Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer.

Purpose: We conducted a phase II randomized noncomparative window of opportunity (WOO) trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with olaparib alone or in combination with cisplatin or durvalumab in patients with operable head and neck squamous cell carcinoma (HNSCC). Experimental Design: Forty-one patients with HNSCC were randomized to cisplatin plus olaparib (arm A), olaparib alone (arm B), no treatment (arm C) or durvalumab plus olaparib (arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety, and pathologic complete response (pCR) rate. Paired baseline and resection tumor biopsies and blood samples were evaluated for prespecified biomarkers. Results: A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence. The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients.Programmed death ligand 1 (PD-L1) levels [combined positive score (CPS)] were significantly higher after treatment in arms A and D. Expression of CD163 and colony-stimulating factor 1 receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80, a marker of M1 macrophages, decreased. Conclusion: Preoperative olaparib with cisplatin or alone or with durvalumab was safe in the preoperative setting and led to decrease in Ki67 of at least 25% in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to upregulation of PD-L1 and induction of protumor features of macrophages. Significance: HNSCC is characterized by defective DNA repair pathways and immunosuppressive tumor microenvironment. PARP inhibitors, which promote DNA damage and "reset" the inflammatory tumor microenvironment, can establish an effective antitumor response. This phase II WOO trial in HNSCC demonstrated the immunomodulatory effects of PARP inhibitor-induced DNA damage. In this chemo-naïve population, PARP inhibitor-based treatment, reduced tumor cell proliferation and modulated tumor microenvironment. After olaparib upregulation of PD-L1 and macrophages, suggests that combinatorial treatment might be beneficial. Synopsis: Our WOO study demonstrates that preoperative olaparib results in a reduction in Ki67, upregulation of PD-L1 CPS, and induction of protumor features of macrophages in HNSCC.

Primary Adrenal Lymphomas with Cushing's Syndrome: Two Cases with Evidence of Endogeneous Cortisol Production by the Neoplastic Lymphoid Cells.

Primary adrenal lymphoma (PAL) is a rare entity that presents as unilateral or bilateral rapidly growing adrenal masses, with signs and symptoms most commonly related to adrenal insufficiency due to the mass effect on the surrounding tissues. Although steroeidogenesis has not been previously described in PAL, we herein report two cases of PAL presenting as adrenal incidentalomas (AIs) that demonstrated autonomous cortisol production. A 52-year-old woman presented with lumbar pain; a computed tomography (CT) scan demonstrated a left AI measuring 8.5 × 15 × 10 cm. Similarly, an 80-year-old woman presented with lumbar pain, demonstrating in a CT scan a bilateral AI (right: 9 × 6.5 cm, left: 3.6 × 3.2 cm). Both cases underwent a full hormonal evaluation according to the algorithm for the investigation of AIs, demonstrating increased 24-h cortisol excretion, suppressed fasting adrenocorticotropic hormone (ACTH) levels, and non-suppressed serum cortisol levels in both the overnight and the low-dose dexamethasone suppression tests, indicating autonomous cortisol secretion and Cushing's syndrome. In a relatively short time, both patients developed night sweats, and their clinical picture deteriorated, while the CT scans showed increased dimensions of the masses with radiological characteristics compatible to lymphoma. Both patients underwent ultrasound-guided biopsies (FNBs), revealing infiltration of the left adrenal by diffuse large B-cell lymphoma in the first case, whereas bilateral adrenal infiltration from the same histological type was noted in the second case. Subsequently, they were treated with immunochemotherapy, but the second patient died from an infection shortly after the initiation of the treatment. To our knowledge, this is the first report of PAL presenting with Cushing's syndrome due to autonomous cortisol production, indicating that neoplastic lymphoid cells in PAL might acquire the potential for steroidogenesis; therefore, more cases of PAL should be analyzed so as to further elucidate the complex pathogenesis and the natural course of this entity.

Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and Neck Squamous Cell Carcinoma.

