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  1. Article ; Online: Anogenital distance in a cohort of 169 infant boys with uni- or bilateral cryptorchidism including 18 boys with vanishing testes.

    Cortes, Dina / Fischer, Margit Bistrup / Hildorf, Andrea E / Clasen-Linde, Erik / Hildorf, Simone / Juul, Anders / Main, Katharina M / Thorup, Jorgen

    Human reproduction (Oxford, England)

    2024  Volume 39, Issue 4, Page(s) 689–697

    Abstract: Study question: Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)?: Summary answer: Length of AGD seemed to differ in different groups of patients with cryptorchidism.: What is known already: ... ...

    Abstract Study question: Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)?
    Summary answer: Length of AGD seemed to differ in different groups of patients with cryptorchidism.
    What is known already: AGD, which is used as an indicator of prenatal androgen action, tends to be shorter in boys with cryptorchidism compared to unaffected boys. Shorter AGDs have also been reported in boys with hypospadias, in men with poor semen quality, and in men with testicular cancer.
    Study design, size, duration: A prospective descriptive cohort study was performed using data from consecutively selected boys with cryptorchidism (n = 169) operated in a single center over a period of 3 years (September 2019 to October 2022).
    Participants/materials, setting, methods: AGD was measured in 169 infant boys, at 3 to 26 months of age, during anesthesia with a vernier caliper measuring the distance from the anus to the base of the scrotum (AGDAS) and from the anus to the anterior base of the penis (AGDAP) in two body positions according to the methods by 'The Infant Development and the Environment Study' (TIDES) and 'Cambridge Baby Growth Study', resulting in four mean values per patient (TIDES AGDAS/AP and Cambridge AGDAS/AP). Normal values for AGD by age were set by our hospital Department of Growth and Reproduction based on a large cohort of healthy infant boys (n = 1940). Testicular biopsies were performed at orchidopexy as a clinical routine. The germ cell number (G/T) and type Ad spermatogonia number (AdS/T) per cross-sectional tubule of at least 100 and 250 tubules, respectively were measured and related to normal samples. Blood samples were obtained by venipuncture for measuring serum LH, FSH, and inhibin B. They were analyzed in our hospital Department of Growth and Reproduction where the normal reference was also established. Correlations between the four mean AGD measurements for each boy were evaluated by Spearman rank correlation analyses. The AGD measurement of every boy was transferred to the multiple of the median (MoM) of the normal AGD for age and named MoM AGD.
    Main results and the role of chance: There were 104 boysoperated for unilateral, and 47 boys operated for bilateral, undescended testes, whereas 18 boys had vanished testis including one boy with bilateral vanished testes. Only 6% of cases with vanished testes had a MoM AGD higher than the normal median compared to 32% with undescended testes (P < 0.05). MoM AGD increased with the age at surgery for boys with vanished testis (Spearman r = 0.44), but not for boys with undescended testes (Spearman r = 0.14). Boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism (P < 0.005) and (P < 0.000001).
    Limitations, reasons for caution: Although being the largest published material of AGD measurements of infant boys with cryptorchidism, one limitation of this study covers the quite small number of patients in the different groups, which may decrease the statistical power. Another limitation involves the sparse normal reference material on G/T and AdS/T. Finally, there are currently no longitudinal studies evaluating AGD from birth to adulthood and evaluating childhood AGD in relation to fertility outcome. Our study is hypothesis generating and therefore the interpretation of the results should be regarded as exploratory rather than reaching definite conclusions.
    Wider implications of the findings: The study findings are in agreement with literature as the total included group of boys with cryptorchidism exhibited shorter than normal AGDs. However, new insights were demonstrated. Boys with vanished testis had shorter AGDs compared to unaffected boys and to boys with undescended testes. This finding challenges the current concept of AGD being determined in 'the masculinization programming window' in Week 8 to 14 of gestation. Furthermore, boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism, suggesting that the lack of fetal androgen in hypogonadotropic hypogonadism is not that significant.
    Study funding/competing interest(s): No external funding was used and no competing interests are declared.
    Trial registration number: The trial was not registered in an ICMJE-recognized trial registry.
    MeSH term(s) Male ; Pregnancy ; Infant ; Female ; Child ; Humans ; Cryptorchidism/surgery ; Testicular Neoplasms ; Androgens ; Semen Analysis ; Cohort Studies ; Cross-Sectional Studies ; Prospective Studies ; Hypogonadism ; Gonadal Dysgenesis, 46,XY ; Testis/abnormalities
    Chemical Substances Androgens
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 632776-x
    ISSN 1460-2350 ; 0268-1161 ; 1477-741X
    ISSN (online) 1460-2350
    ISSN 0268-1161 ; 1477-741X
    DOI 10.1093/humrep/deae025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Inhibin-B Level at Orchidopexy and Follow-up of 280 Boys With Non-syndromic Unilateral Cryptorchid Testes.

