RESUMEN
Spindle cell/sclerosing rhabdomyosarcoma is an infrequent subtype of rhabdomyosarcoma according to the World Health Organization Classification of Soft Tissue and Bone Tumours, which includes a novel category of intraosseous spindle-cell rhabdomyosarcomas (ISCRMS) with EWSR1:: or FUS::TFCP2 fusions. We report a case of ISCRMS with EWSR1::TFCP2 fusion presenting in the femur mimicking osteosarcoma in this unusual primary location. We present an 18-year-old male with relapsed widely metastatic sarcoma, morphologically identical to osteosarcoma responding poorly to chemotherapy, initially presenting in the distal femur. Sections showed a high-grade malignant neoplasm with sheets of epithelioid and spindled cells without obvious rhabdomyoblastic differentiation morphologically containing focal areas resembling new bone/osteoid formation. Molecular sequencing identified t(12;22) EWSR1::TFCP2. The tumor cells were diffusely positive for pancytokeratin, MyoD1, and ALK by retrospective immunohistochemistry. Desmin and SATB2 were focally positive. Myogenin was negative, and INI-1 expression was retained. ISCRMS commonly involves craniofacial and pelvic bones, but rarely originates in long bones, as in this case. Initially, osteosarcoma was the primary diagnostic consideration based on distal long bone location, patient age, and evidence of osteoid formation. Distinction between the two entities may be nearly impossible on morphologic grounds alone, which presents a diagnostic pitfall without molecular or extensive immunoprofiling data.
RESUMEN
BACKGROUND: The 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) divides AUS diagnoses into two major subcategories: atypia of undetermined significance (AUS) nuclear atypia (AUS-N) and other (AUS-O). This study aims to compare the histological outcome and malignant rate of pediatric AUS thyroid nodules classified into AUS-N and AUS-O subcategories. DESIGN: A search of our institutional electronic pathology database for the period from January 2012 to July 2023 was conducted to identify pediatric (<21 years old) thyroid nodules that were interpreted as AUS and subsequently had surgery. Cases were further divided into AUS-N and AUS-O subcategories. Results of follow-up surgical resections were collected. The malignant rate was calculated and compared between AUS-N and AUS-O groups. RESULTS: The study identified 62 thyroid nodules from 58 pediatric patients. Among these nodules, 29 and 33 were subcategorized as AUS-N and AUS-O, respectively. Both groups exhibited a female predominance and displayed a similar nodule size distribution. Histological analysis revealed 15 carcinomas in AUS-N nodules, including 11 cases of classic papillary thyroid carcinoma (PTC) and four cases of follicular type of PTC. In contrast, in the AUS-O group, a total of five carcinomas were documented, including two PTCs and three oncocytic thyroid carcinomas. Notably, the malignant rate of AUS-N nodules (52%) is significantly higher than that of AUS-O nodules (15%) (p = .002). CONCLUSION: In pediatric AUS thyroid nodules, the malignant risk in AUS-N is significantly higher than that in AUS-O. These findings may guide more appropriate clinical triage and/or improve management of pediatric patients with AUS thyroid nodules.
RESUMEN
Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.
Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Humanos , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/genética , Masculino , Adulto , Femenino , Adulto Joven , Adolescente , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Niño , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/genética , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/genética , Neoplasias del Mediastino/mortalidad , Inmunohistoquímica , Cromosomas Humanos Par 12/genética , Anciano , Recurrencia Local de Neoplasia/patología , Progresión de la Enfermedad , Polimorfismo de Nucleótido Simple , Aberraciones Cromosómicas , Predisposición Genética a la Enfermedad , Neoplasias TesticularesRESUMEN
OBJECTIVES: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing. METHODS: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT. RESULTS: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT. CONCLUSIONS: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.
