Intratesticular Mullerian Serous Borderline Tumor With Microinvasion: A Rare Tumor and Review of the Literature.

Ovarian-type (ie, Mullerian) epithelial tumors occurring in the testicular and paratesticular regions are exceptionally rare, with only a handful reported worldwide. Serous tumors are the most frequently encountered subtype among these rare tumors. The pathogenesis of these tumors within the testicular and paratesticular regions remains a subject of intrigue and debate, with various hypotheses attempting to explain their presence in the paratestis region, where most tumors occur. However, our understanding of the pathogenesis of intratesticular tumors is limited. To date, 11 known examples of intratesticular serous Mullerian tumors have been reported globally. In this report, we present an extraordinary tumor, an intratesticular Mullerian serous borderline tumor with foci of microinvasion, in a 38-year-old male patient. This tumor exhibits histological features similar to their ovarian counterparts and is confirmed through an immunohistochemical panel. Our report underscores the extreme rarity of these tumors, emphasizes the importance of heightened awareness among clinicians and pathologists, and provides valuable insights into their complex development and histogenesis. This contribution aims to enhance diagnostic precision and optimize therapeutic strategies for similar tumors.

Report of a Primary Testicular Embryonal Rhabdomyosarcoma.

Primary testicular rhabdomyosarcoma is a rare pediatric genitourinary tumor with few cases reported in the literature. The clinical presentation is identical to that of other common testicular neoplasms. Diagnosis entails careful microscopic examination and immunohistochemical analysis to rule out other primary testicular malignancies. Treatment consists of radical orchiectomy and adjuvant chemotherapy with possible retroperitoneal lymph node dissection. This multimodal approach is required to improve survival outcomes and reduce disease recurrence. We present the case of a primary testicular embryonal rhabdomyosarcoma in a 19-year-old male who presented with a rapidly, enlarging, painless testicular mass. He was treated with radical orchiectomy and adjuvant chemotherapy. Once found with metastatic disease, he then received salvage chemotherapy and radiotherapy without success.

The Role of microRNAs in the Gonocyte Theory as Target of Malignancy: Looking for Potential Diagnostic Biomarkers.

Some pediatric patients with cryptorchidism preserve cells with gonocyte characteristics beyond their differentiation period, which could support the theory of the gonocyte as a target for malignancy in the development of testicular neoplasia. One of the key molecules in gonocyte malignancy is represented by microRNAs (miRNAs). The goal of this review is to give an overview of miRNAs, a class of small non-coding RNAs that participate in the regulation of gene expression. We also aim to review the crucial role of several miRNAs that have been further described in the regulation of gonocyte differentiation to spermatogonia, which, when transformed, could give rise to germ cell neoplasia in situ, a precursor lesion to testicular germ cell tumors. Finally, the potential use of miRNAs as diagnostic and prognostic biomarkers in testicular neoplasia is addressed, due to their specificity and sensitivity compared to conventional markers, as well as their applications in therapeutics.

Genitourinary Tract Tumors in Children: An Update.

BACKGROUND: Genitourinary tract tumors in children are less common than in adults. Most of these tumors have different genetic backgrounds, clinical presentation, and oncologic behavior than their adult counterpart. As a result of low prevalence in children, some of the treatment approaches and recommendations are based on treatment experience in adult patients. However, thanks to scientific and technological development, survival rates have risen considerably. OBJECTIVE: This paper presents a review of the principal features of the tumors involving the genitourinary tract in children and an update in genetic background, diagnosis, and treatment. METHODS: A narrative review was performed on published literature about genitourinary tract tumors in pediatric patients. Papers presented in English and Spanish literature were reviewed. PubMed, Science Direct, and SciELO databases were used to collect information and present this article. RESULTS: Kidney tumors are the most common type of genitourinary tumors in children. Among those, Wilms tumor represents the majority of cases and shows the successful work of clinical trial groups studying this tumor type. Other tumors involving the genitourinary tract in children include Rhabdomyosarcoma, Transitional cell carcinoma, Testicular, and Adrenal tumors. CONCLUSION: Genitourinary tract tumors in children represent significant morbidity and economic burden, so awareness in early diagnosis represents improvement in treatment, clinical, and oncological outcomes.