    Hildorf, Simone / Cortes, Dina / Clasen-Linde, Erik / Hildorf, Andrea / Thorup, Jorgen

    Journal of pediatric surgery

    2023  Volume 58, Issue 11, Page(s) 2233–2237

    Abstract: Purpose: An impaired germ cell number per tubular cross-section (G/T) at orchidopexy indicates a high risk of infertility. A recent study in boys with bilateral cryptorchidism showed a very high predictive value for a low serum inhibin-B level, ... ...

    Abstract Purpose: An impaired germ cell number per tubular cross-section (G/T) at orchidopexy indicates a high risk of infertility. A recent study in boys with bilateral cryptorchidism showed a very high predictive value for a low serum inhibin-B level, indicating bilateral impaired G/T. Several other studies have shown a fairly strong correlation between inhibin-B and G/T. We aimed to evaluate if inhibin-B levels at orchidopexy improved at follow-up in boys with unilateral cryptorchidism.
    Methods: We included 280 boys with unilateral non-syndromic cryptorchidism at the median age of 1 year (4 months-9 years) who underwent orchidopexy. They were evaluated for serum FSH, LH and inhibin-B levels at surgery and at follow-up (median 16 months later), including multiple of the median (MoM) estimations of inhibin-B due to the age dependency of normal levels.
    Results: The inhibin-B MoM score improved significantly at follow-up. At orchidopexy, 59 (21%) boys had inhibin-B levels below the normal 2.5-percentile indicating impaired G/T bilaterally. At follow-up, 36% of the boys still had low inhibin-B. At orchidopexy, 221 (79%) boys had inhibin-B levels above normal 2.5-percentile and only 5% had low inhibin-B levels at follow-up. The risk of low inhibin-B levels at follow-up was significantly different between the two groups (p < 0.0001). At follow-up, totally, 32 (11%) boys had low inhibin-B levels, hereof only 3 patients with increased FSH.
    Conclusions: Orchidopexy benefits the fertility potential. About 10% of boys with unilateral non-syndromic cryptorchidism may have a bilateral testicular disease reducing their fertility potential. Insufficient gonadotropin stimulation may possibly be the cause.
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80165-3
    ISSN 1531-5037 ; 0022-3468
    ISSN (online) 1531-5037
    ISSN 0022-3468
    DOI 10.1016/j.jpedsurg.2023.07.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Extranodal NK/T-cell lymphoma, nasal type, with extranasal presentation - a case report and a review of the literature.

    Akbar, Momena / Clasen-Linde, Erik / Specht, Lena

    Acta oncologica (Stockholm, Sweden)

    2020  Volume 59, Issue 12, Page(s) 1480–1487

    Abstract: Background: Extranodal NK/T-cell lymphoma (ENKTCL), nasal type is a very rare and aggressive non-Hodgkin lymphoma. Most commonly it occurs in the upper aerodigestive tract. But, it can also manifest at locations such as the skin, soft tissue, ... ...

