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BACKGROUND: Choristoma is a well-defined benign lesion formed by histologically normal tissue in an unusual location. Diagnosis is confirmed after surgical removal of the mass. To our knowledge, to date there has been only one case of thyroid choristoma described in the literature. PATIENT FINDINGS: A 70-year-old man with a history of non-Hodgkin lymphoma presented with sudden cervical enlargement. Cervical CT scan showed a 47mm hypodense nodule on the right thyroid lobe. Fine-needle aspiration revealed follicular lesion of undetermined significance. During the following weeks there was noticeable thyroid enlargement. Reassessment with thyroid ultrasound showed a 73mm nodule. The patient underwent total thyroidectomy. Histopathological examination revealed a choristoma composed of squamous epithelium lined cysts, smooth muscle, adipose tissue, connective tissue, foci of ossification and extramedullary hematopoiesis. No cytological atypia or tumoral necrosis were found. Thyroid choristomas are an exceedingly rare cause of a thyroid nodule.
ABSTRACT
PURPOSE: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients. METHODS: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre. RESULTS: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively). CONCLUSIONS: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies.
Subject(s)
Iodine Radioisotopes , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Female , Male , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/radiotherapy , Thyroid Cancer, Papillary/pathology , Iodine Radioisotopes/therapeutic use , Middle Aged , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Retrospective Studies , Adult , Aged , Treatment Outcome , Telomerase/genetics , Young Adult , Neoplasm Metastasis , Aged, 80 and overABSTRACT
PURPOSE: A clinicopathological classification has been designed to predict recurrence/progression in patients with pituitary adenomas (PAs). We aimed to study its usefulness in predicting PAs that will have a challenging disease course and may require more often complex multimodal and multiple therapeutic approaches. METHODS: Retrospective analysis of 129 patients with PAs operated in our institution between 2001 and 2020 (84 non-clinically functioning PAs, 32 acromegaly, 9 Cushing's disease, 2 prolactinomas and 2 thyrotropinomas). Grading was based on invasion and proliferation: 1a (non-invasive, non-proliferative; n = 59), 1b (non-invasive, proliferative; n = 17), 2a (invasive, non-proliferative; n = 38), and 2b (invasive, proliferative; n = 15). RESULTS: Of the 129 patients, 68 (52.7%) were females, and the mean age at diagnosis was 53.7 ± 15.4 years. The mean follow-up duration was 93.1 ± 61.8 months. Grade 2b PAs when compared to other grades (2b-2a-1b-1a) had significantly higher rates of persistent tumor remnant within 1-year after operation (93-78-18-30%; p < 0.001), active disease at last follow-up (40-27-12-10%; p = 0.004), re-operation (27-16-0-5%; p = 0.023), irradiation (53-38-12-7%; p < 0.001), multimodal treatment (67-49-18-25%; p = 0.003), multiple treatment (33-27-6-9%; p = 0.017). Patients with grade 2b PAs also required a higher mean number of treatments (2.6-2.1-1.2-1.4; p < 0.001). CONCLUSIONS: This clinicopathological classification appears to be a useful grading system to identify PAs that may be more refractory and more often require complex multimodal and multiple therapeutic approaches. Invasive PAs, especially grade 2b tumors, may be more likely to need complex treatment approach, including radiotherapy, and may display higher rates of active disease at last follow-up, despite receiving higher number of treatments.
