Limited Adenocarcinoma of the Prostate on Needle Core Biopsy

Context.— Grading small foci of prostate cancer on a needle biopsy is often difficult, yet the clinical significance of accurate grading remains uncertain. Objective.— To assess if grading of limited adenocarcinoma on prostate biopsy specimen is critical. Design.— We studied 295 consecutive patients undergoing extended-sextant biopsy with only 1-core involvement of adenocarcinoma, followed by radical prostatectomy. Results.— The linear tumor lengths on these biopsy specimens were: less than 1 mm (n = 114); 1 mm or more or less than 2 mm (n = 82); 2 mm or more or less than 3 mm (n = 35); and 3 mm or more (n = 64). Longer length was strongly associated with higher Grade Group (GG) on biopsy or prostatectomy specimen, higher risk of extraprostatic extension/seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen GG, higher grade was strongly associated with higher prostatectomy specimen GG, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens, compared with respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. Meanwhile, there were no significant differences in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length (eg, <1 mm [44.7%] versus ≥1/<2 mm [41.5%] versus ≥2/<3 mm [45.7%] versus ≥3 mm [46.9%]). Conclusions.— These results indicate that pathologists still need to make maximum efforts to grade relatively small prostate cancer on biopsy specimens.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy

Context.— Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. Objective.— To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. Design.— We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. Results.— PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1–3), pT (GG1–2/GG1–3/GG2/GG3), surgical margin status (GG1–3/GG3/GG5), or tumor volume (GG1–2/GG1–3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1–2 versus 3–6/1–3 versus 4–6/1–4 versus 5–6), RP GG (1–3 versus 4–6/1–4 versus 5–6), pT (1–2 versus 3–6/1–3 versus 4–6), pN (1–3 versus 4–6), or tumor volume (1–2 versus 3–6/1–4 versus 5–6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1–2/GG1–3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Conclusions.— Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1–3 cancer.

Rosai-Dorfman Disease of Bone and Soft Tissue

Context.— Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown pathogenesis that may be diagnostically difficult in extranodal sites. It is commonly an unsuspected diagnosis when arising in bone and soft tissue, especially when it presents without associated lymphadenopathy. Its variable clinical presentation and nonspecific imaging findings make the diagnosis quite challenging, particularly in small biopsies. The problem is compounded by its less-characteristic histomorphologic features in comparison with nodal disease. Awareness of the potential diagnostic pitfalls in Rosai-Dorfman disease of bone and soft tissue should raise the degree of diagnostic accuracy. Objective.— To review the clinical manifestations, imaging characteristics, and histomorphologic features of Rosai-Dorfman disease of bone and soft tissue along with a brief discussion of its differential diagnosis, pathogenesis, and current management. Data Sources.— Thorough review of the literature with focus on clinical manifestations, imaging findings, key histomorphologic features, pathogenesis, and treatment. Conclusions.— The diagnosis of Rosai-Dorfman disease of bone and soft tissue may be quite challenging because of its variable clinical presentation and nonspecific imaging findings. It may be asymptomatic without systemic manifestations or associated lymphadenopathy. The definitive diagnosis relies on histopathologic identification of the characteristic S-100–positive histiocytes demonstrating emperipolesis. Bone and soft tissue lesions tend to have lower numbers of characteristic histiocytes and less conspicuous emperipolesis and often demonstrate areas of fibrosis or storiform spindle cell areas resembling fibrohistiocytic lesions. Awareness of these unusual features is necessary in order to consider Rosai-Dorfman disease in the differential diagnosis when confronting these rare and often misleading lesions.

Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma

Context.— Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). Objective.— To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. Design.— Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, gender, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). Results.— PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, gender, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the two groups. CD4 count of more than 200/μL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. Conclusions.— PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

Clinicopathologic Appearance of Advanced Ketoacidosis With Basal Vacuolation in Renal Tubules

Context.— Basal vacuolization (BV) in renal tubules is a histopathologic hallmark of advanced ketoacidosis that enables us to retrospectively diagnose these cases. Objective.— To clarify the pathologic background and serologic findings of ketoacidosis with BV, and to reveal the pathologic findings by each pathologic background. Design.— We examined 664 serial autopsy cases. A systemic histopathologic examination and measurement of serum β-hydroxybutyrate concentration were performed for the cases with BV. The extent of steatosis and fibrosis in the organs and the degree of coronary artery stenosis were semiquantitatively investigated. Immunohistochemistry for adipophilin was also performed to analyze its usefulness for the pathologic diagnosis. Results.— Basal vacuolization was found in 16 cases, all of which showed a pathologic serum β-hydroxybutyrate concentration. The main background of ketoacidosis was considered as alcohol abuse in 6 cases, diabetes in 5, malnutrition in 3, and hypothermia and infection in 1 case each. Severe hepatic fibrosis was observed only in the alcohol-abuser group. Moreover, cardiac steatosis was more severe in patients with possible alcohol abuse than in those with other causes. Immunohistochemistry for adipophilin showed immunoreactivity consistent with BV in 13 of 16 cases. There was no correlation between β-hydroxybutyrate concentration and either the postmortem or storage interval. Conclusions.— Basal vacuolization may be a useful finding for detecting ketoacidosis cases in a postmortem investigation. Serum β-hydroxybutyrate was a stable and reliable compound for the definitive diagnosis of ketoacidosis in such cases. The present study showed that pathologic changes in some organs may vary by each pathologic background of ketoacidosis with BV.

BCR-ABL1 (p210) Transcript Kinetics

Context.— Delta checks are a powerful technique for monitoring clinical assays in many disciplines but have not been routinely used in molecular testing. Objective.— To determine if the biologically determined kinetics of BCR-ABL1's rise and fall could allow the development of a delta check in BCR-ABL1 testing. Design.— Nine years of BCR-ABL1 p210 results were evaluated and patients with 3 or more results were selected for inclusion. The kinetics of these percentages of international standard values were plotted against time along with the median and the 90th and 95th percentile lines. A Monte Carlo simulation of a batch mix-up was performed for 6 months of data to determine the efficacy of the proposed cutoff. Results.— The median kinetics showed a 1-log drop of the percentage of international standard in 90 days, with less than 5% of cases showing faster than a 2-log drop in 90 days, and less than 2.5% showing a faster than 3-log drop in 90 days (extrapolated to 1 log in 30 days). The Monte Carlo simulation of a batch mix-up showed that an average batch mix-up of 23 samples could routinely be flagged by this cutoff, albeit with wide variance. Conclusions.— These results suggest that using a drop in the percentage of international standard of greater than 1 log in 30 days can be a useful trigger in implementing a delta-check system for this molecular test.

Nonlymphoid Hematopoietic Diseases Presenting in Bone, Soft Tissue, and Other Extranodal Sites

Context.— Although rare in everyday practice, the initial presentation of hematopoietic neoplasms other than lymphoma in the musculoskeletal system and other extranodal sites can generate challenging diagnostic problems for surgical pathologists. Objective.— To review the morphologic and immunophenotypic features of various nonlymphoid hematopoietic diseases presenting at extranodal sites, with emphasis on the inherent diagnostic pitfalls and differential diagnoses of these entities to aid surgical pathologists in their accurate recognition. Data Sources.— Cases reviewed herein represent both in-house and consult cases seen at our institution between 2010 and 2021. Conclusions.— Entities that present in this way include myeloid neoplasms and histiocytic/dendritic cell neoplasms. These tumors commonly cause nonspecific symptoms, and their histologic appearance can overlap with a variety of benign neoplasms and reactive processes. This can lead to delay in diagnosis and intervention with potentially lifesaving therapy; thus, accurate and expedient recognition is of paramount importance.