Disfunções endócrinas mais comuns e que podem afetar a atividade reprodutiva de cães / Endocrine dysfunctions that can affect reproductive activity in dogs

As disfunções hormonais podem interagir com eixo hipotalamo-hipófise-gônadas (H/H/G) resultando em alteração da espermatogênese e impactando negativamente a fertilidade dos machos. As endocrinopatias na espécie canina são mais frequentes nas fêmeas e muitas vezes os sinais clínicos iniciais envolvem alopecias e alterações de peso, comportamento e de metabolismo. As disfunções hormonais comuns em cães machos incluem o hipotireoidismo, hiperplasia prostática benigna e os tumores testiculares. Cães idosos geralmente apresentam alterações hormonais dependentes da idade, mas a literatura é escassa e conflitante em relação a esta condição, assim o objetivo dessa revisão é informar e atualizar conceitos relacionados às disfunções hormonais que podem causar infertilidade em cães machos com vistas a ferramentas mais modernas de diagnósticos e avaliação seminal.(AU)

Hormonal dysfunctions may interact with hypothalamus, pituitary, gonads (H/H/G) axis resulting in altered spermatogenesis and negatively impacting male fertility. Endocrinopathies in the canine species are more frequent in females and often the initial clinical signs involve alopecia and changes in weight, behavior, and metabolism. Common hormonal dysfunctions in male dogs include hypothyroidism, benign prostatic hyperplasia, and testicular tumors. Older dogs usually present age- dependent hormonal changes, but the literature is scarce and conflicting regarding this condition, thus the aim of this review is to inform and update concepts related to hormonal dysfunctions that can cause infertility in male dogs with a view to more modern diagnostic tools and seminal evaluation.(AU)

Sarcoma fibromixoide de baixo grau em região paratesticular: um relato de caso / Low-grade fibromyxoid sarcoma in paratesticular area: a case report

Objetivos: relatar um caso raro de sarcoma fibromixoide de baixo grau (SFMBG) em uma localização incomum de modo a reforçar aspectos histopatológicos e imunoistoquímicos relevantes para o reconhecimento desta entidade e o adequado diagnóstico diferencial de massas paratesticulares. Relato de caso: homem de 20 anos, com massa escrotal à direita, cuja análise histopatológica demonstrou a presença de tecido fibroso com áreas mixoides e predominância de células fusiformes. A imunoistoquímica foi positiva para vimentina, com índice de Ki67 de 2%, e negativa para S100, CD-34, beta-catenina, desmina e miogenina. Conclusões: caso raro de SFMBG na região paratesticular que reforça a importância da histopatologia e da imunoistoquímica no diagnóstico desse tumor. Apesar da característica histológica benigna, o SFMBG apresenta altas taxas de recorrência e metástases, sendo essencial o seguimento do paciente.

Objectives: to report a rare case of low-grade fibromyxoid sarcoma (LGFMS) in an unusual location in order to reinforce histopathological and immunohistochemical aspects relevant to the recognition of this entity and the adequate differential diagnosis of paratesticular masses. Case report: 20-year-old man, with a right scrotal mass and histopathological analysis showing the presence of fibrous tissue with myxoid areas and a predominance of spindle cells. Immunohistochemistry was positive for vimentin, with a Ki67 index of 2%, and negative for S100, CD-34, beta-catenin, desmin and myogenin. Conclusions: rare case of LGFMS in the paratesticular region that reinforces the importance of histopathology and immunohistochemistry in the diagnosis of this tumor. Despite the benign histological characteristic, LGFMS has high rates of recurrence and metastasis, and patient follow-up is essential.

