Blood testis barrier revisited—Analysis of post‐chemotherapy germ cell tumor orchidectomy and retroperitoneal lymph node dissection specimens

Abstract

Objective To assess the response of chemotherapy on the primary tumor, compare it with the response in retroperitoneal disease, and study factors associated with pathological complete response. Methods We conducted a retrospective audit of all high inguinal orchidectomies (HIOs) performed after chemotherapy between 2012 and 2019 at a tertiary cancer center in India. Patient characteristics and histopathological response were extracted from electronic medical records, and predictors of testicular disease response were assessed. Results Of the 260 retroperitoneal lymph node dissections (RPLNDs) performed in the study period, 37 HIOs (14.23%) were carried out after chemotherapy. The median age of presentation was 28 years (16–41). Histopathology was divided into a viable tumor, mature teratoma, and necrosis/scarring. Residual disease was seen in 17 RPLND (46.0%) and 18 HIO (48.6%) specimens respectively. Of these 18, three patients had a residual viable tumor in the testis, and the remaining had a mature teratoma. Clinico‐radiological assessment showed an average reduction of 61% in testicular disease size following chemotherapy. On orchidectomy histopathological assessment, the median tumor size was 9, 4, and 1.5 cm in specimens with a viable tumor, mature teratoma, and necrosis/scarring, respectively. Conclusions A low threshold for upfront chemotherapy in patients with a high disease burden may be considered as tumors within the testis respond to chemotherapy in more than half of the patients. Discordance rates of residual cancer in RPLND and HIO specimens exist but post‐chemotherapy tumor size in testis correlates with the presence of a residual viable tumor.

The utility of cfDNA in TGCT patient management: a systematic review

“…The barrier is strong enough to even limit the effect of chemotherapy, with most childhood leukemia relapses being in the testis. 55 The average concentration of cfDNA in patients with TGCT was measured at 10 ng/mL while healthy controls had 1 ng/mL, which showed discriminatory power. 40 However, multiple studies have shown that the concentration of cfDNA in the blood of healthy controls is highly variable and ranges from 0 to 100 ng/mL with the average value of 30 ng/mL, while in patients with cancer the range is 5–1000 ng/mL.…”

“… 23 , 61 Everything from the time of day when sampling, the satiety and exertion level of the patient, the type of needle in blood drawing, the selection of blood tubes, sample transportation, the temperature, and time that takes from the blood to be processed, choice between blood serum and plasma, centrifugation protocols, storage of plasma or serum before cfDNA isolation, freeze-thawing of plasma or serum, HIL (hemolysis, icterus and lipemia) presence, choice of cfDNA isolation and quantification methods as well as cfDNA storage methods and duration has been shown to create variability in the final analysis results, especially with regards to cfDNA concentration and fragmentation. 23 , 62 – 66 This is both due to the effects of these variables on cfDNA degradation and isolation, but even more importantly, variations in sample processing can lead to genomic DNA contamination. 23 , 62 , 67 Even when certain procedures have become widely accepted or suggested, such as double-step centrifugation in blood plasma or serum preparation, minimizing the number of freeze-thawing events, usage of blood plasma and use of automated methods for cfDNA isolation the variations persist.…”