A Durable Response to Pembrolizumab in a Patient with Uterine Serous Carcinoma and Lynch Syndrome due to the MSH6 Germline Mutation.

Pembrolizumab, a programmed death 1 ligand (PD-1) checkpoint inhibitor, has elicited responses in mismatch repair (MMR)-deficient advanced solid tumors, leading to its agnostic approval by the US Food and Drug Administration in 2017 when no other therapeutic options are available. However, there are still insufficient data on the response to checkpoint inhibitors in advanced endometrial cancer related to Lynch syndrome (LS) and, specifically, in uterine serous carcinoma, which is uncommon in LS. Here we report a case of metastatic uterine serous carcinoma due to a germline MSH6 mutation (Lynch syndrome) that was discovered because of a patient's tumor MMR deficiency. The patient was started on first-line pembrolizumab in 2018 and sustained a partial response. She remains asymptomatic and progression free for more than 2 years. Tumor sequencing showed a high mutational burden and an upstream somatic mutation in the same gene, p.F1088fs. Immunohistochemical staining was negative for PD-L1 expression. We discuss clinical characteristics of the patient, molecular features of her tumor, and the mechanism of her tumor response. We also discuss the duration of immunotherapy in her case. Our case demonstrated a partial response and a long-term remission from the frontline single-agent pembrolizumab in a woman with metastatic uterine serous carcinoma and Lynch syndrome due to a germline MSH6 gene mutation. Our experience suggests a potential significant clinical benefit of checkpoint inhibitors used as single agents early on in the treatment of MMR-deficient/high microsatellite instability/hypermutated uterine cancers in women with Lynch syndrome. KEY POINTS: Even though checkpoint inhibitors are effective in mismatch repair-deficient endometrial cancer, it is unknown whether the response to them differs between women with endometrial cancer due to germline mutations in a mismatch repair gene (Lynch syndrome) and women with sporadic endometrial cancer. In our case, a patient with Lynch syndrome and recurrent mismatch repair-deficient serous endometrial cancer achieved a durable remission on the first-line therapy with the checkpoint inhibitor pembrolizumab and remains progression free after more than 2 years. Based on our observation and the data, suggesting the stronger immune activation in women with Lynch syndrome-associated endometrial cancer, we propose to use checkpoint inhibitor monotherapy early in the course of their treatment and stratify patients for the presence of Lynch syndrome in clinical trials.

Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.

Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.

Facial Nerve Paraganglioma Masquerading as Bell palsy: A Reconstructive Pitfall.

BACKGROUND: Facial paralysis can drastically diminish satisfaction in one's social interactions and overall quality of life. Bell palsy is the most common cause of facial palsy, however, a diagnosis of "atypical" BP may originate from an entirely different pathological process. This case highlights a rare case of facial nerve paraganglioma, initially misdiagnosed as BP, that resulted in facial paralysis from neoplastic invasion of the facial nerve. CASE PRESENTATION: A 66-year old Hispanic woman with systemic lupus erythematosus presented to the plastic surgery clinic with complaints of drooling and being unable to smile. She experienced several episodes of left facial paralysis and was diagnosed with BP at an outside institution. Each episode was only partially responsive to steroid therapy. Imaging at our institution demonstrated lobulated enhancement along the vertical and extratemporal segments of the facial nerve, which prompted surgical intervention. The patient underwent left transmastoid approach for removal of the lesion involving the facial nerve followed by facial nerve reanimation via gracilis free flap without complication. CONCLUSIONS: This report outlines an extraordinarily rare case of a patient with facial nerve paraganglioma. This case represents the importance of reconstructive surgeons in considering a thorough diagnostic work-up with imaging and histopathology in the setting of idiopathic facial paralysis. Successful collaboration between otolaryngology and plastic surgery made streamlined diagnosis and surgical treatment of this unique case possible.

