Cystic Crypt Changes in Midgestational Human Vermiform Appendix: An Unrecognized Transient Histologic Feature.

INTRODUCTION: Lewis and Huff briefly described the presence of "microcystic cryptitis" in some of fetal vermiform appendices (VA) at autopsy. We further characterized these crypt changes (CC), their timing of occurrence, and tested their association with infection/inflammatory conditions. METHODS: Hematoxylin and eosin-stained slides of 345 VA were evaluated for the presence or absence of CC and their different morphologies. Autopsy reports were reviewed for evidence of amniotic fluid or fetal systemic infection and placental inflammatory conditions. RESULTS: Crypt dilatation with or without irregularity of the lumen, crypt dilatation with semiattenuated epithelium, intraluminal apoptotic debris and inflammatory cells, especially eosinophils, and foci of swirled spindled cells with calcifications or multinucleated giant cells were observed, either alone or in combination, in at least 58.5% (202/345) of the VA. CC began to appear at 17 weeks, peaked at 20 to 25 weeks (with up to 82% of VA exhibiting CC during this time), and followed by a steady decline beyond 28 weeks gestation. χ2 test of independence showed no significant association (P = .435; >0.05) between the presence and absence of CC and infection status of the fetus or placenta. CONCLUSION: The underrecognized CC of the developing fetal vermiform appendix (VA) showed distinct temporal pattern of occurrence and did not seem to be affected by the presence or absence of infection, which so far favored their being a part of the normal gut developmental process.

Cryptorchidism: diagnosis, treatment, and long-term prognosis.

Cryptorchidism is a common anomaly treated by every pediatric urologist. The etiology is multifactorial and includes hormonal and molecular factors. Diagnostic abilities may be enhanced by radiologic advances. Hormonal and surgical treatment modalities are discussed herein, as well as the identification and prevention of long-term sequelae.

Tracheal anomalies in Pfeiffer syndrome.

OBJECTIVE: To determine the types and frequency of airway anomalies in patients with Pfeiffer syndrome. DESIGN: Retrospective case series. SETTING: Academic tertiary care pediatric hospital. PARTICIPANTS: Eleven patients with Pfeiffer syndrome, 6 of whom were severely affected, were identified. All were included in the study. MAIN OUTCOME MEASURES: Presence of tracheal anomalies, need for tracheotomy, and length of life. RESULTS: The 6 severely affected patients had mutations in genes that code for fibroblast growth factor receptor 2 (S351C [3 patients]; C342S [2 patients]; and W290C [1 patient]). Five of these patients were diagnosed during bronchoscopy or tracheotomy as having a congenital tracheal cartilaginous sleeve. In 1 patient, supportive care was withdrawn at 2 weeks of life, and the patient died. The remaining 5 patients required tracheotomy because of severe upper airway obstruction. Three of these patients died (at ages 9 months and 7 and 15 years). Two are still alive at ages 23 and 18 months. CONCLUSIONS: Patients with Pfeiffer syndrome manifest significant airway pathologic conditions. Upper airway obstruction is related to midface hypoplasia and secondary nasal obstruction. Tracheal anomalies have been infrequently reported.

Craniosynostosis with tracheal sleeve: a patient with Pfeiffer syndrome, tracheal sleeve and additional malformations in whom an FGFR2 mutation was found.

We discuss a patient with Pfeiffer syndrome who had a tracheal sleeve and an FGFR2 mutation. In the light of our findings, and previous reports of patients with craniosynostosis that also reported similar mutations, we suggest that genomic screening for FGFR2 may be useful in cases with negative FGFR2 mutation testing.

Cryptorchid testis histopathology in myelomeningocele patients.

PURPOSE: Cryptorchidism occurs in 25% of boys with myelomeningocele (MMC) compared to 3% of the general population. Testicular biopsy histopathology correlates with future sperm counts. We studied testicular histology in boys with cryptorchidism and MMC to investigate if the MMC influences histological findings. MATERIALS AND METHODS: The study group consisted of six patients with MMC and undescended testis (UDT) who underwent orchiopexy and bilateral testis biopsy. Twelve testicular biopsies from six patients were compared to 40 biopsies from 20 UDT-only controls. Total germ cell count per tubule (TGC/T) and the percentage of adult dark spermatogonia (%Ad) in undescended and contralateral descended testes from the patients were compared with controls. RESULTS: In the study group, two had total absence of germ cells (TGC/T=0) and three had severely reduced germ cells (TGC/T<0.2). Four had total absence of Ad spermatogonia and the remaining two had severely reduced Ad spermatogonia (%Ad=5). The mean TGC/T and %Ad in patients with UDT and MMC were conspicuously lower than controls. The differences did not reach statistical significance (P=0.09-0.29). CONCLUSION: These results suggest that patients with both MMC and UDT have a more severe reduction in total number and more severely delayed maturation of germ cells than do patients with UDT alone. With only six patients in this study, there was not the power to detect statistical significance. In addition to the reproductive problems due to erection and ejaculatory dysfunction in patients with MMC, this severe testicular histopathology may increase the risk of subfertility.