Programmed cell death protein-1 (PD-1)-targeted immunotherapy is approved for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Although its efficacy correlates with PD-L1 expression, response is limited even among positive cases. We employed digital spatial profiling (DSP) to discover potential biomarkers of immunotherapy outcomes in HNSCC. Fifty prospectively collected, pretreatment biopsy samples from patients with anti-PD-1-treated R/M HNSCC, were assessed using DSP, for 71 proteins in four molecularly defined compartments (tumor, leukocyte, macrophage, and stroma). Markers were evaluated for associations with progression-free (PFS) and overall survival (OS). High beta-2 microglobulin (B2M), LAG-3, CD25, and 4-1BB in tumor; high B2M, CD45, CD4 in stroma, and low fibronectin in the macrophage compartment, correlated with prolonged PFS. Improved PFS and OS were observed for cases with high B2M by quantitative and mRNA. Findings were validated in an independent cohort for PFS (HR, 0.41; 95% confidence interval, 0.19-0.93; P = 0.034). B2M-high tumors showed enrichment with immune cell and immune checkpoint markers. Our study illustrates B2M expression is associated with improved survival for immune checkpoint inhibitor (ICI)-treated HNSCC. Significance: In the current study, DSP revealed the positive association of B2M expression in the tumor compartment with immunotherapy outcomes in R/M HNSCC.

Next-generation sequencing (NGS) profiling of matched tumor and circulating tumor DNA (ctDNA) in head and neck squamous cell carcinoma (HNSCC).

OBJECTIVES: The aim of this pilot study was to evaluate the presence of somatic mutations in matched tumor and circulating DNA (ctDNA) samples from patients with primary head and neck squamous cell carcinoma (HNSCC) and assess the association of changes in ctDNA levels with survival. MATERIALS AND METHODS: Our study included 62 patients with stage I-IVB HNSCC treated with surgery or radical chemoradiotherapy with curative intent. Plasma samples were obtained at baseline, at the end of treatment (EOT), and at disease progression. Tumor DNA was extracted from plasma (ctDNA) and tumor tissue (tDNA). The Safe Sequencing System was used assess the presence of pathogenic variants in four genes (TP53, CDKN2A, HRAS and PI3KCA) in both ctDNA and tDNA. RESULTS: Forty-five patients had available tissue and plasma samples. Concordance of genotyping results between tDNA and ctDNA at baseline was 53.3%. TP53 mutations were most commonly identified at baseline in both ctDNA (32.6%) and tDNA (40%). The presence of mutations in this restricted set of 4 genes in tissue samples at baseline was associated with decreased overall survival (OS) [median 58.3 months for patients with mutations vs. 89 months for patients without mutations, p < 0.013]. Similarly, patients presenting with mutations in ctDNA had shorter OS [median 53.8 vs. 78.6 months, p < 0.037]. CtDNA clearance at EOT did not show any association with PFS or OS. CONCLUSIONS: Liquid biopsy enables real-time molecular characterization of HNSCC and might predict survival. Larger studies are needed to validate the utility of ctDNA as a biomarker in HNSCC.

Evidence That Cigarette Smoking Alters Alveolar Type I Cell Nuclear Fractal Dimension.

A large number of alveolar type I and II cells from the lungs of both smokers and non-smokers was collected using 40x magnification histological images from our digital archive. These images underwent a transformation into binary images of nuclear contours, followed by the application of the box-counting method. Statistical analysis revealed a significant difference in the mean box-counting dimension values between type I cells of smokers and non-smokers. However, no significant difference was observed in the mean fractal dimensions of alveolar type II cells. This study provides preliminary evidence of the impact of cigarette smoking on the nuclear shape of alveolar type I cells. Given the high toxicity of cigarette smoke to lung cells and the interconnection between morphology and function, further study is needed to understand its impact on the nuclear shape of these cells. Future research should also explore the effects of second-hand smoke on cell shape.

Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes.

The BM, the major hematopoietic organ in humans, consists of a pleiomorphic environment of cellular, extracellular, and bioactive compounds with continuous and complex interactions between them, leading to the formation of mature blood cells found in the peripheral circulation. Systemic and local inflammation in the BM elicit stress hematopoiesis and drive hematopoietic stem cells (HSCs) out of their quiescent state, as part of a protective pathophysiologic process. However, sustained chronic inflammation impairs HSC function, favors mutagenesis, and predisposes the development of hematologic malignancies, such as myelodysplastic syndromes (MDS). Apart from intrinsic cellular mechanisms, various extrinsic factors of the BM immune microenvironment (IME) emerge as potential determinants of disease initiation and evolution. In MDS, the IME is reprogrammed, initially to prevent the development, but ultimately to support and provide a survival advantage to the dysplastic clone. Specific cellular elements, such as myeloid-derived suppressor cells (MDSCs) are recruited to support and enhance clonal expansion. The immune-mediated inhibition of normal hematopoiesis contributes to peripheral cytopenias of MDS patients, while immunosuppression in late-stage MDS enables immune evasion and disease progression towards acute myeloid leukemia (AML). In this review, we aim to elucidate the role of the mediators of immune response in the initial pathogenesis of MDS and the evolution of the disease.