Indoleamine 2,3-Dioxygenase-1 Expression in Adrenocortical Carcinoma.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO-1) is overexpressed in many human carcinomas and a successful target for therapy in mouse models. Prognosis of patients with advanced adrenocortical carcinoma (ACC) is poor due to the lack of effective treatments, and new therapies are therefore needed. Herein, we investigate whether IDO-1 is expressed in human ACC tissues. METHODS: 53 tissue samples from patients with ACC, adrenal adenoma (AA), adrenocortical tumors (ACTs), and normal adrenal were identified. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded slides for IDO-1. Samples were scored for cytoplasmic staining as per intensity and the percent of positive cells and for stromal staining by percent of positive cells. Tumor characteristics, PD-L1, PDL-2, and CD-8+ T-lymphocyte expression were also determined. RESULTS: Samples from 32 ACC, 3 ACT, 15 AA, and 3 normal adrenal were analyzed. IDO-1 was expressed in tumor tissue in 22 of 32 ACC samples, compared with 8 of 15 AA sample (P = 0.344). IDO-1 expression was significantly increased in stromal tissue of ACC samples (16 of 33), compared with AA samples (0 of 15) (P = 0.001). IDO-1 expression in ACC and AA samples was associated with PD-L2 expression (P = 0.034). IDO-1 expression in ACC stromal tissue was associated with CD8+ T-lymphocyte infiltration (P = 0.028). CONCLUSIONS: IDO-1 is expressed in a majority of ACC samples. Its expression in tumor tissue is associated with PD-L2 expression, and expression in stroma is associated with CD8+ cell infiltration. IDO-1 inhibition, alone or in combination with PD-1 inhibition, could therefore be an interesting target in treatment of ACC.

Slowly progressive facial paralysis: Intraneural squamous cell carcinoma of unknown primary.

BACKGROUND: In this report, we present a unique case of intraneural squamous cell carcinoma of unknown primary found within the facial nerve and the proposed algorithms for diagnosis and management of progressive idiopathic facial paralysis. CASE PRESENTATION: A 66-year-old female with a previous history of basal cell carcinoma presented with right-sided progressive facial paralysis. Repeated magnetic resonance imaging as well as targeted workup failed to reveal a diagnosis. 20 months following symptom onset, after the patient's facial function slowly progressed to a complete paralysis, repeat magnetic resonance imaging revealed enhancement at the stylomastoid foramen. The patient underwent superficial parotidectomy, transmastoid facial nerve decompression and resection of descending and proximal extratemporal facial nerve segments, as well as great auricular nerve interposition grafting. Intraoperatively, frozen sections from the surface of the facial nerve, and the proximal and distal segments of the facial nerve following resection, were negative for malignancy. The final pathology revealed infiltrating poorly differentiated squamous cell carcinoma of the facial nerve with negative margins. CONCLUSION: In cases of slowly progressive facial paralysis the clinician needs to consider malignancy until proven otherwise. Without an identifiable primary malignancy, early algorithmic assessment of presenting characteristics may facilitate expedited clinical decision making and surgical management of malignancy involving the facial nerve. In cases of slowly progressive facial paralysis, when the time comes for surgical exploration and biopsy, head and neck surgeons must be aware that malignancy can exist entirely within the facial nerve, without pathologic changes on the surface of the nerve or in the surrounding tissue.

Misdiagnosis of Li-Fraumeni Syndrome in a Patient With Clonal Hematopoiesis and a Somatic TP53 Mutation.

