Faculty Bibliography

Malignancy associated with ileal neobladders or ileal conduits in postradical cystectomy patients is rare. Yet, recurrent urothelial carcinoma or new primary cancers, such as adenocarcinoma, enteric type (EA), are potential complications that pose significant clinical challenges. This study aimed to evaluate the incidence, clinical outcomes, and management strategies for malignancies in patients with ileal neobladders or ileal conduits. A retrospective review was conducted at 3 large academic institutions, identifying 10 cases of malignant tumors arising in ileal neobladders or ileal conduits over a period of 10 years. The study cohort included 9 male and 1 female patient aged 56 to 92 years (mean age = 68.2 y). Data on clinical presentation, management, pathology, and outcomes were collected, with a focus on recurrence and disease-specific survival rates. Seven of 10 patients (all males) were initially diagnosed with invasive high-grade urothelial carcinoma (IHGUC), whereas 3 patients had a history of bladder augmentation with colonic tissue (BA) for benign etiologies. Of patients with IHGUC, 2 patients received neoadjuvant chemotherapy, 1 received a combination of chemotherapy agents, and 3 patients underwent intravesical BCG therapy. All IHGUC exhibited conventional morphology without divergent differentiation. Pathologic staging of the cystectomy for IHGUC ranged from pTa to pT3a, with 4 cases showing lymph node metastasis. IHGUC recurrence was detected in 6 of 7 patients with a latency period range of 7 months to 6.7 years (mean 37 mo) and all tumors again exhibiting conventional morphology without divergent differentiation. IHGUC recurrence demonstrated a pathologic stage ranging from pT2 to pT4, and 5 died (mean = 4.2 mo), whereas 1 patient remains alive and on surveillance. EA occurred in 4 patients, including 3 BA patients and 2 foci in 1 patient with a neobladder for IHGUC. Staging of patients with EA ranged from pTis to pT2 developing 31 to 55 years postsurgery. Three of 5 EA cases were associated with a precursor lesion including 2 tubular adenoma with high-grade dysplasia, and 1 sessile serrated lesion with dysplasia. EA patients had relatively favorable outcomes compared with IHGUC patients,  with all surviving patients currently on surveillance though with one case demonstrating nodal metastasis. Although rare, malignancies in ileal neobladders or ileal conduits are a serious complication. Although IHGUC recurrence often leads to poor survival, EA patients-especially those with prior bladder augmentation-seem to be associated with better survival outcomes. The long latency period for IHGUC recurrence and the favorable prognosis for EA underscore the need for vigilant long-term surveillance.

PURPOSE/OBJECTIVE:Both MRI and PSMA PET/CT are often utilized for staging of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). Recent studies found that PSMA PET/CT was superior to MRI in correctly identifying final pathological tumor stage, dominant nodule, extraprostatic extension (EPE), and small areas of clinically significant PCa. We sought to determine if PSMA PET/CT was superior to MRI in both locoregional staging of PCa and potential focal therapy planning. METHODS:We retrospectively analyzed our prospectively collected, IRB-approved database of all patients who underwent prostatectomy at one institution between 10/1/2019-2/29/2024. Patients were excluded if they did not pre-operatively undergo both MRI and PSMA PET/CT. 2 × 2 tables were used to compare each modality to the "gold standard" of prostatectomy specimen in both the proper detection of laterality and presence of EPE. Sensitivities and specificities were compared using a chi-squared test. HR v. IR groups were compared using a Wilcoxon rank sum test for continuous variables and Fisher's exact test for categorical variables. Results were considered significant at p < 0.05. RESULTS:580 patients underwent prostatectomy within the specified timeframe. 78 patients met inclusion criteria. MRI was more sensitive in the detection of EPE than PSMA PET/CT (23.5% v. 7.8%, p = 0.0294). MRI and PSMA PET/CT were similar in the specificity of EPE detection. In the identification of laterality, MRI was more specific (86.7% v. 56.7%, p = 0.0099), while sensitivities were similar between the modalities. CONCLUSIONS:MRI was superior to PSMA PET/CT in the proper detection of both EPE and laterality in patients with IR and HR PCa.