Testicular microlithiasis and antisperm antibodies following testicular biopsy in boys with cryptorchidism.

PURPOSE: Testicular biopsy (TBx) performed during orchiopexy in boys with cryptorchidism can help to predict future semen analyses and possibly identify patients at risk for testicular cancer. It has been theorized that TBx can be detrimental to the long-term health of the testis. We examined testicular microlithiasis (TM) and antisperm antibody (ASA) production in cryptorchid TBx. MATERIALS AND METHODS: A total of 112 males underwent fertility evaluation. These patients had previously undergone orchiopexy and bilateral TBx (mean age 8.6 years) for unilateral or bilateral undescended testis. At a mean age of 19.6 years all patients underwent physical examination and scrotal ultrasound for evaluation of testis size, echotexture and abnormalities. Of 112 patients 57 also underwent direct Immunobead(R) assay with positive controls. Moving sperm free and/or bound to IgG bead complex were counted in the preparation. RESULTS: A total of 29 patients had bilateral and 83 had unilateral undescended testis. Of the 112 patients 26 were black and 86 were white. Four black patients (15.4%) and 4 white patients (4.7%) had testicular microlithiasis. Three patients had bilateral and 5 had unilateral diffuse TM. No tunica albuginea scars or testis masses were noted. In the 57 patients who underwent direct Immunobead assay no semen sample demonstrated evidence of forming bead-sperm complex, ie none had direct ASA. CONCLUSIONS: No patient exhibited evidence of direct ASA. Prepubertal open TBx does not increase the rate of TM. We found no evidence of additive testicular damage associated with TBx at the time of orchiopexy.

Testis histopathology in boys with cryptorchidism correlates with future fertility potential.

PURPOSE: We studied the ability of testis biopsy to predict eventual fertility potential. MATERIALS AND METHODS: A total of 25 patients with unilateral undescended testis and 11 with bilateral undescended testes who previously underwent orchiopexy at a median age of 9 years were followed until after age 18 years. Semen analysis, testicular volume, follicle-stimulating hormone, luteinizing hormone, testosterone and inhibin B were compared to previously obtained biopsies of each testis. Biopsies were graded as mild, moderate or severe histology based on published data for normal and undescended testis histology. RESULTS: Patients with unilateral undescended testis and moderate histology were more likely to have a sperm density of greater than 20 million per cc than those with severe histology (p = 0.006), although no difference in hormonal parameters was noted. Patients with bilateral undescended testes and moderate histology were more likely to have normal follicle-stimulating hormone and inhibin B than those with severe histology (p = 0.05 and 0.002, respectively), although no difference in semen analysis was observed. Overall 7 of the 9 patients with bilateral undescended testes had less than 20 million sperm per cc. CONCLUSIONS: Testis biopsy provides useful prognostic information about semen analysis in patients with unilateral undescended testis. In the 9 patients with bilateral undescended testes testis biopsy divided them into normal and abnormal groups in terms of hormonal parameters. Testis biopsy was not able to provide additional prognostic information on semen analysis in patients with bilateral undescended testes since they were uniformly poor.

Juvenile granulosa cell tumor of the testis:: contemporary clinical management and pathological diagnosis.

PURPOSE: Juvenile granulosa cell tumor (JGCT) of the testis is a rarely diagnosed subset of testicular stromal tumors. Although this variant of testicular stromal tumor is predominantly a benign entity in prepubertal patients, limited experience precludes a complete understanding of its clinical presentation and pathological diagnosis. MATERIALS AND METHODS: We reviewed all cases of testicular tumors at Children's Hospital of Philadelphia between 1976 and 2002 in males younger than 18 years. We specifically reviewed our experience with JGCT in terms of presentation, surgical treatment and long-term outcome. We also reviewed the microscopic findings and histochemical techniques used to confirm the diagnosis. RESULTS: We identified 77 tumors during the defined interval, of which 3 (3.9%) were JGCTs. All 3 patients with JGCT were first noted to have a testis mass soon after birth. All presented with a firm, unilateral testicular mass. Ultrasonographic findings were consistent with a complex, multiseptated, hypoechoic mass. Two of the 3 patients underwent radical orchiectomy. Testis sparing mass excision was performed in 1 patient. Grossly the tumors were partially cystic masses. Histologically positive immunostaining with inhibin-alpha and negative staining for alpha-fetoprotein (AFP) reliably differentiated JGCTs from yolk sac tumors. At a mean followup of 8.5 years (range 5 to 14) no metastases or local tumor recurrences have been diagnosed. CONCLUSIONS: To our knowledge we report the first case of testis sparing enucleation of a JGCT with a 5-year recurrence-free followup. Testis sparing enucleation is now our procedure of choice for tumors in neonates and prepubertal children with serum AFP in the normal range for age. JGCT should be suspected in neonates presenting at birth with a complex, cystic mass of the testis. Positive immunostaining for inhibin-alpha and a lack of AFP staining have consistently corroborated the pathological diagnosis in our experience and they should be applied for pediatric testis tumors that may mimic yolk sac tumor pathology.