Li-Fraumeni syndrome (LFS) is a rare genetic disorder that confers a high risk of developing certain malignancies at a young age. It is caused by germline mutations in the TP53 gene and is typically diagnosed by sequencing this gene in blood cells. The presence of a mutation in approximately half of the DNA reads (allelic fraction of 50%) is an indicator of a germline mutation, such as that in LFS. Clonal hematopoiesis (CH) is an expansion of a hematopoietic clone containing a somatic driver mutation with a low allelic fraction, usually not more than 10% to 20%. This report presents a patient with fallopian tube carcinoma who underwent multigene panel testing for cancer predisposition and was found to have a mutation in the TP53 gene, c.733G>T (p.Gly245Cys). Since the TP53 mutation had an allelic fraction of approximately 50%, it was interpreted as being germline, and the patient was diagnosed as having LFS. A year later, she developed acute myelogenous leukemia. Subsequent mutational analysis showed that the TP53 mutation was absent in her benign tissue sample but present in leukemic cells. Furthermore, sequencing of the fallopian tube tumor tissue revealed a different TP53 gene mutation, c.818G>T (p.Arg273Leu). These observations confirmed that the previously identified mutation in her blood was somatic rather than germline and that she had CH at the time of genetic testing. CH can occasionally lead to a misdiagnosis of a germline mutation and a cancer predisposition syndrome that has significant implications for patients and their families. Therefore, the abnormal result of genetic testing for hereditary cancer susceptibility should be carefully interpreted when the clinical presentation is atypical, when the patient is older, when the gene in question is known to have potential germline and somatic mutations such as the TP53 gene, and when the allelic fraction is approximately 50%.

Lowering positive margin rates at radical prostatectomy by color coding of biopsy specimens to permit individualized preservation of the neurovascular bundles: is it feasible? a pilot investigation.

OBJECTIVE: To evaluate whether color-coding of prostate core biopsy specimens aids in preservation of the neurovascular bundles from an oncological perspective. MATERIALS AND METHODS: MRI guided transrectal ultrasound and biopsy of the prostate were performed in 51 consecutive patients suspected of being at high risk for harboring prostate cancer. Core specimens were labeled with blue dye at the deep aspect and red dye at the superficial peripheral aspect of the core. The distance from the tumor to the end of the dyed specimen was measured to determine if there was an area of normal tissue between the prostate capsule and tumor. RESULTS: Of the 51 patients undergoing prostate biopsy, 30 (58.8%) were found to have cancer of the prostate: grade group 1 in 13.7%, 2 in 25.5%, 3 in 7.8%, 4 in 7.8% and 5 in 3.9% of the cohort. A total of 461 cores were analyzed in the cohort, of which 122 showed cancer. Five patients opted to undergo robotic assisted laparoscopic radical prostatectomy. No patients had a positive surgical margin (PSM) or extra prostatic extension (EPE) on radical prostatectomy if there was a margin of normal prostatic tissue seen between the dye and the tumor on prostate biopsy. CONCLUSION: Color-coding of prostate biopsy core specimens may assist in tailoring the approach for preservation of the neurovascular bundles without compromising early oncological efficacy. Further study is required to determine whether this simple modification of the prostate biopsy protocol is valuable in larger groups of patients.

Mastitis, a Radiographic, Clinical, and Histopathologic Review.

Mastitis is a benign inflammatory process of the breast with heterogeneous histopathological findings, which clinically and radiographically may mimic a mammary carcinoma. We undertook a retrospective study on 37 cases of mastitis in our institution to correlate the radiographic imaging features and the clinical presentation with the histopathological findings. Histologically, there were 21 granulomatous, 7 fibrous, 3 plasma cell, 3 lupus, 2 lymphocytic, and 1 case of acute mastitis. Radiographically, 16/25 (64%) patients with ultrasound studies showed irregular hypoechoic masses suspicious for malignancy. Clinically, 38% of patients had an associated systemic disease.

Hypofractionated radiation in secretory breast cancer: A case report.

Secretory carcinoma is a rare and indolent breast cancer with a lack of established treatment paradigms. We describe a case of a woman who underwent breast conservative therapy in the modern era. A 48 year old woman with a screen-detected left breast cancer was found to have early-stage secretory carcinoma after definitive breast conservation surgery. Further management with adjuvant radiation was recommended. After definitive breast conservative surgery, final pathology was notable for secretory breast carcinoma due to the immunohistologic characteristics of the tumor, ETV6-NTRK3 gene fusion, and histologic findings. After multi-disciplinary discussion, it was recommended that the patient proceed with adjuvant radiation. She was treated using a modestly hypofractionated regimen of 4256 cGy in 16 fractions. She tolerated the treatment well, developing only grade 1 radiation dermatitis. At 1 year follow-up she was clinically and radiographically free of disease. With a shift in management toward breast conservative therapy, defining the role of adjuvant radiation for secretory carcinomas in the modern era is of increasing importance. Modestly hypofractionated radiation is well-tolerated. Oncologic outcomes will be assessed with continued long-term follow-up.