Asunto(s)
Enterocolitis , Enfermedad de Hirschsprung , Niño , Humanos , Lactante , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/diagnóstico , Enfermedad de Hirschsprung/cirugía , Recto/cirugía , Estudios Prospectivos , Fuga Anastomótica , Relevancia Clínica , Inflamación/complicaciones , Enterocolitis/diagnóstico , Enterocolitis/etiología , Biopsia/efectos adversos , Estudios Retrospectivos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiologíaRESUMEN
Large cell calcifying Sertoli cell tumors (LCCSCTs) are rare testicular tumors, representing <1 % of all testicular neoplasms. Almost 40 % of patients with LCCSCTs will present in the context of the inherited tumor predisposition syndrome, the Carney complex. While most LCCSCTs are benign, 10-20 % have malignant behavior. The aim of our study was to analyze LCCSCTs for novel molecular alterations in addition to PRKAR1A mutations and to identify potential drivers for malignant progression. Eight LCCSCTs diagnosed at two institutions were included. Two patients had the Carney complex confirmed on subsequent genetic testing, and two tumors had several adverse pathological findings. One patient presented with metastatic disease at the time of initial diagnosis. Targeted next-generation sequencing detected PRKAR1A alterations in all cases, with heterozygous PRKAR1A mutations in 5 tumors, germline Carney-complex-associated PRKAR1A mutation in 2 patients, and PRKAR1A fusion in 1 tumor. Additionally, sequencing the metastatic case identified CDKN1B and TERT promoter gene mutations. All tumors showed a low tumoral mutational burden and unremarkable copy number alterations except for frequent LOH of 17q24 encompassing the PRKAR1A locus. RNA expression analysis showed increased expression of several markers including novel PRUNE2, and usual markers like inhibin and calretinin. Our study showed that while LCCSCTs have been reported in the setting of cancer predisposition syndromes, the majority of these tumors occur sporadically. PRKAR1A alterations were present in all cases and appear to be the major driver in LCCSCTs. It remains to be determined whether malignant progression may be caused by additional driver mutations.
Asunto(s)
Complejo de Carney , Tumor de Células de Sertoli , Neoplasias Testiculares , Masculino , Humanos , Tumor de Células de Sertoli/genética , Tumor de Células de Sertoli/patología , Complejo de Carney/genética , Complejo de Carney/patología , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Mutación , Síndrome , Factores de Transcripción/genéticaRESUMEN
BACKGROUND AND AIMS: Pediatric neuroendocrine tumors (NET) of the GI tract are rare and appendiceal NET are typically incidental. Few studies have been done in the pediatric population and practice guidelines are mainly based on adult data. There are currently no diagnostic studies specific for NET. Our study aimed to identify clinical, radiological, and pathological findings in pediatric appendiceal NET, test criteria for follow up surgical treatment, review potential prognostic pathological findings, and possible pre-operative diagnostic radiological studies. MATERIALS AND METHODS: A retrospective data search was conducted for well-differentiated NET of the appendix in patients ≤21 years between 1/1/2003 and 7/1/2022. Available clinical, radiologic, pathological, and follow-up information was recorded. RESULTS: Thirty-seven patients with appendiceal NET were identified. No masses were reported in the patients who underwent presurgical imaging. Appendectomy samples showed NET (0.2->4 cm), most located in the tip. Most cases were WHO G1 (34/37), with negative margins (n = 25). Sixteen cases extended to the subserosa/mesoappendix (pT3). Lymphovascular (6), perineural (2), and both lymphovascular and perineural invasion were also noted (2). The specified tumor stages were pT1 (10/37), pT3 (16/37), and pT4 (4/37). Patients who underwent laboratory testing for chromogranin A (20) and urine 5HIAA (11) had normal limits. Subsequent surgical resection was recommended in 13 cases and performed in 11. To date, all patients have no recurrent or additional metastatic disease. CONCLUSIONS: Our study showed that all pediatric well-differentiated appendiceal NET were incidentally found as part of acute appendicitis management. Most NET were localized with low-grade histology. Our small cohort support the previously suggested management guidelines with follow up resection in certain cases. Our radiologic review didn't identify a best modality for NET. Comparing cases with and without metastatic disease, no tumors under 1 cm had metastasis, but serosal and perineural invasion along with G2 status were associated with metastasis in our limited study.
