Improved Graft Function following Desensitization of Anti-AT1R and Autoantibodies in a Heart Transplant Recipient Negative for Donor-Specific Antibodies with Antibody-Mediated Rejection: A Case Report.

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs.

The Hunt for Lymph Nodes: Is Total Submission of Standard-Template and Extended-Template Pelvic Lymph Node Dissections Necessary for Detecting Metastatic Prostate Cancer?

CONTEXT.­: There are no consensus guidelines on submission of pelvic lymph node dissection (PLND) specimens for radical prostatectomies. Complete submission is only performed by a minority of laboratories. Our institution has been following this practice for standard-template and extended-template PLND. OBJECTIVE.­: To investigate the utility of total submission of PLND specimens for prostate cancer and understand its impact on patients and the laboratory. DESIGN.­: Retrospective study examining 733 cases of radical prostatectomies with PLND performed at our institution. Reports and slides with positive lymph nodes (LNs) were reviewed. Data on LN yield, cassette usage, and impact of submission of remaining fat after dissection of grossly identifiable LNs were assessed. RESULTS.­: Most cases involved submission of extra cassettes for remaining fat (97.5%, n = 697 of 715). Extended PLND yielded a higher mean number of total and positive LNs versus standard PLND (P < .001). However, extended PLND required significantly more cassettes for remaining fat (mean, 8; range, 0-44). There was poor correlation between number of cassettes submitted for PLND with total and positive LN yield and between remaining fat with LN yield. Most positive LNs were grossly identified (88.5%, n = 139 of 157) and were typically larger than those not. Only 4 cases (0.6%, n = 4 of 697) would have been understaged without complete submission of PLND. CONCLUSIONS.­: Total submission of PLND increases detection of metastasis and LN yield yet increases workload significantly with only minimal patient management impact. Hence, we recommend that meticulous gross identification and submission of all LNs be pursued without the need to submit the remaining fat of PLND.

Pilomatrixoma and its Imitators.

Introduction: Pilomatrixomas are benign neoplasms derived from hair follicle matrix cells. They are among the most common soft tissue head and neck tumors of childhood. Pilomatrixomas are typically isolated, slow-growing, firm, nontender masses that are adherent to the epidermis but mobile in the subcutaneous plane. This clinical presentation is so characteristic that many experienced surgeons will excise suspected pilomatrixomas without prior imaging. We reviewed the results of this approach to determine whether physical examination alone differentiates pilomatrixomas from other similar soft tissue lesions of the pediatric head and neck. Methods: Computerized review of all pilomatrixomas over a 20-year period in a single academic pediatric otolaryngology practice. Results: 18 patients presented to our pediatric otolaryngology practice between 2001 and 2021 with historical and physical findings consistent with pilomatrixoma. Of the 18 patients, 7 were male and 11 were female. Ages ranged from 1.5 to 14 years, with a mean of 7.5 years. Most of the lesions (12) were located in the head and face, while the rest (6) were found in the neck. All patients were treated with complete surgical excision. Pathology confirmed pilomatrixoma in 15 patients. The remaining 3 children were found to have an epidermal inclusion cyst, a ruptured trichilemmal cyst, and a giant molluscum contagiosum lesion, respectively. One additional patient presented with a small lesion of the auricular helix that was thought to be a dermoid cyst, but proved to be a pilomatrixoma on histologic examination. Discussion: As pilomatrixomas are common and have a very characteristic presentation, surgical excision without prior diagnostic imaging will lead to correct treatment in the majority of cases. High resolution ultrasonography can help to confirm the diagnosis preoperatively, but is not definitive in large case series. Most of the cystic lesions that imitate pilomatrixoma will ultimately require surgical excision.

PD-L1 Expression Reveals Significant Association With Squamous Differentiation in Upper Tract Urothelial Carcinoma.

OBJECTIVES: Limited literature is available on the tumor microenvironment (TM) of upper tract urothelial carcinoma (UTUC). This study comprehensively reviews programmed death 1 receptor (PD-1)-positive and CD8+ tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on tumor epithelium (TE). METHODS: Seventy-two nephroureterectomy specimens were analyzed for PD-L1, PD-1, and CD8. One percent or more tumor and lymphohistiocyte PD-L1 expression was considered positive. TIL density by H&E was scored semiquantitatively from 0 to 3, and CD8+ and PD-1+ TILs were quantified in hotspots. RESULTS: Of the cases, 37.5% demonstrated PD-L1+ on TE. PD-L1+ TE showed an association with pathologic stage (P = .01), squamous differentiation (SqD) (P < .001), TILs by H&E (P = .02), PD-1+ peritumoral TILs (P = .01), and PD-L1+ peritumoral lymphohistiocytes (P = .002). Finally, there was a significant difference in PD-1+ peritumoral TILs in cases with SqD vs no SqD (P = .03). CONCLUSIONS: Aggressive UTUC is associated with a distinct TM. Furthermore, TM of UTUC-SqD was distinctly different from those with no SqD, warranting study in a larger cohort.

The use of cytological material in melanoma for programmed death ligand 1 immunostaining.