Testicular morphometry of rats with Walker 256 tumor supplemented with L-glutamine

Glutamine is often used to treat metabolic changes associated with anorexia-cachexia syndrome in patients with malignant neoplasms. Walker 256 tumor is an excellent model for studying these changes associated with cancer in different organs, including injuries in testicular functions. However, the effects of supplementing glutamine on testicular morphometry in this model have not yet been investigated. Thus, the objective of this study was to evaluate the effect of L-glutamine supplementation on testicular morphometry in rats transplanted with Walker 256 tumor cells. Forty puberty Wistar rats were divided into four groups: control without L-glutamine (C); control supplemented with L-glutamine (CG); inoculated with Walker 256 tumor cells (WT) and inoculated with Walker 256 tumor cells and supplemented with L-glutamine (WTG). The testicles were removed, weighed, fixed in Bouin, and included in paraffin for histomorphometric analysis. Walker 256 tumor caused quantitative changes in the tubular and intertubular compartments and tunica albuginea, with reductions in the percentages of lumen and tunica albuginea, number of Sertoli cells per gram of testis; number of Leydig cells; percentage of blood vessels and connective tissue in intertubule. However, glutamine supplementation prevented part of these changes caused by the tumor, presenting mainly a protective effect on the tunica albuginea and percentage of blood and lymph vessels in the intertubule. These results indicate the potential of L-glutamine was able to recover for testicular dysfunction associated with cancer.(AU)

Neoplasia testicular em jaguatirica (Leopardus pardalis Linnaeus, 1758) / Testicular neoplasm in ocelot (Leopardus pardalis Linnaeus, 1758) / Neoplasia testicular en ocelote (Leopardus pardalis Linnaeus, 1758)

O crescimento neoplásico é definido como proliferação autônoma e progressiva das células, que na maioria dos casos está correlacionada à presença de massa ou tumor. As neoplasias são pouco relatadas em felinos silvestres e a indicação quase sempre é a exérese da neoformação. Há um significativo aumento na incidência de neoplasias em animais silvestres mantidos sob cuidados humanos, provavelmente relacionadas ao aumento da taxa de longevidade dos animais em zoológicos. Um exemplar de jaguatirica (Leopardus pardalis) apresentou aumento de volume do testículo direito e foi submetido a exames de imagens e laboratoriais. O exame citológico e histopatológico foi conclusivo para seminoma, e o paciente foi submetido a orquiectomia unilateral. O felino apresentou recuperação satisfatória e será acompanhado pelos próximos anos para o monitoramento da neoplasia no organismo. Esse é o primeiro relato de seminoma em jaguatirica.(AU)

Neoplastic growth is defined as an autonomous and progressive proliferation of cells which, in most cases, is correlated with the presence of a mass or tumor. Neoplasms are rarely reported in wild cats and the indicated treatment is almost always the excision of the new formation. There is a significant increase in the incidence of neoplasms in wild animals under human care, probably related to the increase in the longevity rate of animals kept in zoos. A specimen of ocelot (Leopardus pardalis) showed an increase in the volume of the right testicle and the patient was submitted to imaging and laboratory tests. The diagnosis was conclusive for seminoma and the patient underwent a unilateral orchiectomy. The patient has recovered well and will be followed-up over the next few years to monitor the presence of neoplasm in the body. This is the first report of seminoma in an ocelot.(AU)

El crecimiento de una neoplasia se caracteriza por la proliferación autónoma y progresiva de las células, que en la mayoría de los casos está relacionada con la presencia de una masa o un tumor. Existen pocos relatos de tumores en felinos salvajes, en los que está indicada casi siempre su extirpación. Se ha comprobado un aumento significativo de las neoplasias en animales salvajes bajo cuidados humanos, probablemente relacionado con la mayor longevidad de esos animales en zoológicos. Un ocelote (Leopardus pardalis) presentó aumento de volumen del testículo derecho. Fueran realizados exámenes de laboratorio y de imágenes. Los exámenes tológicos e histopatológicos evidenciaron la presencia de un seminoma, por lo que fue realizada una orquiectomía unilateral. El felino tuvo una recuperación satisfactoria y será controlado durante los próximos años ante la eventual aparición de otros tumores, recidiva o metástasis. Este es el primer relato de un seminoma en un ocelote.(AU)