Experience with testis sparing surgery for testicular teratoma.

PURPOSE: Testicular teratoma is a rare neoplasm affecting the pediatric population and has classically been reported to be the second most common testis tumor in children behind yolk sac tumors. Testicular teratomas are benign and partial orchiectomy may be considered. We describe our single institution experience with testicular teratoma and definitive treatment with testis preserving surgery. MATERIALS AND METHODS: We reviewed the pathology records at our institution for all testicular and paratesticular tumors diagnosed between 1976 and November 2002 in males younger than 18 years. We specifically examined the prepubertal incidence of teratoma, including epidermoid cysts, and our experience with testis preserving surgery. Preoperative and postoperative ultrasonography images were used to calculate the atrophy index following surgery. Patients were contacted for long-term followup. RESULTS: Of 77 primary testicular and paratesticular tumors 38 were diagnosed in prepubertal boys (age younger than 13 years) including 11 mature teratomas and 5 epidermoid cysts. Mean patient age at treatment was 34.4 months (range 4 months to 10 years). All boys presented with a painless scrotal mass, cystic foci within an intratesticular mass on ultrasound and a normal alpha-fetoprotein level. Of the 16 boys with benign teratomas 13 (81%) were treated with a testis sparing procedure. At a mean 7-year followup no patient has presented with recurrent tumor in the ipsilateral or contralateral testicle. Postoperative physical examination and scrotal ultrasound were obtained in 9 patients at a median followup of 10.2 months, and there was no evidence of testicular atrophy or persistent discomfort. CONCLUSIONS: Unlike previously published series based on tumor registries, benign teratoma was the most common pediatric testicular tumor treated at our institution. Our single institution experience with testis preservation and long-term followup confirms the role and safety of this technique. Testis sparing surgery remains our technique of choice for testicular teratoma.

Prepubertal testis tumors: actual prevalence rate of histological types.

PURPOSE: Tumor registries, urological textbooks and literature surveys all assert that yolk sac tumors are the most common primary testicular tumors in boys 12 years and younger. In contrast, several individual institutions have reported that benign tumors are more common than malignant tumors. To clarify these discordant findings, we surveyed the primary pathology records from 4 major pediatric centers. MATERIALS AND METHODS: The pathology records of the contributing centers were culled for primary testicular masses in boys 12 years and younger. Older boys and those with either paratesticular tumors or leukemia were excluded. The prevalence of each histological subtype was calculated from the pooled cases. RESULTS: A total of 98 patients met our criteria. Only 15% had yolk sac tumors. Teratomas comprised 48% of the tumors (mature 44%, immature 4%). Epidermoid cysts were found in another 14% of patients. Gonadal stromal cell tumors represented 13% of the total, divided among granulosa cell (5%), Leydig cell (4%), Sertoli cell (3%) and mixed gonadal stromal cell (1%). Other pathology, including cystic dysplasia (2), lymphoma (4), inflammatory pseudotumor (1) and gonadoblastoma (2), made up 9% of the total number of cases. CONCLUSIONS: We found that benign lesions represent the majority of primary testis tumors (74%), with the most common histological type being teratoma (48%). The reported high prevalence rates of prepubertal yolk sac tumors probably results from a reporting bias, since benign tumors are less likely to be submitted to tumor registries. Therefore, the primary operative approach to the majority of testis tumors in boys 12 years and younger should entail testis sparing surgery. Orchiectomy should be reserved for histologically confirmed malignancy based on increased preoperative alpha-fetoprotein and/or frozen section analysis of the tumor.

The ascending testis and the testis undescended since birth share the same histopathology.

PURPOSE: The etiology of the ascending testis is controversial. We propose that ascending testis, defined as a testis previously thought to be descended and later noted to be out of the scrotum, is due to mild hypogonadotropic hypogonadism affecting both testes. The diagnosis of these low types of true undescended testes is difficult to make clinically in children since they are frequently confused with retractile testes. In this study we compared testicular biopsies in a group of boys with ascending testes with those in boys who had an undescended testis since birth (primary undescended testis). MATERIALS AND METHODS: Between 1985 and 1995, 91 patients with ascending testes underwent orchiopexy and bilateral testis biopsy. The total germ cell count, processus vaginalis status, age at surgery and whether followup was done by a pediatrician or pediatric urologist were compared in patients with ascending and unilateral primary undescended testes. RESULTS: The total germ cell count was similar in the undescended and the contralateral descended testis in patients with ascending and primary undescended testes. The processus vaginalis was more likely to be closed in ascending testes (57% versus 36%, p = 0.0001). Age at surgery and the total germ cell count were similar in patients followed by pediatricians and pediatric urologists. CONCLUSIONS: The ascending testis has the same germ cell count as the primary undescended testis. Yearly followup by the primary care physician is recommended for patients with retractile testes.