Asunto(s)
Neoplasias del Apéndice , Apéndice , Tumores Neuroendocrinos , Adulto , Humanos , Niño , Adolescente , Apéndice/patología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/cirugía , Neoplasias del Apéndice/epidemiología , Estudios RetrospectivosRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune, chronic, and heterogenous disease with organ damage resulting from immune complex deposition and inflammatory infiltrates. Antimalarial drugs, such as hydroxychloroquine (HCQ), are cornerstone immunomodulators for the treatment of SLE. Rarely, HCQ toxicity can occur, leading to devastating outcomes. We report a case of a patient with SLE on HCQ who presented with a rapid onset of large pericardial effusion and a dramatically decreased left ventricular ejection fraction. Endomyocardial biopsy was positive for curvilinear bodies, confirming the diagnosis of hydroxychloroquine cardiotoxicity. Hydroxychloroquine cardiomyopathy is a rare but life-threatening medication side effect. It is important to consider it in any patient taking the medication who presents with a new onset or worsening symptoms of heart failure.
RESUMEN
BACKGROUND & AIMS: Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea, and poor weight gain, the causes of which were not identified through routine clinical testing. We aimed to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1188delC/188delC patients. METHODS: Gastric fundic, antral, and duodenal organoids were generated using induced pluripotent stem cell lines from a PDX1188delC/188delC patient and an isogenic induced pluripotent stem cell line where the PDX1 point mutation was corrected. RESULTS: Patient-derived PDX1188delC/188delC antral organoids exhibited an intestinal phenotype, whereas intestinal organoids underwent gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsy specimens from both PDX1188delC/188delC patients, which recapitulated the organoid phenotypes. Moreover, antral biopsy specimens also showed increased parietal cells and lacked G cells, suggesting loss of antral identity. All organoid pathologies were reversed upon CRISPR-mediated correction of the mutation. CONCLUSIONS: These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies.
Asunto(s)
Células Madre Pluripotentes Inducidas , Organoides , Diferenciación Celular , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Metaplasia/metabolismo , Mutación , Organoides/metabolismo , EstómagoAsunto(s)
Sarcoma , ARN Helicasas DEAD-box/genética , Humanos , Riñón , Ribonucleasa III/genética , Sarcoma/diagnósticoRESUMEN
OBJECTIVES: Abdominal aortic coarctation and hypoplasia are uncommon diseases, recognized most often in pediatric-aged individuals. Comprehensive studies regarding the pathologic spectrum of these aortopathies are nonexistent. This investigation was undertaken to better define the histologic and morphologic character of abdominal aortic narrowings affecting children and assess its potential relevance to contemporary clinical practice. METHODS: Aortic specimens obtained during open operations in children being treated for symptomatic, noninflammatory abdominal aortic narrowings at the University of Michigan were subjected to histologic study after hematoxylin and eosin, Movat, Verhoeff Van Gieson, and Masson's trichrome preparations. Microscopic findings were correlated with the anatomic aortic images. In addition, a detailed review was completed of all prior reports in the English literature that included images depicting the histologic character of noninflammatory abdominal aortic narrowings in children. RESULTS: Among a series of 67 pediatric-aged individuals undergoing open surgical interventions for abdominal aortic narrowings, eight children ranging in age from 9 months to 18 years, had adequate aortic tissue available for study. The loci of the specimens paralleled the anatomic sites of segmental coarctations observed in the entire series, with involvement of the suprarenal abdominal aorta (n = 3), intrarenal aorta (n = 2), and infrarenal aorta (n = 1). Diffusely hypoplastic abdominal aortas (n = 2) included one case of a de facto aortic duplication, represented by a channel that paralleled the narrow native aorta and gave origin to celiac artery branches, as well as the superior mesenteric and renal arteries. Concentric or eccentric intimal fibroplasia was observed in every aorta, often with internal elastic fragmentation and duplication (n = 4). Media abnormalities included elastic tissue disorganization (n = 3) and focal medial fibrosis (n = 1). Organizing luminal thrombus occurred in two infants. Coexistent ostial stenoses of the celiac, superior mesenteric, or renal arteries were observed in all but the only child who had an infrarenal aortic coarctation. Neurofibromatosis type 1 affected one child whose histologic findings were indistinguishable from those of the other children. A review of prior published histologic images of abdominal aortic coarctation and hypoplasia affecting children from other centers revealed a total of 14 separate reports, each limited to single case photomicrographs, of which 11 exhibited intimal fibroplasia. CONCLUSIONS: Intimal fibroplasia is a common accompaniment of developmental abdominal aortic coarctation and hypoplasia. It is posited that intimal fibroplasia, which is likely progressive in instances of abnormal shear stresses in these diminutive vessels, may contribute to less salutary outcomes after endovascular and certain open reconstructions of pediatric abdominal aortic narrowings.