Neoplasia testicular em jaguatirica (Leopardus pardalis – Linnaeus, 1758) / Testicular neoplasm in ocelot (Leopardus pardalis – Linnaeus, 1758) / Neoplasia testicular en ocelote (Leopardus pardalis – Linnaeus, 1758)

O crescimento neoplásico é definido como proliferação autônoma e progressiva das células, que na maioria dos casos está correlacionada à presença de massa ou tumor. As neoplasias são pouco relatadas em felinos silvestres e a indicação quase sempre é a exérese da neoformação. Há um significativo aumento na incidência de neoplasias em animais silvestres mantidos sob cuidados humanos, provavelmente relacionadas ao aumento da taxa de longevidade dos animais em zoológicos. Um exemplar de jaguatirica (Leopardus pardalis) apresentou aumento de volume do testículo direito e foi submetido a exames de imagens e laboratoriais. O exame citológico e histopatológico foi conclusivo para seminoma, e o paciente foi submetido a orquiectomia unilateral. O felino apresentou recuperação satisfatória e será acompanhado pelos próximos anos para o monitoramento da neoplasia no organismo. Esse é o primeiro relato de seminoma em jaguatirica.

Neoplastic growth is defined as an autonomous and progressive proliferation of cells which, in most cases, is correlated with the presence of a mass or tumor. Neoplasms are rarely reported in wild cats and the indicated treatment is almost always the excision of the new formation. There is a significant increase in the incidence of neoplasms in wild animals under human care, probably related to the increase in the longevity rate of animals kept in zoos. A specimen of ocelot (Leopardus pardalis) showed an increase in the volume of the right testicle and the patient was submitted to imaging and laboratory tests. The diagnosis was conclusive for seminoma and the patient underwent a unilateral orchiectomy. The patient has recovered well and will be followed-up over the next few years to monitor the presence of neoplasm in the body. This is the first report of seminoma in an ocelot.

El crecimiento de una neoplasia se caracteriza por la proliferación autónoma y progresiva de las células, que en la mayoría de los casos está relacionada con la presencia de una masa o un tumor. Existen pocos relatos de tumores en felinos salvajes, en los que está indicada casi siempre su extirpación. Se ha comprobado un aumento significativo de las neoplasias en animales salvajes bajo cuidados humanos, probablemente relacionado con la mayor longevidad de esos animales en zoológicos. Un ocelote (Leopardus pardalis) presentó aumento de volumen del testículo derecho. Fueran realizados exámenes de laboratorio y de imágenes. Los exámenes tológicos e histopatológicos evidenciaron la presencia de un seminoma, por lo que fue realizada una orquiectomía unilateral. El felino tuvo una recuperación satisfactoria y será controlado durante los próximos años ante la eventual aparición de otros tumores, recidiva o metástasis. Este es el primer relato de un seminoma en un ocelote.

Tumor desmoplásico de célula pequeña y redonda paratesticular/testicular: reporte de caso y revisión de la literatura / Paratesticular/testicular desmoplastic round small cell malignant tumor: case report and literature review

Resumen El tumor desmoplásico de célula redonda y pequeña (TDCRP) es una patología neoplásica maligna agresiva y poco común. Afecta predominantemente a hombres entre la segunda y tercera década de la vida. Los pacientes que la padecen tienen un pronóstico pobre, con una supervivencia global a 5 años de hasta el 30%. Por lo general se presenta como una masa en la cavidad abdominal, frecuentemente multifocal. Para su tratamiento se recomienda un enfoque multimodal con cirugía, quimioterapia y radioterapia. Poco más de 20 casos de TDCRP a nivel testicular/paratesticular se han reportado en la literatura. A continuación, se presenta un caso ilustrativo en esta localización, se discute el caso y se realiza revisión de la literatura.