Subject(s)
Adenoma , Pituitary Neoplasms , Female , Humans , Adult , Middle Aged , Aged , Male , Pituitary Neoplasms/pathology , Retrospective Studies , Portugal , Pituitary Gland/pathology , Adenoma/pathologyABSTRACT
Sarcomas are rare malignant mesenchymal neoplasms, and the knowledge of tumor biology and genomics is scarce. Chemotherapy is the standard of care in advanced disease, with poor outcomes. Identifying actionable genomic alterations may offer effective salvage therapeutic options when previous lines have failed. Here, we report a retrospective cohort study of sarcoma patients followed at our center and submitted to comprehensive genomic profiling between January 2020 and June 2021. Thirty patients were included, most (96.7%) with reportable genomic alterations. The most common alterations were linked to cell cycle regulation (TP53, CDKN2A/B, and RB1 deletions and CDK4, MDM2, and MYC amplifications). Most patients (96.7%) had microsatellite stability and low tumor mutational burden (≤10 muts/megabase (Mb); median 2 Muts/Mb). Two-thirds of patients had actionable mutations for targeted treatments, including five cases with alterations amenable to targeted therapies with clinical benefit within the patient's tumor type, ten cases with targetable alterations with clinical benefit in other tumor types, and five cases with alterations amenable to targeting with drugs under investigation in a clinical trial setting. A significant proportion of cases in this study had actionable genomic alterations with available targeted drugs. Next-generation sequencing is a feasible option for identifying molecular drivers that can provide therapeutic options for individual patients. Molecular Tumor Boards should be implemented in the clinical practice to discuss genomic findings and inform clinically relevant targeted therapies.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Retrospective Studies , Sarcoma/drug therapy , Sarcoma/genetics , Genetic Profile , GenomicsABSTRACT
Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a "fit for all" principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Biomarkers , Humans , Metabolome , Metabolomics/methods , Sarcoma/diagnosisABSTRACT
Bone sarcomas (BS) are rare mesenchymal tumors usually located in the extremities and pelvis. While surgical resection is the cornerstone of curative treatment, some locally advanced tumors are deemed unresectable and hence not suitable for curative intent. This is often true for pelvic sarcoma due to anatomic complexity and proximity to vital structures, making treatment options for these tumors generally limited and not unanimous, with decisions being made on an individual basis after multidisciplinary discussion. Several studies have been published in recent years focusing on innovative treatment options for patients with locally advanced sarcoma not amenable to local surgery. The present article reviews the evidence regarding the treatment of patients with locally advanced and unresectable pelvic BS, with the goal of providing an overview of treatment options for the main BS histologic subtypes involving this anatomic area and exploring future therapeutic perspectives. The management of unresectable localized pelvic BS represents a major challenge and is hampered by the lack of comprehensive and standardized guidelines. As such, the optimal treatment needs to be individually tailored, weighing a panoply of patient- and tumor-related factors. Despite the bright prospects raised by novel therapeutic approaches, the role of each treatment option in the therapeutic armamentarium of these patients requires solid clinical evidence before becoming fully established.
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The microenvironment of pituitary adenomas (PAs) includes a range of non-tumoral cells, such as immune and stromal cells, as well as cell signaling molecules such as cytokines, chemokines and growth factors, which surround pituitary tumor cells and may modulate tumor initiation, progression, invasion, angiogenesis and other tumorigenic processes. The microenvironment of PAs has been actively investigated over the last years, with several immune and stromal cell populations, as well as different cytokines, chemokines and growth factors being recently characterized in PAs. Moreover, key microenvironment-related genes as well as immune-related molecules and pathways have been investigated, with immune check point regulators emerging as promising targets for immunotherapy. Understanding the microenvironment of PAs will contribute to a deeper knowledge of the complex biology of PAs, as well as will provide developments in terms of diagnosis, clinical management and ultimately treatment of patients with aggressive and/or refractory PAs.
Subject(s)
Adenoma , Pituitary Neoplasms , Adenoma/metabolism , Cell Transformation, Neoplastic , Chemokines , Humans , Immunotherapy , Pituitary Neoplasms/metabolism , Tumor MicroenvironmentABSTRACT
Abstract Biological therapies, including anti-TNF agents, are important in the treatment of various chronic inflammatory diseases, including psoriasis, rheumatoid arthritis or inflammatory bowel disease. The increased use of these drugs translates into an increasing awareness of its adverse effects, which include malignancy. In this paper, we describe the case of a 28-year-old woman who developed a spitzoid melanocytic tumor after starting infliximab therapy for ulcerative colitis. The evidence for causality between anti-TNF and melanocytic proliferations is still sparse; nonetheless, treatment-associated immunosuppression seems to play a key role in this phenomenon. Therefore, a regular follow-up with a rigorous skin examination is essential in these patients. Noninvasive techniques such as dermoscopy or reflectance confocal microscopy are particularly useful diagnostic tools in these circumstances.
