Middle Ear Tophi: A Case Series of Two Unusual Lesions and a Report of Facial Weakness and Review of the Literature.

OBJECTIVE: Tophaceous lesions of the middle ear from calcium pyrophosphate deposition disease (CPPD, or pseudogout) and gout are infrequently reported. Recognizing its characteristic findings will allow clinicians to accurately narrow the differential diagnosis of bony-appearing middle ear lesions and improve management. PATIENTS: Two consecutive cases of tophaceous middle ear lesions presenting to a tertiary care center between January 2021 and December 2021. Neither with previous rheumatologic history. INTERVENTIONS: Surgical excision of tophaceous middle ear lesions. MAIN OUTCOME MEASURE: Improvements in facial weakness and conductive hearing loss. RESULTS: The first case was a 66-year-old gentleman with progressive conductive loss, ipsilateral progressive facial weakness over years, and an opaque, irregular-appearing tympanic membrane anterior to the malleus found to have CPPD on surgical pathology, with immediate postoperative improvement of facial function. The second was a 75-year-old gentleman with progressive conductive loss and similar appearing tympanic membrane as case 1, previously diagnosed with tympanosclerosis, found to have gout on surgical pathology. In both cases, the CT showed a heterogenous, bony-appearing lesion in the middle ear, and both tophaceous lesions were a of gritty, chalky consistency intraoperatively. CONCLUSION: Tophaceous lesions of the middle ear are rare but have similar findings. Notably, the tympanic membrane can appear opaque and irregular, and the CT demonstrates a radiopaque, heterogeneous appearance. Facial weakness is an unusual finding. Specimens of suspected tophi must be sent to pathology without formalin for accurate diagnosis.

Indolent T-lymphoblastic proliferation involving hepatocellular carcinoma-presentation in novel settings and comprehensive review of literature.

Indolent T-lymphoblastic proliferation (iT-LBP) is a rare, non-clonal, extrathymic lymphoid proliferation with an immature T cell phenotype, indolent clinical course, and excellent prognosis. Although their pathogenesis is unclear, they are reported to be associated with Castleman disease, follicular dendritic cell tumors/sarcomas, angioimmunoblastic T cell lymphoma, hepatocellular carcinoma (HCC), myasthenia gravis, and acinic cell carcinoma. There are around 51 reported cases of iT-LBP in the literature. Recognition and accurate diagnosis of this entity is critical as it shares morphologic and immunophenotypic features with an aggressive malignancy-acute T cell leukemia/lymphoma (T-ALL). IT-LBP in HCC post-liver transplant and in metastatic sites has not been reported in the literature. Two case reports of patients presenting with recurrent and metastatic HCC in post-liver transplant settings are described. A 50-year-old man with an end-stage liver disease with HCC underwent liver transplant. A year later, he developed pulmonary metastasis with associated iT-LBP. A 69-year-old man underwent liver transplant for end-stage liver disease and HCC. Eighteen months later, he developed recurrent HCC in the transplanted liver and omental metastasis; both sites showed HCC with iT-LBP. iT-LBP in both patients expressed TdT, CD3, and CD4 and lacked CD34 and clonal T cell receptor gene rearrangements. On retrospective review, the pre-transplant HCC specimens lacked iT-LBP. We present two cases of iT-LBP associated with HCC in novel settings-in post-liver transplant patients and in recurrent/metastatic sites of HCC. In addition, a comprehensive literature review of clinical, histological, and immunophenotypic characteristics of reported cases of iT-LBP is presented.

TRPV6 as a Putative Genomic Susceptibility Locus Influencing Racial Disparities in Cancer.

It is well established that African Americans exhibit higher incidence, higher mortality, and more aggressive forms of some cancers, including those of breast, prostate, colon, stomach, and cervix. Here we examine the ancestral haplotype of the TRPV6 calcium channel as a putative genomic factor in this racial divide. The minor (ancestral) allele frequency is 60% in people of African ancestry, but between 1% and 11% in all other populations. Research on TRPV6 structure/function, its association with specific cancers, and the evolutionary-ecological conditions that impacted selection of its haplotypes are synthesized to provide evidence for TRPV6 as a germline susceptibility locus in cancer. Recently elucidated mechanisms of TRPV6 channel deactivation are discussed in relation to the location of the allele favored in selection, suggesting a reduced capacity to inactivate the channel in those who have the ancestral haplotype. This could result in an excessively high cellular Ca2+, which has been implicated in cancer, for those in settings where calcium intake is far higher than in their ancestral environment. A recent report associating increasing calcium intake with a pattern of increase in aggressive prostate cancer in African-American but not European-American men may be related. If TRPV6 is found to be associated with cancer, further research would be warranted to improve risk assessment and examine interventions with the aim of improving cancer outcomes for people of African ancestry.