Abstract Desmoplastic small round cell tumor (DSRCT) is an aggressive and rare malignant neoplasm. It mainly affects young men in their twenties and thirties. Patients with it have a poor prognosis, with a 5-year survival rate of up to 30%. It generally presents as a mass in the abdominal cavity, often multifocal. A multimodal approach is recommended for its treatment, with surgery, chemotherapy, and radiotherapy. Just over 20 cases of testicular/paratesticular DSRCT have been reported in the literature. Below, we present an illustrative case in this location, we discuss the case and review the literature.

Sarcomatoid Type of Paratesticular Malignant Mesothelioma in a Dry-Cleaning Worker Exposed to Asbestos and Diagnostic Value of WT-1.

Of the 3 major histologic types of malignant paratesticular mesothelioma (MPM) (epithelial, sarcomatoid, and biphasic), many cases of epithelial and biphasic mesothelioma have been reported in the literature. Pure sarcomatoid MPM is the least common but the most aggressive of the 3 major histologic types of mesothelioma cells. It is limited to only 2 cases in the literature The sarcomatoid type of MPM can be confused clinically and histologically with true sarcomas because it is rarely seen. We present a case who had been exposed to asbestos for years due to his involvement in the dry-cleaning industry and who was diagnosed with the sarcomatoid type of MPM but had a relatively prolonged survival not usually seen with this tumor. This report also emphasizes the significance of an immunohistochemical examination, focusing especially on the diagnostic role of WT-1.

The relationship of neutrophil to lymphocyte ratio with testicular cancer

ABSTRACT Purpose: To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker. Material and Methods: Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared. Results: Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10±2.13 to 1.62±0.59 postoperatively (p=0.010). Conclusions: NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.

The relationship of neutrophil to lymphocyte ratio with testicular cancer.

PURPOSE: To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker. MATERIAL AND METHODS: Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared. RESULTS: Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10 ± 2.13 to 1.62 ± 0.59 postoperatively (p=0.010). CONCLUSIONS: NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.

Clinical stage I synchronous bilateral testicular germ cell tumor with different histopathology: a case report.

Bilateral testicular germ cell tumors (BTGCT) occur in 1 to 4% of patients with testicular cancer and of these, 10-15% are synchronous. Overall, BTGCT represents less than 0.5% of all new cases of testicular cancer. There are few reports in the literature of synchronous BTGCT with different histology. We present the case of a 30-year-old man who presented to our genitourinary tumor unit with a bilateral increase of testicular volume. After initial assessment, a testicular ultrasound showed the presence of solid tumors in both testes. Staging studies were negative for metastatic disease. The patient was referred to the fertility clinic for sperm banking and later underwent a bilateral radical orchiectomy. The histopathology evaluation revealed a 5.5 cm right-sided mixed germ cell tumor and a 1.5 cm left-sided testicular seminoma. Because patient's poor compliance for surveillance was identified as a risk factor for relapse and poor outcome, adjuvant chemotherapy was favored. The patient underwent one cycle of bleomycin, etoposide and cisplatin (BEP). After four years of follow up, the patient shows no evidence of relapse, either clinically or radiologically. In men unlikely to carry out successful surveillance; active treatment is the preferred option for preventing disease recurrence, even in patients with no risk factors. The physician must consider all available therapeutic measures in this scenario to achieve the best possible therapeutic result.