Is Regional Lymph Node Metastasis of Head and Neck Paraganglioma a Sign of Aggressive Clinical Behavior: A Clinical/Pathologic Review.

BACKGROUND: Head and neck paraganglioma is a rare neoplasm of the paraganglia. It accounts for <1% of all head and neck tumors. It usually has benign clinical course; however, malignant paraganglioma can only be diagnosed by showing metastatic disease. We undertook a retrospective study to assess the clinical significance of regional lymph nodes metastases in head and neck paragangliomas. DESIGN: From 1993 to 2016, primary head and neck paragangliomas are identified. The patient clinical and histopathologic materials were reviewed. RESULTS: Sixty-five specimens from 62 patients (3 patients with more than 1 specimens) with head and neck paragangliomas were recorded (49 female and 13 males) with mean age of 54 (24-78 years). The locations of the tumors were as follows: carotid body: 30, glomus tympanicum: 11, glomus jugulare: 14, parapharyngeal space: 3, and 1 case each of larynx, skull base, paraglottic area, infratemporal fossa, mastoid, cerebellopontine (CP) angle, and pyriform sinus. On histopathology, we found 5 cases of sclerosing variant. Thirty-two (52%) of the 62 patients had regional lymph node biopsy. Four (12%) of the 32 show metastatic paraganglioma (3 females and 1 male with mean age = 35). Two of the 5 cases of sclerosing variant had positive lymph nodes. No evidence of local recurrence or distant metastasis in the patients with positive lymph nodes with a 6 to 11 years follow-up. One of the 28 patients with negative lymph nodes developed metastatic disease to lumbar spine in 5 years. CONCLUSION: Metastatic paraganglioma to regional lymph nodes may have indolent clinical behavior, with disease-free survival of up to 11 years. The incidence of metastatic disease in lymph nodes was 4 (12%) of 32. Forty percent (2/5) of the cases with sclerosing variant of paraganglioma had lymph node metastases indicating that this tumor may have a more aggressive histological behavior.

Endometrial Sarcoma Metastasis to the Pterygopalatine Fossa: A Case Report and Review of the Literature.

Metastatic skull base malignancies infrequently occur but, when present, typically arise from breast malignancies. Pterygopalatine fossa (PPF) metastasis of any malignancy is further seldom reported, and metastasis of gynecologic malignancies to the PPF has not been previously described in the literature. We present a single case of a 42-year-old female with the first likely case of high-grade endometrial sarcoma metastatic to the PPF. The patient presented with facial pain and numbness in the V2 distribution presented for evaluation. History was significant for several months of dysmenorrhea and metrorrhagia. Computed tomography, magnetic resonance imaging, and positron emission tomography imaging revealed a PPF mass with local extension and bony metastases. Endoscopic biopsy was performed, and final pathology was most consistent with metastatic high-grade endometrial stromal sarcoma. This is the first reported case of likely metastatic endometrial sarcoma to the PPF. This case report highlights the possibility of rare distant metastasis of gynecologic malignancy to this area of the skull base.

Inter-pathologist Agreement on Structured Histopathology Reporting in Chronic Rhinosinusitis.