Systemic Mastocytosis in a Patient with BCR-ABL1-Positive Chronic Myeloid Leukemia in the Remission Phase.

Systemic mastocytosis (SM) comprises a group of rare disorders resulting from tissue infiltration by pathological mast cells. In a percentage ranging from 5 to 40% in various patient series, SM appears to be associated with an accompanying hematologic neoplasm (SM-AHN). The coexistence of SM with chronic myelogenous leukemia (CML) is extremely rare with only 3 cases in the literature. The natural course of CML has changed dramatically over the past 2 decades with the use of tyrosine kinase inhibitors (TKIs). We report a case of diagnosing SM in a patient in complete molecular remission of CML after stopping TKI treatment.

TGF-ß1/Smad Signalling in Proliferative Glomerulonephritis Associated with Autoimmune Diseases.

Glomerulonephritis is a common cause of chronic kidney disease, which has emerged as a major cause of end-stage renal disease. Autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and ANCA-associated vasculitis (AAV) are often associated with proliferative glomerulonephritis. Transforming growth factor-ß1 (TGF-ß1) is a cytokine with pleiotropic effects in chronic renal diseases, based on in vivo and in vitro studies. The Smad-dependent signalling pathway plays an important role in the regulation of renal fibrosis (excessive production of extracellular matrix [ECM]) and inflammation. However, clinical trials targeting TGF-ß1 have presented disappointing results, suggesting that the downstream signalling is quite complex. The diversity of the effects may associate with the interactions between TGF-ß1 signalling and other downstream signalling, as well as the different cellular responses, which TGF-ß1 promotes. Recently, macrophage chemoattract and epigenetic effects have also been identified as new mechanisms, wherefore TGF-ß1/Smad signalling mediates renal injury. This review provides an overview of the role of TGF-ß1/Smad signalling pathway from in vivo and in vitro studies in the pathogenesis of glomerulonephritis and particularly in proliferative glomerulonephritis, which is associated with autoimmune diseases.

Investigation of prognostic biomarkers in patients with urothelial carcinoma treated with platinum-based regimens.

BACKGROUND: Bladder cancer (BC) is a heterogeneous malignancy with dismal outcome. PATIENTS AND METHODS: Mutations in genes, altered or linked to platinum sensitivity in BC, were examined in 66 patients' tumors along with tumor infiltrating lymphocytes (TILs) density and MMR, PD-L1 and CD8 protein expression, as well as basal and luminal subtypes, defined by protein expression of markers, including CK5/6 and GATA3 or CK20, respectively. RESULTS: 41 tumors harbored mutations, mainly in TP53 (38%), ARID1A (17%) and the DNA damage response and repair (DDR) genes ERCC2 (17%) and BRCA2 (15%). Mutations in other DDR relevant genes were also present. Age showed unfavorable prognosis for overall survival (HR=1.07, P = 0.026); no benefit was seen for patients with TP53, ARID1A, ERCC2 or BRCA2 mutations or mutations in 1 or more DDR genes. PD-L1 status positively correlated with stromal (rho=0.46, P < 0.001) and intratumoral (rho=0.53, P < 0.001) CD8 expression or TILs (rho=0.29, P = 0.018); none associated with overall survival (OS). A statistically significant difference was observed between PD-L1 status and immunohistochemistry (IHC)­based subtypes, with tumors classified as luminal (GATA3+ and/or CK20+ and CK5/6-) showing lower PD-L1 expression relative to basal (CK5/6+ and GATA3- and/or CK20-) (median value 0 vs. 2.5, P = 0.029). Concerning OS, no statistically significant difference was seen among patients with basal or luminal tumors. CONCLUSION: No association was seen herein between DDR mutations, TILs, PD-L1, CD8 expression or IHC-based subtypes and patient survival; these observations warrant validation within a larger cohort.

Primary non-Hodgkin lymphoma of the extra-hepatic bile duct: A case report.

