Total submission of standard- and extended-template pelvic LN dissections for prostate cancer
There are no consensus guidelines for submitting pelvic lymph node dissection specimens for radical prostatectomies. A minority of laboratories submit the specimens in their entirety, including the authors’ institution, which does so for standard- and extended-template pelvic lymph node dissections (PLND). To investigate the utility of submitting entire PLND specimens for prostate cancer and how it impacts patients and the laboratory, the authors performed a retrospective study of 733 cases of radical prostatectomies with PLND. Reports and slides with positive lymph nodes (LNs) were reviewed. Data on LN yield, cassette usage, and the impact of submitting the remaining fat after dissection of grossly identifiable LNs were assessed. Most cases involved submitting extra cassettes for remaining fat (97.5 percent, n = 697 of 715). Extended PLND yielded a higher mean number of total and positive LNs than standard PLND (P < .001). However, extended PLND required significantly more cassettes to accomodate the remaining fat (mean, eight; range, 0–44). Poor correlation was noted between the number of cassettes submitted for PLND and total LN and positive LN yield, as well as between the number of cassettes submitted for the remaining fat and additional LN yield. Most positive LNs were grossly identified (88.5 percent, n = 139 of 157) and were typically larger than those that were not grossly identified. Only four cases (0.6 percent, n = four of 697) would have been understaged without submission of a complete PLND. The authors concluded that submitting PLNDs in their entirety increases detection of metastasis and LN yield but also significantly increases workload, with only minimal impact on patient management. Therefore, the authors recommend following meticulous grossing techniques to identify all LNs in standard- and extended-template PLND specimens for prostate cancer. The remaining fat of PLND specimens need not be submitted after meticulous dissection of LNs.
Gafeer MM, Arriola AGP. The hunt for lymph nodes: Is total submission of standard-template and extended-template pelvic lymph node dissections necessary for detecting metastatic prostate cancer? Arch Pathol Lab Med. 2023;147(12):1466–1470.
Correspondence: Dr. Aileen Grace P. Arriola at aileengrace.arriola@tuhs.temple.edu
Impact of decalcification, cold ischemia, and deglycosylation on PD-L1 antibodies with different binding epitopes
Programmed cell death ligand 1 expression levels in tumors have demonstrated clinical utility across many cancer types and are used to determine eligibility for cancer treatment. Several independently developed PD-L1 IHC predictive assays are commercially available and have demonstrated varying levels of staining. This has generated interest in understanding the similarities and differences between the assays. The authors previously identified epitopes in the internal and external domains of PD-L1 bound by antibodies in routine clinical use (SP263, SP142, 22C3, and 28-8). Variance in the performance of assays using these antibodies, observed following exposure to such preanalytical factors as decalcification, cold ischemia, and duration of fixation, encouraged additional investigation of antibody-binding sites to understand whether binding site structures or conformations contribute to differential PD-L1 IHC assay staining. The authors further investigated the epitopes on PD-L1 bound by these antibodies alongside the major clones used in laboratory-developed tests (E1L3N, QR1, and 73-10). Characterization of QR1 and 73-10 clones demonstrated that both bind the PD-L1 C-terminal internal domain, similar to SP263/SP142. The authors also showed that under suboptimal decalcification or fixation conditions, the performance of internal domain antibodies is less detrimentally affected than that of the external domain antibodies 22C3/28-8. In addition, they indicated that the binding sites of external domain antibodies are susceptible to deglycosylation and conformational structural changes, which directly result in IHC staining reduction or loss. The binding sites of internal domain antibodies were unaffected by deglycosylation or conformational structural change. This study demonstrates that the location and conformation of binding sites, recognized by antibodies employed in PD-L1 diagnostic assays, differ significantly and exhibit differing degrees of robustness. These findings should reinforce the need for vigilance when performing clinical testing with various PD-L1 IHC assays.
Lawson NL, Scorer PW, Williams GH, et al. Impact of decalcification, cold ischemia, and deglycosylation on performance of programmed cell death ligand-1 antibodies with different binding epitopes: comparison of 7 clones. Mod Pathol. 2023;36. doi:10.1016/j.modpat.2023.100220
Correspondence: Dr. Nicola Lawson at nicola.lawson@astrazeneca.com
Pathology reports for spontaneous preterm birth from general surgical pathologists vs. perinatal pathologist
Placental examination, frequently performed by general surgical pathologists, plays an important role in understanding patient outcomes and explaining the underlying mechanisms leading to preterm birth. The authors conducted a secondary analysis of a large retrospective study of the placental pathology in recurrent preterm birth to compare diagnoses between general surgical pathologists (GSPs) and a perinatal pathologist (PP). For the parent study, preterm placentas were examined between 2009 and 2018 at a single institution. Pathology diagnoses were coded into four categories—acute inflammation, chronic inflammation, fetal vascular malperfusion, and maternal vascular malperfusion—based on original reports of the GSPs and second review by the PP. The study included 331 placentas initially examined by 17 GSPs. The prevalence of all four placental diagnostic categories was higher for the PP, and 49.2 percent of placentas finalized by GSPs had no diagnostic findings. Agreement between GSPs and the PP was highest for acute inflammation (κ = 0.50; weak agreement). There was no agreement for maternal vascular malperfusion (κ = 0.063), chronic inflammation (κ = 0.0026), and fetal vascular malperfusion (κ = –0.018). Chronic basal deciduitis with plasma cells had the highest false-negative rate (missed by GSPs in 107 cases). Villous infarction had the highest false-positive rate (overcalled in 28 of 41 [68 percent] cases), with the majority of the “infarcts” representing intervillous thrombi. The authors found very poor interobserver agreement between GSPs and the PP when assessing placental pathology. Acute inflammation had the highest level of agreement between the two pathologist types, but it was only weak to moderate. The authors concluded that these findings are a call to action to implement educational efforts and structural or organizational changes that make placental pathology reporting more consistent.
Ernst LM, Basic E, Freedman AA, et al. Comparison of placental pathology reports from spontaneous preterm births finalized by general surgical pathologists versus perinatal pathologist: A call to action. Am J Surg Pathol. 2023;47(10):1116–1121.
Correspondence: Dr. Linda M. Ernst at lernst@northshore.org