    Abstract Background: Extranodal NK/T-cell lymphoma (ENKTCL), nasal type is a very rare and aggressive non-Hodgkin lymphoma. Most commonly it occurs in the upper aerodigestive tract. But, it can also manifest at locations such as the skin, soft tissue, gastrointestinal tract (GI), lungs, testis, etc. These locations are designated as extranasal ENKTCL. The patients with the latter have often more adverse clinical features and poorer survival rate compared with nasal sites. We present a case of an 83-year-old patient with a primary ENKTCL, nasal type, with extranasal presentation in the right upper eyelid.
    Material and methods: Materials for the literature review was obtained by a comprehensive search on PubMed, which yielded 82 eligible cases with extranasal ENKTCL.
    Results: Sixty-eight cases (83 %) were localized as primary ENKTCL in the lungs (17), central nervous system (CNS) (14), testis (11), GI-tract (7), skin (6), orbit and intraocular tissue (4), pancreas (2), adrenal gland (2), breast (1), etc. 14 cases (17 %) presented as extended or disseminated diseases involving exclusively organs outside the upper aerodigestive tract. There was no systematic pattern of organ involvement in the extended/disseminated ENKTCL. 63 % of the patient with localized extranasal ENKTCL and about 50% of patients with extended/disseminated disease were reported to have died of the disease. Treatment strategies varied with no preferred option. Among the used treatment options were chemotherapy, radiotherapy, surgery, stem cell transplantation alone or in different combinations.
    Conclusion: ENKTCL is a highly aggressive disease which may present in extranasal areas. Although the tumors respond to both chemotherapy and radiotherapy, durable complete remissions are very rare.
    MeSH term(s) Aged, 80 and over ; Humans ; Lymphoma, Extranodal NK-T-Cell/diagnosis ; Lymphoma, Extranodal NK-T-Cell/therapy ; Male ; Nose Neoplasms/therapy ; Prognosis ; Survival Rate
    Language English
    Publishing date 2020-07-20
    Publishing country England
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 896449-x
    ISSN 1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
    ISSN (online) 1651-226X
    ISSN 0349-652X ; 0284-186X ; 1100-1704
    DOI 10.1080/0284186X.2020.1795250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The positive predictive value of using fsh and Inhibin-B serum levels to diagnose gonadotropin insufficiency in bilateral cryptorchid boys is high.

    Hildorf, Simone E / Clasen-Linde, Erik / Cortes, Dina / Fossum, Magdalena / Thorup, Jorgen

    Journal of pediatric urology

    2022  Volume 18, Issue 6, Page(s) 844.e1–844.e7

    Abstract: Aim of study: Despite early surgery, many boys with bilateral cryptorchidism at surgery have a reduced number of germ cells per tubular cross-section (G/T) in testicular biopsies and/or low inhibin-B with no elevated follicle-stimulating hormone (FSH) ... ...