Lymphoma is known to be a systemic lymphoproliferative malignancy, which is divided into two subtypes: Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma originates from nodal and extranodal sites. In the staging of non-Hodgkin lymphoma, the liver is implicated in 40% of cases; however, primary liver non-Hodgkin lymphoma represents <1% of all non-Hodgkin lymphoma cases. Because of its rarity, it is not usually considered in the differential diagnosis of patients that present with jaundice. Since the first case of primary non-Hodgkin lymphoma of the extra-hepatic bile ducts was presented, only 42 similar cases have been reported in the English literature. The present case report describes a rare case of non-Hodgkin lymphoma of the common hepatic duct, which presented with obstructive jaundice and represented a complex differential diagnostic issue.

Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer.

Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide. At the time of diagnosis, more than 20% of patients already have metastatic disease. In the last 20 years, the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor, anti-BRAF and antiangiogenics. Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow, proliferate and metastasize. Many molecules are involved in this proangiogenic process, such as vascular endothelial growth factor and its receptors on endothelial cells. A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31, CD34 and CD105 antigens. Even smaller molecules, such as the microRNAs, which are small non-coding RNAs, are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis. In this review, we will discuss recent advances regarding the investigation of angiogenesis, the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+ T cells in the tumor bed. Furthermore, we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.

Pulmonary infection by SARS-CoV-2 induces senescence accompanied by an inflammatory phenotype in severe COVID-19: possible implications for viral mutagenesis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory system can progress to a multisystemic disease with aberrant inflammatory response. Cellular senescence promotes chronic inflammation, named senescence-associated secretory phenotype (SASP). We investigated whether coronavirus disease 2019 (COVID-19) is associated with cellular senescence and SASP. METHODS: Autopsy lung tissue samples from 11 COVID-19 patients and 43 age-matched non-COVID-19 controls with similar comorbidities were analysed by immunohistochemistry for SARS-CoV-2, markers of senescence and key SASP cytokines. Virally induced senescence was functionally recapitulated in vitro, by infecting epithelial Vero-E6 cells and a three-dimensional alveosphere system of alveolar type 2 (AT2) cells with SARS-CoV-2 strains isolated from COVID-19 patients. RESULTS: SARS-CoV-2 was detected by immunocytochemistry and electron microscopy predominantly in AT2 cells. Infected AT2 cells expressed angiotensin-converting enzyme 2 and exhibited increased senescence (p16INK4A and SenTraGor positivity) and interleukin (IL)-1ß and IL-6 expression. In vitro, infection of Vero-E6 cells with SARS-CoV-2 induced senescence (SenTraGor), DNA damage (γ-H2AX) and increased cytokine (IL-1ß, IL-6, CXCL8) and apolipoprotein B mRNA-editing (APOBEC) enzyme expression. Next-generation sequencing analysis of progenies obtained from infected/senescent Vero-E6 cells demonstrated APOBEC-mediated SARS-CoV-2 mutations. Dissemination of the SARS-CoV-2-infection and senescence was confirmed in extrapulmonary sites (kidney and liver) of a COVID-19 patient. CONCLUSIONS: We demonstrate that in severe COVID-19, AT2 cells infected by SARS-CoV-2 exhibit senescence and a proinflammatory phenotype. In vitro, SARS-CoV-2 infection induces senescence and inflammation. Importantly, infected senescent cells may act as a source of SARS-CoV-2 mutagenesis mediated by APOBEC enzymes. Therefore, SARS-CoV-2-induced senescence may be an important molecular mechanism of severe COVID-19, disease persistence and mutagenesis.

Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell-infiltrated tumors. SIGNIFICANCE: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors.This article is highlighted in the In This Issue feature, p. 1.

Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation.

The mechanisms regulating exhaustion of tumor-infiltrating lymphocytes (TIL) and responsiveness to PD-1 blockade remain partly unknown. In human ovarian cancer, we show that tumor-specific CD8+ TIL accumulate in tumor islets, where they engage antigen and upregulate PD-1, which restrains their functions. Intraepithelial PD-1+CD8+ TIL can be, however, polyfunctional. PD-1+ TIL indeed exhibit a continuum of exhaustion states, with variable levels of CD28 costimulation, which is provided by antigen-presenting cells (APC) in intraepithelial tumor myeloid niches. CD28 costimulation is associated with improved effector fitness of exhausted CD8+ TIL and is required for their activation upon PD-1 blockade, which also requires tumor myeloid APC. Exhausted TIL lacking proper CD28 costimulation in situ fail to respond to PD-1 blockade, and their response may be rescued by local CTLA-4 blockade and tumor APC stimulation via CD40L.