OBJECTIVE: Interest in immune therapies has exploded since the 2014 approval of first-generation programmed cell death 1 blocking antibodies for use in advanced melanoma. Clinical trials have focused primarily on histological material as the gold standard for evaluating programmed death ligand 1 (PD-L1) by immunoperoxidase (IPOX) studies. Studies validating the use of cytological specimens in the assessment of PD-L1 by IPOX staining are needed to optimise tissue utilisation in complementary diagnostic testing. METHODS: Twenty-three melanoma surgical biopsies (SBx) with an IPOX stain for PD-L1 clone 28-8, and a corresponding cytological specimen from the same patient, adequate for PD-L1 evaluation, were selected. Cell-transfer cell blocks (CBs) and conventional CBs were used to perform PD-L1 testing. Tumour proportion scores (TPS) were generated and the results were correlated with the corresponding SBx. RESULTS: Overall agreement (OA) using a ≥1% TPS cut-off for SBx compared to CB was 88.9%, positive percent agreement (PPA) was 87.5%, and negative percent agreement (NPA) was 100%, OA using a ≥5% TPS cut-off was 55.6%, PPA was 42.9%, and NPA was 100%. SBx compared to cell-transfer CB using a ≥1% TPS cut-off had an OA of 65.2%, a PPA of 55.6%, and a NPA of 100%, while a ≥5% TPS cut-off generated an OA of 52.2%, a PPA of 35.7%, and a NPA of 77.8%. CONCLUSION: Our results demonstrate that cytological material, particularly conventional CB, is a viable alternative for evaluating PD-L1 in melanoma cases and suggest that a lower threshold (≥1%) may be beneficial when evaluating cytological material.

Malignant Mixed Epithelial and Stromal Tumor of the Kidney With 2 Simultaneous Renal Carcinomas in a Male Patient: Case Report and Review of the Literature.

The majority of mixed epithelial and stromal tumors (MEST) of the kidney are benign entities found in female patients. Malignant MEST of the kidney is an extremely rare entity that often behaves clinically similar to an undifferentiated sarcoma. We report a case of a malignant MEST with synchronous papillary and clear cell renal cell carcinomas (RCCs) in a 61-year-old Caucasian man who presented with an incidental finding of a left renal mass on workup for back pain. The patient underwent a left radical nephrectomy, with histopathology confirming a malignant MEST, intimately associated papillary RCC, and separate adjacent focus of clear cell RCC.

The usefulness of various cytologic specimen preparations for PD-L1 immunostaining in non-small cell lung carcinoma.

INTRODUCTION: Evaluation of programmed cell death ligand-1 (PD-L1) on formalin-fixed paraffin-embedded (FFPE) histologic specimens is required for immunotherapy with pembrolizumab in non-small cell lung carcinoma (NSCLC). A significant percent of patients may be diagnosed on cytology samples alone; however, FFPE tissue may not always be available. Here, we evaluated the feasibility of PD-L1 staining on a variety of cytologic preparations including conventional cell blocks (CB), cell-transfer cell blocks (CTCB), and direct smears. MATERIALS AND METHODS: We identified 30 NSCLC cytology cases that had PD-L1 status evaluated on a concurrent core needle biopsy. Papanicolaou-stained smears (PS) were reviewed and a moderately cellular smear was selected per case to prepare a CTCB. CTCB, CB, and PS (when available) were stained with PD-L1 22C3 and tumor proportion scores (TPS) were compared across all preparations with the concurrent core biopsies. RESULTS: Concordance of PD-L1 positivity in CB and PS versus core biopsy was high, 80% (12 of 15) and 94.4% (17 of 18), respectively. CTCB versus core biopsy concordance was lower in comparison, 62% (13 of 21) for PD-L1 positivity. Overall, TPS was lower in CTCB compared with CB and PS. Among the 3 preparations, CTCB and CB sections were easier to interpret as PS displayed various artifactual staining patterns. CONCLUSIONS: In summary, our study demonstrates that CB and PS preparations are suitable surrogates for histologic FFPE tissue for determining PD-L1 status in NSCLC patients. CTCBs, on the other hand, show high discordance and are not optimal specimens. Pre-analytic factors in unconventional cytology preparations may need optimization and negative results should be interpreted with caution.

Staged management of giant bilateral perinephric adipocytic neoplasms.

We present a patient with giant bilateral perinephric masses favored to represent liposarcoma preoperatively. Bilateral renal involvement posed a clinical challenge; careful histologic assessment and surgical planning allowed preservation of renal function.

Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature.

Retiform hemangioendothelioma (RH) is a rare vascular neoplasm with a high rate of local recurrence and low metastatic potential. We describe an unusual case of RH in a 45-year-old patient with Milroy disease, with a prominent solid component diffusely involving a chronic lymphedematous leg. This case is consistent with the postulated relationship between lymphedema and vascular neoplasms developing as a result of local immune dysfunction, and highlights the need to closely monitor patients with Milroy disease for pathologic changes. Our case highlights a unique example of RH with atypical features. There are several noteworthy unusual clinical and histologic findings including diffuse involvement of an entire limb, solid component with cytologic atypia, D2-40 expression, and first-time-reported association with Milroy disease. Given the atypical histologic presentation of cytologic atypia, solid areas and atypical immunohistochemical profile with D2-40 positivity, this case could cause diagnostic difficulty, especially in the setting of such a broad clinical differential.