can more accurately determine the stage of cancer in a large proportion of patients with CUP. The technique is able to identify the primary tumor in a significant number of cases, which in turn affects treatment policy and prognosis in these patients. The use of PET/CT should be obligatorily included in the examination protocol for patients with CUP.

ERG Immunoreactivity in Blastic Hematolymphoid Neoplasms: Diagnostic Pitfall in the Workup of Undifferentiated Malignant Neoplasms.

Undifferentiated malignant neoplasms pose diagnostic challenges, and reliable immunohistochemical markers with well-characterized staining profiles are desirable when characterizing them. Our initial observation of erythroblast transformation specific regulated gene-1 (ERG) reactivity in myeloid sarcomas led us to broadly explore the utility of ERG as a marker of immature hematolymphoid neoplasms presenting in extramedullary sites. We stained 207 immature and mature hematolymphoid lesions as well as 39 benign hematolymphoid tissues and found weak-to-moderate ERG immunopositivity in 15 of 16 (94%) acute myeloid leukemias/myeloid sarcomas, including 4 of 5 (80%) CD34-negative/CD117-negative acute myeloid leukemias/myeloid sarcomas. ERG positivity was also seen in all 9 cases of B-lymphoblastic and T-lymphoblastic leukemia/lymphoma, all 3 cases of hematogone hyperplasia, and all 4 cases of systemic mastocytosis. ERG was negative in 148 mature B-cell and T-cell lymphomas, including 2 high-grade B-cell lymphomas and 2 blastoid variant mantle cell lymphomas; 23 histiocytic/dendritic cell neoplasms; 2 indolent T-lymphoblastic proliferations; and 2 blastic plasmacytoid dendritic cell neoplasms. We conclude that ERG immunoreactivity may pose a significant diagnostic pitfall in the workup of undifferentiated malignant neoplasms, particularly those presenting in extramedullary sites.

Incidence of NUT carcinoma in Western Australia from 1989 to 2014: a review of pediatric and adolescent cases from Perth Children\u2019s Hospital

BackgroundNUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge. In the absence of a clearly determined incidence for NC, we sought to study the diagnosis of patients in a well-defined population.MethodsWe systematically reviewed records of all patients that presented to the Oncology Department of the Princess Margaret Hospital for Children from 1989 to 2014. This institution in the geographically isolated state of Western Australia has a catchment population of around 2 million. We then identified all high grade undifferentiated sarcomas or carcinomas in the 0–16 year age group.ResultsOver 26 years, we found 14 patients of 16 years or younger with undifferentiated malignant tumors. Of these, five tumors were positive by immunohistochemistry for the NUT/NUTM1 (Nuclear Protein in Testis) protein and/or the translocation t(15;19). Three patients presented with thoracic tumors, one with a para-spinal tumor, and one had an upper airway nasopharyngeal carcinoma. In all five cases, there was an initial response to therapy and then progression. This 26-year survey was conducted in a geographically isolated state with a well-defined population, and we determined an estimated incidence of NC of around 0.41 per million child years (0–16 yrs. of age) at risk. From three patients it was feasible to derive cell lines for further genetic analyses and drug screening.ConclusionsFor the first time, the incidence of NC could be determined in a well-defined geographic area. The calculated rate of NC incidence is consistent with a history of under-recognition for this malignancy. These findings indicate that improved diagnostic detection of NC would enable better management and counselling of patients. Our findings emphasize the heterogeneity of NC, and they highlight the need to develop personalised therapy options, and to consider a diagnosis of NC in undifferentiated malignant tumors.