    Abstract Aim of study: Despite early surgery, many boys with bilateral cryptorchidism at surgery have a reduced number of germ cells per tubular cross-section (G/T) in testicular biopsies and/or low inhibin-B with no elevated follicle-stimulating hormone (FSH) as expected based on a normal gonadotropin feed-back mechanism. Such boys have a high risk of later infertility because of insufficient gonadotropin stimulation and may benefit from adjuvant hormonal treatment. Testicular biopsies are not always wanted or accepted. The study aim was to investigate the value of a low inhibin-B and normal FSH to identify patients that might benefit from adjuvant hormonal treatment avoiding the need for testicular biopsy.
    Methods: A series of boys with cryptorchidism were evaluated with serum levels of inhibin-B and FSH in relation to G/T in testicular biopsies, which were compared to previously published age-matched normal control values.
    Results: A total of 365 boys who underwent bilateral orchidopexy between 0.4 and 7.8 (median: 2) years of age were included. Twenty-seven (7%) patients had increased FSH and low G/T, whereas 11 of these also had low inhibin-B indicating hypergonadotropic hypogonadism. Moreover, 85 (23%) patients between 0.75 and 7.5 (median: 2) years of age had both low G/T (median: 0.3) and low inhibin-B (median: 56 pg/ml) but normal FSH (median: 0.6 U/l) indicating a gonadotropin insufficiency. Three patients with normal FSH and low inhibin B had normal G/T.
    Discussion: Our study shows that if surgeons prefer to avoid testicular biopsies and only wish to rely on hormonal parameters (low inhibin-B and normal FSH) in order to diagnose a gonadotropin insufficiency as the cause of hypogonadism, they will identify only about 30% of such cases and overlook about 70% of patients sharing the same endocrinopathy. In addition, if surgeons treat patients for gonadotropin insufficiency only based on low inhibin-B and normal FSH they will solely treat patients with gonadotropin insufficiency and would not overtreat patients.
    Conclusion: Adjuvant hormonal treatment was indicated by a gonadotropin insufficiency discerned in 23% of boys with bilateral cryptorchidism. Without histology, the clinicians are left with more difficult clinical judgments to identify patients for adjuvant hormonal treatment. The positive predictive value of low inhibin-B and normal FSH corroborated by low G/T was 0.97 (85/85 + 3), but the sensitivity was low (0.30).
    MeSH term(s) Male ; Humans ; Cryptorchidism/complications ; Cryptorchidism/diagnosis ; Cryptorchidism/surgery ; Predictive Value of Tests ; Follicle Stimulating Hormone ; Inhibins ; Gonadotropins/therapeutic use ; Testis/surgery
    Chemical Substances inhibin B ; Follicle Stimulating Hormone (9002-68-0) ; Inhibins (57285-09-3) ; Gonadotropins
    Language English
    Publishing date 2022-11-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2237683-5
    ISSN 1873-4898 ; 1477-5131
    ISSN (online) 1873-4898
    ISSN 1477-5131
    DOI 10.1016/j.jpurol.2022.10.031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Primary malignant melanoma of the urethra in a patient with rheumatoid arthritis treated with methotrexate.

    Hansen, Margrethe Foss / Abel, Ivan / Clasen-Linde, Erik

    BMJ case reports

    2019  Volume 12, Issue 4

    Abstract: We report a case of a 79-year-old woman with urinary incontinence who presented at a urogynaecology appointment. Her medical history included rheumatoid arthritis (RA) treated with methotrexate (MXT) for 22 years. A polypoidal lesion was protruding from ... ...

    Abstract We report a case of a 79-year-old woman with urinary incontinence who presented at a urogynaecology appointment. Her medical history included rheumatoid arthritis (RA) treated with methotrexate (MXT) for 22 years. A polypoidal lesion was protruding from the meatus urethrae. The histoimmunocytology confirmed a primary superficial spreading malignant melanoma. The tumour was extensively excised, but 8 months later, due to a lymphatic nodal swelling, a positron emission tomography/CT was performed showing a process suspicious of malignant melanoma and multiple distant metastasis. The subsequent treatment was palliative and 1 year later, the patient died. The aetiology of malignant melanomas in the urethra is poorly understood. There is consistent evidence that RA is associated with a number of cancers, but it remains controversial whether this risk is increased with MXT. This case emphasises the importance of gynaecological examination even in patients with only weak symptoms from the pelvic region, especially in patients undergoing immunosuppressive treatment.
    MeSH term(s) Aged ; Antirheumatic Agents/adverse effects ; Arthritis, Rheumatoid/drug therapy ; Female ; Humans ; Melanoma/chemically induced ; Methotrexate/adverse effects ; Urethra/drug effects ; Urethral Neoplasms/chemically induced
    Chemical Substances Antirheumatic Agents ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2019-04-03
    Publishing country England
    Document type Case Reports ; Journal Article
    ISSN 1757-790X
    ISSN (online) 1757-790X
    DOI 10.1136/bcr-2018-228033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Serial Inhibin B Measurements in Boys with Congenital Monorchism Indicate Compensatory Testicular Hypertrophy in Early Infancy.

    Hildorf, Simone / Clasen-Linde, Erik / Cortes, Dina / Fossum, Magdalena / Thorup, Jorgen

    European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie

    2021  Volume 32, Issue 1, Page(s) 34–41

    Abstract: Aim:  Congenital monorchism is considered a condition in which an initially normal testis has existed but subsequently atrophied and disappeared due to a third trimester catastrophe (presumably torsion). Since inhibin B concentrations appear related to ... ...

