Histiocytic Sarcoma With CCND1 Gene Rearrangement Clonally Related and Transdifferentiated From Mantle Cell Lymphoma.

OBJECTIVES: Histiocytic neoplasms demonstrate shared gene translocations and clonal immunoglobulin gene rearrangements in cases of associated B-cell lymphomas. However, the evolution of these related disease processes remains largely uncertain, especially in the setting of a prior mantle cell lymphoma. METHODS: We describe a unique case of a histiocytic sarcoma that transdifferentiated from blastoid mantle cell lymphoma after extensive therapy. Cytogenic and molecular studies were performed and provided evidence for clonal progression. RESULTS: We present the first reported case of a patient with blastoid mantle cell lymphoma harboring a CCND1 rearrangement that progressed despite multiple therapeutic regimens and ultimately transdifferentiated into histiocytic sarcoma. The histiocytic sarcoma demonstrated a CCND1 rearrangement and targeted next-generation sequencing showed a pathogenic variant in NRAS, a gene involved in the RAS/MAPK pathway, known to play a role in the pathogenesis of histiocytic sarcomas. TP53, NOTCH2, CREBBP, and NFKBIE variants were also identified, which are often seen in B-cell lymphomas, while rarely described in histiocytic sarcoma. CONCLUSIONS: To our knowledge, this is the first report to provide evidence for clonal evolution of histiocytic sarcoma from blastoid mantle cell lymphoma based on cytogenic and molecular findings. The patient's protracted therapeutic course may have acted as an evolutionary driver promoting this transdifferentiation process.

Prevalence and types of articulation errors in Saudi Arabic-speaking children with repaired cleft lip and palate.

OBJECTIVES: The purpose of this study was to assess prevalence and types of consonant production errors and phonological processes in Saudi Arabic-speaking children with repaired cleft lip and palate, and to determine the relationship between frequency of errors on one hand and the type of the cleft. Possible relationship between age, gender and frequency of errors was also investigated. METHODS: Eighty Saudi children with repaired cleft lip and palate aged 6-15 years (mean 6.7 years), underwent speech, language, and hearing evaluation. The diagnosis of articulation deficits was based on the results of an Arabic articulation test. Phonological processes were reported based on the productivity scale of a minimum 20% of occurrence. Diagnosis of nasality was based on a 5-point scale that reflects severity from 0 through 4. All participants underwent intraoral examination, informal language assessment, and hearing evaluation to assess their speech and language abilities. The Chi-Square test for independence was used to analyze the results of consonant production as a function of type of CLP and age. RESULTS: Out of 80 participants with CLP, 21 participants had normal articulation and resonance, 59 of participants (74%) showed speech abnormalities. Twenty-one of these 59 participants showed only articulation errors; 17 showed only hypernasality; and 21 showed both articulation and resonance deficits. CAs were observed in 20 participant. The productive phonological processes were consonant backing, final consonant deletion, gliding, and stopping. At age 6 and older, 37% of participants had persisting hearing loss. CONCLUSIONS: Despite early age at time of surgery (mean 6.7 months) for the studied CLP participants in this study, a substantial number of them demonstrated articulation errors and hypernasality. The results showed desirable findings for diverse languages. It is especially interesting to consider the prevalence of glottal stops and pharyngeal fricatives in a population for whom these sound are phonemic.