Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), continues to be one of the most prevalent infectious diseases in the world. There is an upward trend in occurrence due to emerging multidrug resistant strains and an increasingly larger proportion of immunocompromised patient populations as a result of the acquired immunodeficiency syndrome pandemic. The complex and often deadly combination of multidrug resistant M. tb (MDR-M. tb) along with human immunodeficiency virus (HIV) puts a significant number of people at high risk for pulmonary and extra-pulmonary TB without sufficient therapeutic options available. Natural killer (NK) cells and macrophages are major components of the body’s innate immune system, contributing significantly to the body’s ability to synergistically inhibit the growth of M. tb in immune compromised individuals lacking a sufficient T cell response. Direct mechanisms of control are largely through the secretory products perforin, granulysin, and granzymes, as well as multiple membrane-bound death receptors that facilitate target directed lysis. NK cells also have a role in indirectly stimulating an immune response through activation of macrophages and monocytes with multiple signaling pathways, including both reactive oxygen species and reactive nitrogen species. Glutathione (GSH) has been shown to play a part in inhibiting the growth of intracellular M. tb through bacteriostatic mechanisms. Enhancing cellular GSH through several cytokines and N-acetyl cysteine has been shown to increase these effects, at least in part, through their action on NK cells. Taken together, there is substantial evidence for a mechanistic correlation between NK cell activity and functionality in combating M. tb in HIV infection mediated through adequate GSH production and use.

RhoB, a member of the Ras homolog gene family and GTPase, regulates intracellular signaling pathways by interfacing with epidermal growth factor receptor (EGFR), Ras, and phosphatidylinositol 3-kinase (PI3K)/Akt to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. Functionally, RhoB, part of the Rho GTPase family, regulates intracellular signaling pathways by interfacing with EGFR, RAS, and PI3K/Akt/mammalian target of rapamycin (mTOR), and MYC pathways to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. RHOB expression has a complex regulatory backdrop consisting of multiple histone deacetyltransferase (HDACs 1 and 6) and microRNA (miR-19a, -21, and -223)-mediated mechanisms of modifying expression. The interwoven nature of RhoB’s regulatory impact and cellular roles in regulating intracellular vesicle trafficking, cell motion, and the cell cycle lays the foundation for analyzing the link between loss of RhoB and tumorigenesis within the context of age-related decline in RhoB. RhoB appears to play a tissue-specific role in tumorigenesis, as such, uncovering and appreciating the potential for restoration of RHOB expression as a mechanism for cancer prevention or therapeutics serves as a practical application. An in-depth assessment of RhoB will serve as a springboard for investigating and characterizing this key component of numerous intracellular messaging and regulatory pathways that may hold the connection between aging and tumorigenesis.

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Introduction/Objective Follicular dendritic cell sarcoma (FDCS) is the malignant counterpart of the germinal center follicular dendritic cell. Cytomorphological descriptions are few, with only 24 prior cytology reports from 22 publications. We present 4 cases with the aim of adding to this small body of literature. Methods Our database was searched for “dendritic cell.” Patients diagnosed with FDCS that had a cytology specimen were included. Clinical and cytologic features were tabulated. Results Case 1 was an 87-year-old man with a retroperitoneal mass. Aspiration rendered a new diagnosis of FDCS, supported cell block immunohistochemistry. Case 2 was an aspiration of metastatic FDCS to the lung in a 40 year-old- man with a known neck primary. Case 3 was a 46-year-old-man with a left neck mass. Aspiration rendered a misdiagnosis of “atypical epithelioid cells in a background of granulomatous inflammation”. Subsequent needle biopsy confirmed FDCS. Case 4 was an aspiration of metastatic FDCS to the liver in a 66 year-old-woman with a known splenic primary. Comparison of cytomorphology show identical features in all cases. Smears were hypercellular and composed of variably sized syncytial aggregates as well as individually dispersed cells. Tumor cells were variably epithelioid to spindled, had fine chromatin and small nucleoli, displayed frequent bi- and multinucleated forms, and had abundant pale cytoplasm with long, slender fibrillar processes. All cases demonstrated many small lymphocytes intermixed both within the syncytial aggregates and dispersed in the background. Conclusion Cytomorphological features of FDCS appear conserved from case to case. Knowledge of these features may aid in its recognition in aspiration material.