Asunto(s)
Aorta Abdominal , Coartación Aórtica , Adolescente , Aorta Abdominal/anomalías , Aorta Abdominal/patología , Aorta Abdominal/cirugía , Coartación Aórtica/patología , Coartación Aórtica/cirugía , Niño , Preescolar , Humanos , Lactante , Procedimientos de Cirugía PlásticaRESUMEN
BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.
Asunto(s)
Lesiones Precancerosas , Neoplasias de las Glándulas Salivales , Adolescente , Adulto , Biopsia con Aguja Fina , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Lesiones Precancerosas/diagnóstico , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología , Adulto JovenRESUMEN
BACKGROUND: Thyroid fine needle aspiration (T-FNA) is a mainstay in management of thyroid nodules. However, the preparation of T-FNA specimens varies across institutions. Prior studies have compared diagnostic rates between different specimen preparations of T-FNA specimens and their associated advantages and disadvantages. However, few have compared the rates of all diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) between liquid-based preparations (LBPs) and a combination of LBP and conventional smear (CS) preparations. Our study compares TBSRTC diagnostic rates between these 2 cohorts and correlates cytologic diagnoses with subsequent thyroid resections to evaluate rates of neoplasia (RON) and malignancy (ROM). METHODS: 584 consecutive thyroid FNA specimens were collected and stratified by preparation type (ThinPrep [TP] vs. CS & TP). Diagnostic rates for each TBSRTC diagnostic category were calculated. The institution's electronic medical records database was searched for histologic diagnoses of previously sampled thyroid nodules to evaluate the RON and ROM. RESULTS: Of 584 thyroid FNA specimens, 73 (12.5%) and 511 (87.5%) were evaluated by TP only and CS & TP, respectively, reflecting the predominance of rapid on-site evaluation (ROSE) with CS for T-FNAs at our institution. Of the TP only and CS & TP cohorts, 29 (39.7%) and 98 (19.2%) had subsequent resections, respectively. The frequency of non-diagnostic cases was lower in the CS & TP cohort (12.7% vs. 26%). While the diagnostic rate of follicular lesion of undetermined significance was similar for both cohorts, SFN categorization was only utilized in the CS & TP cohort (1.5% vs. 0%). Although RON and ROM were similar between cohorts in many of the TBSRTC categories, there was a higher RON associated with non-diagnostic specimens in the TP only cohort when the denominator included all non-diagnostic cases. CONCLUSION: The combination of CS and LBP may potentially decrease the non-diagnostic rate of T-FNA specimens as well as the number of passes required for diagnosis, particularly with ROSE. Evaluation of morphologic features highlighted in conventional smears may facilitate diagnostic categorization in the "suspicious for follicular neoplasm" category.
Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Biopsia con Aguja Fina , Estudios de Cohortes , Humanos , Estudios Retrospectivos , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugíaRESUMEN
BACKGROUND: Granulomatous intestinal inflammation may be associated with aggressive Crohn's disease (CD) behavior. However, this has not been confirmed, and it is unknown if associated disease complications are preventable. METHODS: This is a retrospective cohort of patients younger than 21 years at CD diagnosis (November 1, 2005 to November 11, 2015). Clinical information was abstracted, including dates of starting medications and the timing of perianal fistula or stricture development, if any. Diagnostic pathology reports were reviewed, and a subset of biopsy slides were evaluated by a blinded pathologist. Patients were excluded if perianal fistula or stricture developed within 30 days after CD diagnosis. Medications were included in analyses only if started >90 days before development of perianal fistula or stricture. RESULTS: In total, 198 patients were included. Half (54%) had granulomas at diagnosis. Granulomas were associated with a greater than 3-fold increased risk of perianal fistula (hazard ration [HR]â =â 3.24; 95% confidence interval CI], 1.40-7.48). Immunomodulator and anti-tumor necrosis factor-α (anti-TNF) therapy were associated with 90% (HR, =â 0.10; 95% CI, 0.03-0.42) and 98% (HR, =â 0.02; 95% CI, 0.01-0.10) reduced risk of perianal fistula, respectively. Patients with granulomatous inflammation preferentially responded to anti-TNF therapy with reduced risk of perianal fistula. The presence of granulomas was not associated with risk of stricture. Immunomodulator and anti-TNF therapy were associated with 96% (HR, =â 0.04; 95% CI, 0.01-0.22) and 94% (HR, =â 0.06; 95% CI, 0.02-0.20) reduced risk of stricture, respectively. CONCLUSIONS: Granulomas are associated with increased risk of perianal fistula but not stricture. Steroid sparing therapies seem to reduce the risk of both perianal fistula and stricture. For those with granulomas, anti-TNF-α therapy greatly reduced the risk of perianal fistula development, whereas immunomodulators did not.
Asunto(s)
Enfermedad de Crohn , Biopsia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Granuloma/etiología , Humanos , Estudios Retrospectivos , Inhibidores del Factor de Necrosis TumoralRESUMEN
Secretory carcinoma (SC), previously known as mammary analogue secretory carcinoma, is a rare salivary gland neoplasm that typically presents as a slow-growing painless lesion in the head and neck. SC occurs mainly in adults but has been described in children with the youngest reported patient diagnosed at five years of age. In children the gender distribution has been reported as female to male ratio of 1:1.2. SC is generally considered a low-grade malignancy with characteristic morphological features and immunological profile. SC also harbors ETV6-NTRK3 fusion (t(12;15)(p13:q25)). Surgical resection with or without lymph node dissection is the standard treatment, with generally favorable clinical outcomes. Here we present a single institution case series of six patients (ages 9-21) with SC and a review of the previously described pediatric cases. Our small series showed male predominance in pediatric patients with predominantly low-grade and stage tumors. All cases underwent complete surgical resections and when follow up is available there was no evidence of recurrences or metastases. To the best of our knowledge, this is the only SC case series comprised exclusively of pediatric and youth patients.
Asunto(s)
Carcinoma , Carcinoma Secretor Análogo al Mamario , Neoplasias de las Glándulas Salivales , Adolescente , Biomarcadores de Tumor/genética , Neoplasias de la Mama , Carcinoma/patología , Niño , Femenino , Humanos , Masculino , Carcinoma Secretor Análogo al Mamario/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/cirugía , Adulto JovenRESUMEN
Anaplastic sarcoma of the kidney (ASK) is a rare renal tumor for which less than thirty cases have been described in the literature to date. Diagnosis of ASK is primarily based on histology, which features solid spindle cell neoplastic islands arranged in a fascicular pattern, prominent anaplastic nuclear morphology, brisk mitoses, and multiple multiloculated cysts lined by hobnail epithelium reminiscent of cystic nephroma. Chondroid or rhabdomyocytic differentiation is often present within the sarcoma. It has been recently suggested that this tumor entity belongs to the DICER1 syndrome tumors based on identification of DICER1 mutations. We report on a case of this rare tumor found in a twenty-month-old female. In addition to the typical histologic findings of ASK, this case also displayed heterologous neuroblastic-gangliocytic differentiation, which has not been previously described in the literature. TP53 and BRAF v600E had aberrant immunostaining. Chromosomal microarray and genomic sequencing revealed loss of chromosome 10 p15.3-p11.2 and both somatic and germline DICER1 mutations, consistent with recent research and further supporting the classification of this tumor within the DICER1 syndrome associated tumors.