Transforming Growth Factor-ß1/Smad Signaling in Glomerulonephritis and Its Association with Progression to Chronic Kidney Disease.

INTRODUCTION: Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-ß/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). METHODS: We evaluated the immunohistochemical expression of TGF-ß1, phosphorylated Smad3 (pSmad3), and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN, and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. RESULTS: TGF-ß1 expression correlated positively with segmental glomerulosclerosis (p= 0.025) and creatinine level at diagnosis (p = 0.002), while pSmad3 expression with interstitial inflammation (p = 0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (p = 0.011), intense interstitial inflammation (p = 0.029), and lower serum complement (C) 3 (p = 0.028) and C4 (p = 0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (p = 0.045) and in podocytes of nonproliferative GN (p = 0.005). Finally, on multivariate Cox-regression analysis, TGF-ß1 expression (hazard ratio = 6.078; 95% confidence interval: 1.168-31.627; p = 0.032) was emerged as independent predictor for CKD. DISCUSSION/CONCLUSION: TGF-ß1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-ß1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.

Metastatic Thyroid Osteosarcoma With Concomitant Multifocal Papillary Carcinoma Presenting as a Collision Tumor.

Metastatic involvement of the thyroid occurs rarely, by either hematogenous spread or direct extension from adjacent organs. The most frequent metastatic tumors are clear cell, renal cell, lung, breast, and squamous cell carcinoma. The occurrence of osteosarcoma and papillary thyroid carcinoma in the same patient is rare, with only a few reported cases in the literature. On the other hand, only one case of osteosarcoma thyroid metastasis has so far been reported. We herewith present another case with metastatic osteosarcoma and multifocal papillary thyroid carcinoma presenting as a collision tumor and review the relevant literature.

Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING.

In this study, we investigate mechanisms leading to inflammation and immunoreactivity in ovarian tumors with homologous recombination deficiency (HRD). BRCA1 loss is found to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammation involving type I interferon (IFN) and stimulator of IFN genes (STING). BRCA1-mutated (BRCA1mut) tumors are thus T cell inflamed at baseline. Genetic deletion or methylation of DNA-sensing/IFN genes or CCL5 chemokine is identified as a potential mechanism to attenuate T cell inflammation. Alternatively, in BRCA1mut cancers retaining inflammation, STING upregulates VEGF-A, mediating immune resistance and tumor progression. Tumor-intrinsic STING elimination reduces neoangiogenesis, increases CD8+ T cell infiltration, and reverts therapeutic resistance to dual immune checkpoint blockade (ICB). VEGF-A blockade phenocopies genetic STING loss and synergizes with ICB and/or poly(ADP-ribose) polymerase (PARP) inhibitors to control the outgrowth of Trp53-/-Brca1-/- but not Brca1+/+ ovarian tumors in vivo, offering rational combinatorial therapies for HRD cancers.

Solitary extramedullary plasmacytoma of the nasopharynx: The role of flow cytometry.

Extramedullary plasmacytoma (EMP) represents a distinct yet rare entity among the plasma cell neoplasms. Given its rarity, no therapeutic consensus has been met. We report the case of a 57-year-old man with a one-year history of nasal congestion and occasional dyspnoea. Imaging showed a hypermetabolic mass in the right nasopharynx extending backward towards the adjacent oropharynx, infiltrating the epiglottis. As incisional biopsy showed histologic and immunophenotypic features consistent with plasma cell neoplasm, whereas the possibility of a marginal zone lymphoma with plasmacytic differentiation was included in the differential diagnosis. A final diagnosis of EMP was reached by using flow cytometry (FC) of a cell suspension from the neoplastic tissue. The patient received local radiotherapy (RT) which resulted to complete remission. In conclusion, flow cytometry might serve as an auxiliary method in cases where immunohistochemistry cannot differentiate between a plasma cell dyscrasia and a B-non-Hodgkin lymphoma. In cases of an established diagnosis of solitary nasopharyngeal EMP RT represents an excellent treatment modality offering prolonged disease-free survival.