    Abstract Aim:  Congenital monorchism is considered a condition in which an initially normal testis has existed but subsequently atrophied and disappeared due to a third trimester catastrophe (presumably torsion). Since inhibin B concentrations appear related to Sertoli and germ cells number, we evaluated pre- and postoperative inhibin B of boys with congenital monorchism to determine whether the well-known hypertrophy of the contralateral testis was reflected in inhibin B concentrations.
    Materials and methods:  Twenty-seven boys consecutively diagnosed with congenital monorchism (median age 12 months) underwent follow-up with reproductive hormones 1 year postoperatively (median age 25 months). The results were compared with inhibin B of 225 boys with congenital nonsyndromic unilateral cryptorchidism, by converting values to multiple of the median (MoM) for age in normal boys.
    Results:  Ten boys (37%) had blind-ending vessels and ductus deferens (vanished testis) and the remaining (63%) had testicular remnants. At the time of diagnostic procedure, monorchid boys did not have significantly lower inhibin B (median 114, range 20-208) than unilateral cryptorchid boys (136, 47-393) (
    Conclusion:  Generally, inhibin B MoM values were normalized during follow-up in boys with congenital monorchism, reflecting compensatory hypertrophy within the first 2.5 years of life. The compensatory capacity to increase was better in monorchism than in unilateral cryptorchidism.
    MeSH term(s) Child, Preschool ; Cryptorchidism/diagnosis ; Cryptorchidism/surgery ; Humans ; Hypertrophy ; Infant ; Inhibins ; Male ; Testis/surgery
    Chemical Substances inhibin B ; Inhibins (57285-09-3)
    Language English
    Publishing date 2021-11-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1065043-x
    ISSN 1439-359X ; 0939-7248 ; 0939-6764 ; 0930-7249
    ISSN (online) 1439-359X
    ISSN 0939-7248 ; 0939-6764 ; 0930-7249
    DOI 10.1055/s-0041-1739417
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The impact of early and successful orchidopexy on hormonal follow-up for 208 boys with bilateral non-syndromic cryptorchidism.

    Hildorf, Simone / Cortes, Dina / Clasen-Linde, Erik / Fossum, Magdalena / Thorup, Jorgen

    Pediatric surgery international

    2021  Volume 37, Issue 3, Page(s) 339–345

    Abstract: Purpose: Inhibin-B is produced by Sertoli cells and decreased values might be associated with impaired fertility potential. The aim of the study was to evaluate the impact of bilateral orchidopexy on serum inhibin-B and follicle-stimulating hormone (FSH) ...

    Abstract Purpose: Inhibin-B is produced by Sertoli cells and decreased values might be associated with impaired fertility potential. The aim of the study was to evaluate the impact of bilateral orchidopexy on serum inhibin-B and follicle-stimulating hormone (FSH).
    Methods: A cohort study including 208 bilateral cryptorchid boys (median age: 1.7 year) was evaluated with serum inhibin-B and FSH in relation to histological parameters. Based on the fertility potential, the boys were divided into three subgroups. At follow-up (median age: 2.7 years) the boys were evaluated with FSH and in case of inhibin-B using multiple of the median (MoM).
    Results: Inhibin-B MoM improved significantly at follow-up. In 32 boys with high FSH at orchidopexy 63% normalized FSH and 59% increased MoM inhibin-B, but 31% had impaired inhibin-B at follow-up. In 105 boys with transient hypogonadotropic hypogonadism, 52% increased inhibin-B MoM but 31% had impaired inhibin-B at follow-up. In 71 boys with normal FSH, inhibin-B, and G/T, 54% increased inhibin-B MoM and 15% had impaired inhibin-B at follow-up. The effect of the surgery was best in patients younger than 1 year.
    Conclusion: Orchidopexy, especially before 1 year of age, improves the fertility potential in bilateral cryptorchidism. At follow-up, 26% (54/208) had a risk of infertility based on inhibin-B.
    MeSH term(s) Child, Preschool ; Cohort Studies ; Cryptorchidism/surgery ; Fertility ; Follicle Stimulating Hormone/blood ; Follow-Up Studies ; Humans ; Infant ; Inhibins ; Male ; Orchiopexy
    Chemical Substances inhibin B ; Inhibins (57285-09-3) ; Follicle Stimulating Hormone (9002-68-0)
    Language English
    Publishing date 2021-01-09
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 632773-4
    ISSN 1437-9813 ; 0179-0358
    ISSN (online) 1437-9813
    ISSN 0179-0358
    DOI 10.1007/s00383-020-04820-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: During infancy low levels of follicle-stimulating hormone may result in high rate of germ cell apoptosis.