BACKGROUND:Squamous cells are uncommon in thyroid fine needle aspirations (FNAs) presenting diagnostic challenges. We report our multi-institutional experience. MATERIALS AND METHOD/METHODS:The electronic data were searched for thyroid FNAs containing squamous cells at the Johns Hopkins Medicine, New York University Langone Hospital, United States, and Fimlab Laboratories, Finland (2001-2023). The patients' demographics, clinical history, and pathologic diagnosis were recorded. RESULTS:One hundred and seven cases (103 patients) were identified 35 males and 68 females (median age 58 years). Forty-eight cases (44.9%) were malignant, primary carcinomas with squamous features, such as anaplastic thyroid carcinoma (ATC), and metastatic or directly invasive squamous cell carcinomas (SqCC) including oral, oropharyngeal (HPV-related), esophageal, and laryngeal SqCC. Twenty-seven cases (25.2%) contained benign squamous cells with cystic background, suggestive of developmental cysts. Nineteen cases (17.8%) contained metaplastic benign squamous cells within an adenomatoid nodule. Seven cases (6.5%) contained atypical squamous cells. Four cases (3.7%) showed squamous cells with bacterial or fungal organisms, suggestive of esophageal fistula/diverticulum, and two cases (1.9%) contained benign squamous cells with unknown source. Thirty-six cases had surgical follow-up, 33 (91.7%) were concordant (23 metastatic or directly invasive SqCC, 8 undifferentiated/ATC, and 10 papillary thyroid carcinoma). Ancillary studies were used confirming HPV-related SqCC, or therapeutic targets (BRAF V600E), with highly variable staining in ATC. CONCLUSION/CONCLUSIONS:Squamous cells in thyroid FNAs carry a broad differential diagnosis with variable prognoses. It is crucial to interpret squamous cells in the context of clinical and radiographic findings for optimal patient care.

When multiple cores are biopsied from a single magnetic resonance imaging (MRI)-targeted lesion, Gleason grade may be assigned for each core separately or for all cores of the lesion in aggregate. Because of the potential for disparate grades, an optimal method for pathology reporting MRI lesion grade awaits validation. We examined our institutional experience on the concordance of biopsy grade with subsequent radical prostatectomy (RP) grade of targeted lesions when grade is determined on individual versus aggregate core basis. For 317 patients (with 367 lesions) who underwent MRI-targeted biopsy followed by RP, targeted lesion grade was assigned as (1) global Grade Group (GG), aggregated positive cores; (2) highest GG (highest grade in single biopsy core); and (3) largest volume GG (grade in the core with longest cancer linear length). The 3 biopsy grades were compared (equivalence, upgrade, or downgrade) with the final grade of the lesion in the RP, using κ and weighted κ coefficients. The biopsy global, highest, and largest GGs were the same as the final RP GG in 73%, 68%, 62% cases, respectively (weighted κ: 0.77, 0.79, and 0.71). For cases where the targeted lesion biopsy grade scores differed from each other when assigned by global, highest, and largest GG, the concordance with the targeted lesion RP GG was 69%, 52%, 31% for biopsy global, highest, and largest GGs tumors (weighted κ: 0.65, 0.68, 0.59). Overall, global, highest, and largest GG of the targeted biopsy show substantial agreement with RP-targeted lesion GG, however targeted global GG yields slightly better agreement than either targeted highest or largest GG. This becomes more apparent in nearly one third of cases when each of the 3 targeted lesion level biopsy scores differ. These results support the use of global (aggregate) GG for reporting of MRI lesion-targeted biopsies, while further validations are awaited.

