Canine melanocytic neoplasms have a highly variable biological behavior ranging from benign cutaneous melanocytomas to malignant oral melanomas that readily metastasize to lymph nodes and internal organs. This review focuses on the diagnosis and prognosis of canine melanocytic neoplasms. While pigmented melanocytic neoplasms can be diagnosed with fine-needle aspirates, an accurate prognosis requires surgical biopsy. However, differentiating amelanotic spindloid melanomas from soft tissue sarcomas is challenging and often requires immunohistochemical labeling with a diagnostic cocktail that contains antibodies against Melan-A, PNL-2, TRP-1, and TRP-2 as the current gold standard. For questionable cases, RNA expression analysis for TYR, CD34, and CALD can further differentiate these two entities. The diagnosis of amelanotic melanomas will be aided by submitting overlying and/or lateral flanking epithelium to identify junctional activity. Wide excision of lateral flanking epithelium is essential, as lentiginous spread is common for malignant mucosal melanomas. Combining histologic features (nuclear atypia, mitotic count, degree of pigmentation, level of infiltration, vascular invasion; tumor thickness and ulceration) with the Ki67 index provides the most detailed prognostic assessment. Sentinel lymph nodes should be evaluated in cases of suspected malignant melanomas using serial sectioning of the node combined with immunohistochemical labeling for Melan-A and PNL-2.

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A 10-year-old 38 kg (84 lbs) castrated male Labrador retriever mix was presented for fractionated radiation therapy (3 Gy per 18 fractions) following the narrow excision of a recurrent grade 3

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a clinical entity of aging humans that is characterized by cancer-associated mutations in white blood cells, without evidence of overt neoplasia. CHIP has been associated with an increased risk of hematologic cancers, cardiovascular disease, and all-cause mortality. We hypothesized that somatic mutations in specific genes associated with human CHIP would be detectable in the blood of aged dogs not known to have hematologic disorders. Methods: DNA from paired germline and whole blood samples from 93 geriatric canine patients affected by solid cancer were subjected to targeted next generation sequencing. Impact of the variants was predicted using Polymorphism Phenotyping version 2 software (PolyPhen-2, Harvard). Clinical and demographic data were extracted from medical records. Results: Somatic variants were detected in peripheral blood of four (4.3%) female dogs aged 12-15 years. Affected genes were ASXL1, KIT, SF3B1, TET2, RUNX1, and PPM1D. The variant in PPM1D was a nonsense mutation, while the other five variants were single nucleotide non-synonymous variants in protein coding regions of the genes. Following analysis by PolyPhen-2, the single nucleotide variants in KIT and SF3B1 were predicted to be benign, while the variants in ASXL1, TET2, and RUNX1 were predicted to be damaging. Conclusion: These results support the presence of variants in CHIP-associated genes in geriatric canids at a frequency similar to that observed in people, and the dog represents the first species in which the genetic lesion of CHIP has been documented. Further investigations are needed to confirm the association of this genetic lesion with clinical outcomes. Citation Format: Kimberley N. Sebastian, Hatice Gülçin Özer, Cory Howard, Laura Chadsey, Arletta Lozanski, Tzyy-Jye Doong, Gerard Lozanski, Wenjuan Ma, William C. Kisseberth, John C. Byrd, Bonnie K. Harrington. Clonal hematopoiesis of indeterminate potential in the companion dog [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1620.

Hepatic lymphoma is poorly characterized in cats and differentiating between inflammation and lymphomas is often difficult. The diagnosis of hepatic lymphoma in humans relies on recognition of specific patterns of lymphocytic infiltrates and clonality testing of antigen receptors. Herein, we defined similar patterns of lymphocytic infiltrates in hepatic biopsies of cats and correlated them with clonality to determine which patterns are predictive of lymphoma. A retrospective study was performed on surgical biopsies from 44 cats. The immunophenotype was characterized using CD3 and CD20 on all 44 samples. All 44 samples were tested using PCR for T-cell receptor gamma-gene rearrangements. PCR for immunoglobulin heavy chain gene rearrangements was performed on 24 of these cats. Four patterns of lymphocytic infiltrates were characterized: (1) tightly periportal, (2) periportal and centrilobular, (3) nodular, and (4) periportal with sinusoidal extension. Other histomorphologic features (fibrosis, biliary hyperplasia, bile ductopenia, bile duct targeting, hepatic hematopoiesis, lipogranulomas, lymphonodular aggregates, other inflammatory cells) were also evaluated. The sensitivity and specificity of the lymphocytic patterns to diagnose lymphomas were determined using Bayesian Hui–Walter analysis (BLCM) against clonality results. Lymphocytic patterns 2, 3, and 4 accurately diagnosed hepatic lymphomas with a sensitivity and specificity of 82% (CI 95%: 0.65, 0.96) and 77% (CI 95%: 0.54, 1.00), respectively. None of the other microscopic features evaluated were predictive of a lymphoma or inflammation. Our study identified specific patterns of lymphocytic infiltration that differentiate feline hepatic lymphoma from inflammation while other histologic features were not associated with an accurate diagnosis.