Mastocitoma de alto grau em bolsa testitular em cão / Mast cell tumor high grade in testicular bag in dog

Mast cell tumor is the most common skin tumor in dogs. Due to mast cell proliferation, the affected animals present clinical symptoms compatible with the release of excess histamine granules present inside these cells leading to changes in the gastrointestinal and vascular tracts with the possibility of causing anaphylactic shock. The diagnosis is made by cytopathological analysis and classified by means of histopathology. Treatment is based on staging, surgical exeresis with antineoplastic chemotherapy and drug treatment to inhibit the effects of histamine release. A dog of 14 years old of Boxer breed was attend complaining of nodulation in the testicular bag with a two month evolution. Animal was diagnosed with mast cell tumor. Treatment was instituted by surgical excision and due to the metastatic possibility in regional lymph node, antineoplastic and drug therapy was indicated, which was not successful due of the person responsible non-adherence to the treatment. Mast cell tumor classified as high grade after histopathological analysis. Animal survived for two months after diagnosis of the disease. Due to the high grade of neoplastic presentation and difficulty in treatment, the animal had low survival, corroborating with data described in the literature regarding the poor prognosis of this tumor type.(AU)

Mastocitoma de alto grau em bolsa testitular em cão / Mast cell tumor high grade in testicular bag in dog

Mast cell tumor is the most common skin tumor in dogs. Due to mast cell proliferation, the affected animals present clinical symptoms compatible with the release of excess histamine granules present inside these cells leading to changes in the gastrointestinal and vascular tracts with the possibility of causing anaphylactic shock. The diagnosis is made by cytopathological analysis and classified by means of histopathology. Treatment is based on staging, surgical exeresis with antineoplastic chemotherapy and drug treatment to inhibit the effects of histamine release. A dog of 14 years old of Boxer breed was attend complaining of nodulation in the testicular bag with a two month evolution. Animal was diagnosed with mast cell tumor. Treatment was instituted by surgical excision and due to the metastatic possibility in regional lymph node, antineoplastic and drug therapy was indicated, which was not successful due of the person responsible non-adherence to the treatment. Mast cell tumor classified as high grade after histopathological analysis. Animal survived for two months after diagnosis of the disease. Due to the high grade of neoplastic presentation and difficulty in treatment, the animal had low survival, corroborating with data described in the literature regarding the poor prognosis of this tumor type.

Testicular Cancer mortality in Brazil: trends and predictions until 2030.

BACKGROUND: Despite the fact that testicular cancer presents good prognosis, wide variations in mortality rates have been reported internationally. In Brazil, mortality trends and estimates have not been fully assessed. The objective of the study presented herein is to analyze the mortality trends for testicular cancer in Brazil in the period 2001-2015 and calculate mortality predictions for the period 2016-2030. METHODS: This is a population-based ecological study that utilized information of the Mortality Information System, on testicular cancer-related deaths in Brazil. Mortality trends were analyzed by Joinpoint regression, and Nordpred was utilized for the calculation of predictions. RESULTS: The mortality rate for men, standardized to the world population, varied between 0.36/100,000 for the year 2001, to 0.41/100,000 for the year 2015. There was an increasing trend for Brazil (APC = 1.3% CI95% 0.6; 2.0) and the Southeast region (APC = 1.5% CI95%0.2; 2.7). When analyzing Brazilian data for the period 2016-2030, predictions indicate 2888 deaths due to testicular cancer, which corresponds to a 26.6% change when compared to the 2011-2015 period. This change is mostly explained by an increase in the risk of death (14.2%) when compared with modifications in the demographic structure (12.4%). CONCLUSIONS: Testicular cancer mortality in Brazil presents increasing trends, and until 2030 these rates continue to increase.

Pathogenesis of Testicular Germ Cell Neoplasia: A Conceptual Approach.

Testicular germ cell tumors are a diverse group of neoplasms, consisting of the prepubertal type 1 tumors, pure teratoma, and pure yolk sac tumor, the type 2 tumors, which are biologically malignant, preceded by germ cell neoplasia in situ, and harbor chromosome 12p abnormalities, and the type 3 tumor, spermatocytic tumor, which features chromosome 9p amplification. These arise in distinct clinical settings, and harbor distinct genetic abnormalities, immunohistochemical properties, and morphologic features. Here we have attempted to unify embryology, morphology, immunohistochemistry, and genetics in order to distill this fascinating group of neoplasms into what we hope is a useful framework for understanding their classification.