Squamous cell carcinoma of the anal canal remains rare, with metastatic disease even less commonly reported. We present a case of a patient with both a prior history of squamous cell carcinoma of the anal canal as well as breast cancer, who was without evidence of disease for 1 year. She was subsequently found to have FDG-avid mediastinal lymphadenopathy, initially assumed to be related to her more recent breast cancer. However, a biopsy confirmed recurrent anal cancer, with HPV infection. This represents a novel site of spread for anal cancer, one not yet reported in the literature.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the genes encoding polycystin 1 and polycystin 2 (PKD1 and PKD2, respectively), leading to florid cystic change of the renal parenchyma. The incidence of carcinoma associated with ADPKD remains unclear although there are studies to suggest that the incidence may be higher.
Design(s): We queried our department pathology database for surgical specimens with ADPKD from 1990 to 2020. We evaluated these cases for the presence of associated malignant or benign neoplasia, as well as pathological and clinical parameters.
Result(s): The majority of the surgical specimens are kidney explants with a clinical diagnosis of ADPKD and the status of end stage kidney diseases. All specimens showed radiological, gross and microscopic features of ADPKD. Eight of 33 ADPKD patients with kidney resection specimens examined contained a malignant neoplasm, including 2 patients with bilateral malignancy. The types of renal cell carcinoma (RCC) associated with the following types: four cases of clear cell RCC, two cases of papillary RCC, type 2, two cases of unclassified high grade RCC, one case of unclassified low grade, as well as one case of TFE3 translocated RCC. Associated carcinomas ranged in size from less than 1 cm to 12 cm. One case with a concurrent oncocytoma and several cases with associated papillary adenoma were also reported.
Conclusion(s): In this cohort, a wide distribution of renal cell carcinoma subtypes were observed, with clear cell RCC being the most common type. The incidence of associated malignancy (24%) is higher than previously reported by Jilg et al. 2013 (5%), possibly due to differences in patient management or patient populations between the institutions. This case series highlights the high occurrence of carcinoma in APKD nephrectomies suggesting a clinical risk of malignancy in patients with ADPKD. Additionally this case series reports the first case of a TFE3 translocated renal cell carcinoma arising synchronously with a contralateral clear cell renal cell carcinoma in a patient with ADPKD. The heterogeneity of renal carcinoma subtypes within the group (and within contralateral kidneys in one patient with bilateral involvement) suggests that stimuli for tumorigenesis arise at the kidney microenvironment level rather than on the basis of gene mutation alone. Accrual of an expanded cohort of patients is planned to enable confirmation of differences between carcinomas arising in the setting of ADPKD versus those arising in end stage renal disease due to other causes, and in the sporadic setting. Furthermore a role for molecular studies is suggested to evaluate if any of the ADPKD causing mutations (PKD1, PKD2, or other) is associated with the development of carcinoma

The differential diagnosis of renal cell neoplasms with solid or nested architecture and eosinophilic cytoplasm has become increasingly complex. Despite recent advances in classifying a number of entities exhibiting this morphology, some tumors remain in the unclassified category. Here we describe a morphologically distinct group of sporadic renal cell carcinoma (RCC) with predominantly nested architecture, eosinophilic, and remarkably vacuolated cytoplasm retrospectively identified from a cohort of previously unclassified tumors. We examined the clinicopathologic and immunohistochemical features of these tumors and investigated their mutational and copy number alterations using a targeted next-generation sequencing platform. The study included 7 patients with a mean age of 54 years (range: 40 to 68 y) and a male to female ratio of 3:4. All patients presented with a solitary renal mass and had no prior medical or family history raising concern for syndromic conditions. Tumors were well-circumscribed, unencapsulated, and comprised of nests of eosinophilic cells in a hypocellular and often edematous stroma. Tumor cells had round nuclei with prominent nucleoli and granular cytoplasm with striking vacuolization. Thick-walled vessels and calcifications were also frequently present, whereas increased mitotic activity, necrosis, foamy histiocytes or lymphocytic infiltrates were not identified. All cases were positive for PAX8, had retained expression of SDHB and FH, and exhibited a CK7-/CK20- phenotype. While cathepsin-K was positive in 5 cases, none exhibited immunoreactivity to HMB45 or Melan A, or TFE3 immunostaining. Next-generation sequencing identified somatic inactivating mutations of TSC2 (3/5 tumors tested) or activating mutations of MTOR (2/5) as the primary molecular alterations, consistent with hyperactive mTOR complex 1 signaling which was further demonstrated by phospho-S6 and phospho-4E-BP1 immunostaining. Copy number analysis revealed a loss of chromosome 1 in both cases with MTOR mutation. These tumors represent a novel subset of sporadic RCC characterized by alterations in TSC1-TSC2 complex or the mTOR complex 1 pathway. Recognition of their characteristic morphologic and immunophenotypic features will allow them to be readily identified and separated from the unclassified RCC category.