Subject(s)
Humans , Female , Adult , Skin Neoplasms/diagnosis , Skin Neoplasms/chemically induced , Skin Neoplasms/drug therapy , Nevus, Epithelioid and Spindle Cell/chemically induced , Tumor Necrosis Factor-alpha , Diagnosis, Differential , Infliximab/adverse effectsABSTRACT
Biological therapies, including anti-TNF agents, are important in the treatment of various chronic inflammatory diseases, including psoriasis, rheumatoid arthritis or inflammatory bowel disease. The increased use of these drugs translates into an increasing awareness of its adverse effects, which include malignancy. In this paper, we describe the case of a 28-year-old woman who developed a spitzoid melanocytic tumor after starting infliximab therapy for ulcerative colitis. The evidence for causality between anti-TNF and melanocytic proliferations is still sparse; nonetheless, treatment-associated immunosuppression seems to play a key role in this phenomenon. Therefore, a regular follow-up with a rigorous skin examination is essential in these patients. Noninvasive techniques such as dermoscopy or reflectance confocal microscopy are particularly useful diagnostic tools in these circumstances.
Subject(s)
Nevus, Epithelioid and Spindle Cell , Skin Neoplasms , Adult , Diagnosis, Differential , Female , Humans , Infliximab/adverse effects , Nevus, Epithelioid and Spindle Cell/chemically induced , Skin Neoplasms/chemically induced , Skin Neoplasms/diagnosis , Skin Neoplasms/drug therapy , Tumor Necrosis Factor-alphaABSTRACT
INTRODUCTION: Schwannomas-Schwann cells-originating tumors-may develop in many locations. However, primary schwannomas arising within lymph nodes are extremely rare, with only a few cases described to this date in the English literature. For the intranodal location, most of the cases are described in the abdominal cavity. In these cases, clinicians may consider and check for familial disorders, such as neurofibromatosis type 2 (NF2) and schwannomatosis also called neurofibromatosis type 3. Schwannomas are benign neoplasms. Histologically, differential diagnosis for spindle-cell lesions in lymph nodes is important and must be done carefully, mainly because they may be attributable to metastatic disease. We report a case of a primary schwannoma arising in a cervical lymph node. BACKGROUND: Primary schwannomas arising within lymph nodes are extremely rare, with only a few cases reported. Since they are benign neoplasms, the differential diagnosis with other intranodal spindle cell lesions, mostly malignant, is important. METHODS: An asymptomatic 69-year-old woman, previously submitted to left hemithyroidectomy for a benign folicular nodule, underwent thyroidectomy totalization following the identification of a large thyroid nodule in routine evaluation. RESULTS: Gross and microscopic examination and ancillary studies were consistent with the diagnosis of intranodal schwannoma. The patient had acquired bilateral hypoacusia. Therefore, type 2 neurofibromatosis was considered and vestibular schwannomas ruled out. CONCLUSION: Herein, we present the second case of a primary schwannoma in a cervical lymph node reported so far. The relevance of the differential diagnosis is highlighted.
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OBJECTIVE: To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). METHODS: We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. RESULTS: Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. CONCLUSION: The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
Subject(s)
Salivary Glands, Minor/immunology , Sjogren's Syndrome/blood , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Tertiary Lymphoid Structures/immunology , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , Case-Control Studies , Female , Humans , Inducible T-Cell Co-Stimulator Protein/immunology , Lymphocyte Count , Male , Middle Aged , Odds Ratio , Programmed Cell Death 1 Receptor/immunology , Prospective Studies , Salivary Glands, Minor/pathology , Sialadenitis/immunology , Sialadenitis/pathology , Sjogren's Syndrome/immunology , Sjogren's Syndrome/pathology , T-Lymphocytes, Helper-Inducer/pathology , T-Lymphocytes, Regulatory/pathology , Tertiary Lymphoid Structures/pathologyABSTRACT
Chronic kidney disease (CKD) commonly evolves with disturbances in mineral and bone metabolism, currently defined as CKD-MBD. Management strategies have progressed over the years, but our knowledge regarding evaluation and treatment is still sparse. Herein, we describe a rare case of a hemodialysis patient with apparently fairly controlled hyperparathyroidism (HPTH), who developed multiple symptomatic brown tumors involving the scull, mandible, vertebrae, pelvis, and metacarpus. Parathyroidectomy allowed complete resolution of the bone lesions preventing disastrous consequences.â©.