    Hildorf, Simone / Cortes, Dina / Thorup, Jørgen / Clasen-Linde, Erik / Hutson, John / Li, Ruili

    Journal of pediatric surgery

    2021  Volume 56, Issue 12, Page(s) 2399–2406

    Abstract: Purpose: It has been suggested that follicle-stimulating hormone (FSH) plays a role in preventing germ cell apoptosis. We aimed to compare apoptotic rate of boys with cryptorchidism having different levels of FSH in order to investigate its role in ... ...

    Abstract Purpose: It has been suggested that follicle-stimulating hormone (FSH) plays a role in preventing germ cell apoptosis. We aimed to compare apoptotic rate of boys with cryptorchidism having different levels of FSH in order to investigate its role in apoptosis.
    Methods: Hormonal profiles and testicular biopsies from 30 boys with unilateral cryptorchidism (age range: 4-14 months) were included. Based on FSH level, the boys were grouped into three (3 × 10) having high (>97.5percentile), low (<2.5percentile), or within normal range. Sections underwent immunohistochemical staining to analyze the number of germ cells and type A dark spermatogonia per cross-sectional tubule. One section was co-stained with immunofluorescent antibodies against an apoptotic marker (cleaved caspase-3), proliferation marker (Ki67), Sertoli cell marker (anti-Müllerian hormone) and processed by confocal imaging for analysis. Germ cell apoptosis was calculated as the apoptosis index (percentage caspase-3+ germ cells/total germ cell number).
    Results: Fifty percent (5/10) of the boys with low FSH had an apoptosis index above 90% compared with 15% (3/20) of the boys with normal or high FSH (p = 0.04). Caspase-3+ germ cells were most likely to be located on the basement membrane (p<0.05).
    Conclusion: Our findings lead to trends proposing that FSH may play a role in preventing apoptosis.
    Type of study: Prognosis Study LEVEL OF EVIDENCE: III.
    MeSH term(s) Apoptosis ; Cross-Sectional Studies ; Cryptorchidism ; Follicle Stimulating Hormone ; Humans ; Infant ; Male ; Sertoli Cells ; Spermatogonia ; Testis
    Chemical Substances Follicle Stimulating Hormone (9002-68-0)
    Language English
    Publishing date 2021-02-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80165-3
    ISSN 1531-5037 ; 0022-3468
    ISSN (online) 1531-5037
    ISSN 0022-3468
    DOI 10.1016/j.jpedsurg.2021.02.012
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  9. Article ; Online: Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features.

    Eriksen, Patrick R G / de Groot, Fleur / Clasen-Linde, Erik / de Nully Brown, Peter / de Groen, Ruben / Melchior, Linea C / Maier, Andrea D / Minderman, Marthe / Vermaat, Joost S P / von Buchwald, Christian / Pals, Steven T / Heegaard, Steffen

    Blood advances

    2024  Volume 8, Issue 8, Page(s) 1946–1957

    Abstract: Abstract: Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare lymphoma with a variable prognosis and a unique relapse/dissemination pattern involving the central nervous system and skin. The underlying molecular mechanisms leading to ... ...