Asunto(s)
Quistes , Neoplasias Renales , Síndromes Neoplásicos Hereditarios , Sarcoma , ARN Helicasas DEAD-box/genética , Femenino , Mutación de Línea Germinal , Humanos , Lactante , Riñón/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Mutación , Ribonucleasa III/genética , Sarcoma/genéticaRESUMEN
OBJECTIVES: Pediatric thyroid cancer is rare. Most cases are well-differentiated thyroid cancers (WDTCs). However, gross laryngotracheal invasion of WDTCs is unusual. This report details the first case in English medical literature of a pediatric WDTC invading the trachea. METHODS: Thyroid stimulating hormone, free triiodothyronine, free thyroxine, thyroglobulin, parathyroid hormone, calcitonin, thyroglobulin antibody, chest magnetic resonance imaging, neck ultrasound, neck computed tomography, and fine needle aspiration were performed. RESULTS: A 9-year-old boy with moderate persistent asthma presented with increasing upper respiratory symptoms. Spirometry suggested a fixed upper airway obstruction. Chest x-ray revealed a left tracheal shift, and chest magnetic resonance imaging identified a right thyroid mass. Thyroglobulin level was 809 ng/mL (normal, ≤33 ng/mL). Results of thyroid stimulating hormone, free triiodothyronine, free thyroxine, parathyroid hormone, calcitonin, and thyroglobulin antibody were normal. Neck ultrasound revealed 2 right thyroid lobe nodules. Neck computed tomography revealed tracheal compression. Fine needle aspiration of the largest nodule yielded atypia of undetermined significance. Bronchoscopy findings at his local hospital were concerning for tracheal invasion. He underwent total thyroidectomy, cricotracheal resection, reconstruction, and radioactive iodine therapy (220 mCi). Pathology demonstrated a well-differentiated papillary thyroid carcinoma without solid or diffuse sclerosing subtype components. Tumor cytogenetic and single nucleotide polymorphism microarray studies showed normal findings. One year postoperatively, neck ultrasound demonstrated no recurrence, and thyroglobulin levels were undetectable while on levothyroxine therapy. CONCLUSION: Pediatric WDTC invading the trachea has not been reported.
RESUMEN
BACKGROUND: Afirma gene expression classifier (GEC) is an adjunct to thyroid fine needle aspiration shown to improve pre-operative risk assessment and reduce unnecessary surgery of indeterminate thyroid nodules. Genomic sequencing classifier (GSC) is a newer version aiming to improve specificity and positive predictive value (PPV) of Afirma testing. There are limited studies comparing GSC vs GEC. This study was undertaken to compare these classifiers in terms of diagnostic performance and effect on clinical management of indeterminate thyroid nodules. METHODS: The study cohort consisted of patients with thyroid nodules that had a recurrent cytologic diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and were tested by either GEC or GSC. Patient demographics, nodule size, and clinical follow-up were recorded. Benign call rate (BCR) of Afirma testing, rate of subsequent surgery (RSS), rate of histology-confirmed malignancy (RHM), as well as diagnostic sensitivity, specificity, PPV, negative predicative value (NPV), and accuracy were calculated and compared between GSC and GEC cohorts. RESULTS: Among 264 AUS/FLUS thyroid nodules, 127 and 137 were tested with GEC and GSC, respectively. Compared to GEC, GSC demonstrated increased BCR (77.3% vs 52%), decreased RSS (31.4% vs 51.2%), greater RHM (29% vs 9.8%) associated with a suspicious Afirma result, as well as improved specificity (82.8% vs 54.5%), PPV (29% vs 9.8%), and diagnostic accuracy (83.9% vs 56.7%), while maintaining high sensitivity and NPV. CONCLUSION: Afirma GSC substantially improved BCR, RSS, RHM, and diagnostic performance, enhancing appropriate triage and thereby helped avoid unnecessary surgery in AUS/FLUS thyroid nodules.
Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Genoma/genética , Genómica , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/genética , Nódulo Tiroideo/metabolismo , Nódulo Tiroideo/patología , Adulto JovenRESUMEN
BACKGROUND: Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the characteristics of children undergoing resection of a primary lung lesion and to identify preoperative risk factors for malignancy. METHODS: A retrospective cohort study was conducted by using an operative database of 521 primary lung lesions managed at 11 children's hospitals in the United States. Multivariable logistic regression was used to examine the relationship between preoperative characteristics and risk of malignancy, including pleuropulmonary blastoma (PPB). RESULTS: None of the 344 prenatally diagnosed lesions had malignant pathology (P < .0001). Among 177 children without a history of prenatal detection, 15 (8.7%) were classified as having a malignant tumor (type 1 PPB, n = 11; other PPB, n = 3; adenocarcinoma, n = 1) at a median age of 20.7 months (interquartile range, 7.9-58.1). Malignancy was associated with the DICER1 mutation in 8 (57%) PPB cases. No malignant lesion had a systemic feeding vessel (P = .0427). The sensitivity of preoperative chest computed tomography (CT) for detecting malignant pathology was 33.3% (95% confidence interval [CI]: 15.2-58.3). Multivariable logistic regression revealed that increased suspicion of malignancy by CT and bilateral disease were significant predictors of malignant pathology (odds ratios of 42.15 [95% CI, 7.43-340.3; P < .0001] and 42.03 [95% CI, 3.51-995.6; P = .0041], respectively). CONCLUSIONS: In pediatric lung masses initially diagnosed after birth, the risk of PPB approached 10%. These results strongly caution against routine nonoperative management in this patient population. DICER1 testing may be helpful given the poor sensitivity of CT for identifying malignant pathology.
Asunto(s)
Neoplasias Pulmonares/patología , Blastoma Pulmonar/patología , Preescolar , Estudios de Cohortes , ARN Helicasas DEAD-box/genética , Femenino , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Mutación , Metástasis de la Neoplasia/genética , Embarazo , Diagnóstico Prenatal , Blastoma Pulmonar/diagnóstico por imagen , Blastoma Pulmonar/genética , Blastoma Pulmonar/cirugía , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Estudios Retrospectivos , Ribonucleasa III/genética , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Cytologic detection of malignant cells in pleural, peritoneal, or pericardial effusion most likely indicates advanced stage of malignant disease. There are a few studies updating the categorization of malignant effusions. METHODS: The electronic pathology database was searched to identify consecutive cases of malignant effusion during a 6-year period. Patient age and gender, origins of known malignancy, and cytologic diagnoses were recorded and summarized. RESULTS: A total of 1059 specimens included 561 (53%) pleural, 441 (41.6%) peritoneal, and 57 (5.4%) pericardial fluids. Most of the pleural (516, 92.0%), peritoneal (418, 94.8%), and pericardial (53, 93.0%) specimens were derived from patients with a single known malignancy. More common origins involving pleural fluid were lung (152, 27.1%) followed by breast (103, 18.4%) and gastrointestinal tract (76, 13.5%). The most common etiology for women and men was breast (102, 30.8%) and lung (67, 36.2%), respectively. More common origins involving peritoneal fluid were gastrointestinal (158, 35.8%) and gynecologic (156, 35.4%) tracts, and breast (46, 10.4%). The most common etiology for women and men was Mullerian (156, 55.5%) and gastrointestinal tract (94, 68.6%), respectively. Most common origins involving the pericardial fluid were breast (20, 37.7%) and lung (17, 29.8%). Breast and lung were the most common etiology for women (20, 57.1%) and men (8, 44.4%), respectively. CONCLUSIONS: Breast and lung remain to be the most common origin of both malignant pleural and pericardial effusion for women and men, respectively. The most common origin involving peritoneal effusion is Mullerian for women and gastrointestinal tract for men.