Subject(s)
Osteitis Fibrosa Cystica , Renal Insufficiency, Chronic , Adult , Female , Humans , Osteitis Fibrosa Cystica/etiology , Osteitis Fibrosa Cystica/surgery , Parathyroidectomy , Renal Dialysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapyABSTRACT
Solitary bone plasmacytomas are part of a wide range of monoclonal neoplasms that share a common progenitor in the B lymphocyte lineage. In their particular case, a single bone lesion is found, most frequently on the axial skeleton, having evidence of no other osteolytic lesions or systemic involvement. Diagnosis can sometimes prove to be difficult as they are rare tumors, occurring in 3 to 5% (up to 10% in some series) of patients with plasma cell neoplasms, with important considerations regarding the differential diagnosis. We report a case of a solitary bone plasmacytoma, found on the ala of the left ilium of a patient during a routine consult due to hip pain.
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Squash cytology (SC) is a very useful procedure during neurosurgical intraoperative consultation (IOC), and it is especially recommended for the evaluation of soft tumors or tumors that are highly cellular (just the characteristics of pediatric central nervous system [CNS] tumors). The aim of this review is to familiarize pathologists with the range of cytomorphologic appearances that can occur during IOC for pediatric CNS tumors and with the diagnostic dilemmas and pitfalls encountered in this setting. This article is based on the medical literature and the authors' experience with a large series of cases accrued over a 12-year period at 3 institutions. SC is a specially recommended procedure in IOC for pediatric CNS tumors; it reveals the fine cellular details and background features in a manner not seen in corresponding frozen sections. Indeed, a differential diagnosis between histologically look-alike processes can be achieved with more confidence if SC is employed.
Subject(s)
Central Nervous System Neoplasms/diagnosis , Cytodiagnosis/methods , Neurosurgical Procedures , Quality Assurance, Health Care , Referral and Consultation , Child , Humans , Intraoperative PeriodABSTRACT
PURPOSE: To report a rare case of lacrimal gland carcinoma ex pleomorphic adenoma (Ca ex PA) with chronic B-cell lymphocytic leukemia (B-CLL) infiltration in a patient without a previous diagnosis of B-CLL. PATIENT AND METHODS: We report a 66-year-old woman who presented with recent worsening of a long-standing right eye proptosis. Sequential orbital computed tomography imaging was performed over the course of 2 years, and biopsy specimens were analyzed. RESULTS: Initial computed tomography scans revealed a lacrimal gland lesion with stable dimensions for more than 1 year and no malignancy features on incisional biopsy. Subsequently, lesion volume growth and bone erosion were documented on orbital computed tomography. Lateral orbitectomy and lacrimal gland resection were performed. Pathology and immunohistochemistry detected Ca ex PA with B-CLL infiltration. CONCLUSION: This case highlights the importance of persistent investigation of clinically suspicious orbital lesions. To our knowledge, this is the first description of a case of lacrimal gland Ca ex PA with B-CLL infiltration.
Subject(s)
Biopsy, Fine-Needle , Cytodiagnosis , Ganglioneuroma/diagnosis , Adult , Child , Diagnosis, Differential , Female , Ganglion Cysts/pathology , Ganglioneuroblastoma/diagnosis , Ganglioneuroblastoma/pathology , Ganglioneuroma/diagnostic imaging , Ganglioneuroma/pathology , Humans , Radiography , Schwann Cells/pathologyABSTRACT
OBJECTIVE: To study the role of fine needle aspiration cytology (FNAC) in the diagnosis of cutaneous and subcutaneous endometriosis. STUDY DESIGN: We present 7 cases of endometriosis in abdominal wall, inguinal region and perineum diagnosed by FNAC. All cases were confirmed with histologic follow-up. Cytologic and histologic material was prepared using standard methods. RESULTS: The smears were highly cellular, showing a hemorrhagic background with hemosiderin-laden macrophages and sheets of epithelial and stromal cells. Occasionally, these cellular components were closely associated. CONCLUSION: FNAC is useful in the diagnosis of cutaneous and subcutaneous endometriosis, providing a rapid and accurate preoperative diagnosis.