    Abstract Abstract: Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare lymphoma with a variable prognosis and a unique relapse/dissemination pattern involving the central nervous system and skin. The underlying molecular mechanisms leading to this heterogeneity and progression pattern remain uncharted, hampering patient-tailored treatment. To investigate associated mechanisms, we analyzed clinical data and used immunohistochemistry, gene-expression profiling, cytogenetics, and next-generation sequencing in a cohort of 117 patients with PSDLBCL. The distribution in cell-of-origin (COO) was 68 (58%) activated B-cell (ABC), 44 (38%) germinal center B-cell (GCB), and 5 (4%) unclassifiable. COO was significantly associated with progression-free survival (PFS) and lymphoma-specific mortality (LSM) in both the overall cohort (5-year PFS: ABC, 43% vs GCB, 73%; LSM: ABC, 45% vs GCB, 14%) and in the subgroup of patients receiving immunochemotherapy (5-year PFS: ABC, 55% vs GCB, 85%; LSM: ABC, 28% vs GCB, 0%). ABC lymphomas were mainly MCD class, showing a high prevalence of MYD88 (74%) and CD79B (35%) mutations compared with GCB lymphomas (MYD88 23%; CD79B 10%) (P < .01). The ABC subtype frequently displayed cMYC/BCL2 coexpression (76% vs 18% GCB; P < .001) and HLA-II loss (48% vs 10% GCB; P < .001). PD-L1 expression and copy-number alterations were rare. All lymphomas were Epstein-Barr virus-negative. Our data suggest molecular profiling as a potent tool for detecting prognostic subgroups in PSDLBCL, exposing links to known relapse/dissemination sites. The ABC subgroup's MCD genetic features, shared with lymphomas at other nonprofessional lymphoid sites, make them potential candidates for targeted B-cell and toll-like receptor signaling therapy.
    MeSH term(s) Humans ; Epstein-Barr Virus Infections ; Myeloid Differentiation Factor 88/metabolism ; Herpesvirus 4, Human/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Recurrence
    Chemical Substances Myeloid Differentiation Factor 88
    Language English
    Publishing date 2024-02-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023011517
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  10. Article ; Online: Pearls and Pitfalls in Interpretation of 68Ga-DOTATOC PET Imaging.

    Bashir, Asma / Broholm, Helle / Clasen-Linde, Erik / Vestergaard, Mark B / Law, Ian

    Clinical nuclear medicine

    2020  Volume 45, Issue 6, Page(s) e279–e280

    Abstract: DOTA-D-Phe-Tyr-octreotide labeled with Ga (Ga-DOTATOC) is the commonly used PET tracer for imaging meningioma because of its high affinity to somatostatin receptor subtype 2 (SSTR2) and an established imaging modality for planning radiation and ... ...

    Abstract DOTA-D-Phe-Tyr-octreotide labeled with Ga (Ga-DOTATOC) is the commonly used PET tracer for imaging meningioma because of its high affinity to somatostatin receptor subtype 2 (SSTR2) and an established imaging modality for planning radiation and radionuclide therapy. However, SSTR2 is not an exclusive marker for meningioma, and not all meningiomas express high levels of SSTR2. The SSTR2 expression has been reported in other intracranial tumors, for example, glioma, pituitary adenoma, medullablastoma, primitive neuroectodermal tumors, and hemangioblastoma leading to a significant risk of misinterpretation of PET/CT findings. We present 2 cases with similar Ga-DOTATOC uptakes in 2 distinct etiologies, for example, cerebral lymphoma and meningioma.
    MeSH term(s) Aged ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/metabolism ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Male ; Meningeal Neoplasms/diagnostic imaging ; Meningeal Neoplasms/metabolism ; Meningioma/diagnostic imaging ; Meningioma/metabolism ; Middle Aged ; Octreotide/analogs & derivatives ; Octreotide/metabolism ; Organometallic Compounds/metabolism ; Positron Emission Tomography Computed Tomography ; Receptors, Somatostatin/metabolism
    Chemical Substances Ga(III)-DOTATOC ; Organometallic Compounds ; Receptors, Somatostatin ; somatostatin receptor 2 (D73QL0OMU2) ; Octreotide (RWM8CCW8GP)
    Language English
    Publishing date 2020-04-23
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 197628-x
    ISSN 1536-0229 ; 0363-9762
    ISSN (online) 1536-0229
    ISSN 0363-9762
    DOI 10.1097/RLU.0000000000003012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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