BACKGROUND: Structured histopathology reporting is increasingly being utilized in rhinology to characterize endotypes in chronic rhinosinusitis and guide management decisions after sinus surgery. OBJECTIVE: The goal of this investigation is to evaluate inter-observer agreement in structured histopathology reporting. METHODS: Two experienced head and neck pathologists independently compiled structured histopathology reports for tissue samples collected during functional endoscopic sinus surgery. Cohen's standard kappa (κ) coefficients were calculated for each histopathologic variable to assess inter-pathologist agreement. RESULTS: A total of 92 cases were analyzed. Substantial inter-pathologist agreement was reached on tissue eosinophil count (κ = 0.64, P < .001), the presence of eosinophil aggregates (κ = 0.62, P < .001), and the presence of fungal elements (κ = 0.74, P < .001). There was moderate agreement on the degree of inflammation (κ = 0.56, P < .001) and the presence of squamous metaplasia (κ = 0.46, P < .001). There was fair agreement on the presence of neutrophil infiltrates (κ = 0.33, P < .001), the presence of hyperplastic changes (κ = 0.40, P < .001), and the presence of fibrosis (κ = 0.24, P = .022). There was only slight agreement on the degree of subepithelial edema (κ = 0.20, P = .008). The κ coefficients for basement membrane thickening and mucosal ulceration were not statistically significant. CONCLUSION: High inter-pathologist agreement was demonstrated for several salient histopathologic variables, including tissue eosinophil count and the presence of eosinophil aggregates. However, refining the definitions of certain histopathologic variables may improve the reproducibility of structured histopathology reporting.

Acinic cell carcinoma of the salivary gland associated with lymphoid-rich stroma. A diagnostic dilemma on cytology: Study of two cases.

A lymphoid-rich stroma is a common finding in salivary gland tumors. Several reports documented this association with acinic cell carcinoma (ACC). However, cytologic studies reporting this phenomenon are rare and mainly confined to sporadic single case reports. We present the cytologic features of two cases of ACCs of the parotid gland displaying a lymphoid-rich background and discuss the cytologic differential diagnoses of this uncommon ACC variant.

Fine needle aspiration of an intrathyroidal parathyroid carcinoma mimicking a primary thyroid anaplastic carcinoma: A case report with review of the literature.

Intrathyroidal parathyroid carcinoma is an uncommon malignancy. A 46-year-old male presented with a left neck mass. Computed tomography (CT) scan revealed a hypodense mass in the left thyroid lobe along with evidence of metastatic lymphadenopathy. Aspiration of the left thyroid nodule was performed, and a diagnosis of malignancy was rendered, favoring a primary anaplastic carcinoma. Based on the cytologic diagnosis, the patient underwent a total thyroidectomy. Before the surgery, intact parathyroid hormone (PTH) and calcium level (PTH = 78 pg/mL; Calcium = 10.6 mg/dL) were found to be minimally elevated. On gross examination, a 3.2 cm mass within the left inferior thyroid lobe was seen. Histopathologic examination and ancillary studies supported the diagnosis of a parathyroid carcinoma. We, hereby present, an exceedingly rare presentation of an intrathyroidal parathyroid carcinoma with only minimal elevation of PTH and calcium, mimicking a primary anaplastic thyroid carcinoma on cytologic examination.

Histopathologic Influences of Comorbid Smoking Status in Chronic Rhinosinusitis.

BACKGROUND: Smoking status has been established as a known irritant of the upper and lower respiratory tracts, leading to inflammation throughout the respiratory system. Tobacco smoking is one comorbidity encountered among chronic rhinosinusitis (CRS) patients. The histopathologic features of CRS and comorbid smoking status have yet to be determined by structured histopathology and may have important implications on disease management. METHODS: Retrospective study of structured histopathology reports analyzing sinus tissue removed during functional endoscopic sinus surgery. Histopathology variables were compared among patients with CRS who were reported as never smokers, former smokers, or current smokers. RESULTS: A total of 285 CRS patients were included: 173 never smokers, 85 former smokers, and 27 current smokers. When compared with former smokers, current smokers demonstrated increased basement membrane thickening (88.9% vs 67.1%, P <.020). Compared with never smokers, former and current smokers collectively demonstrated increased hyperplastic changes (14.3% vs 6.9%, P < .035), increased squamous metaplasia (26.8% vs 17.3%, P < .040), and trends toward increased basement membrane thickening (72.3% vs 65.3%, P < .124) and increased fibrosis (47.3% vs 40.5%, P < .154). CONCLUSION: Smoking status may influence histopathologic tissue-level changes in CRS disease. Interestingly, former and current smokers maintained few differences in histopathology. However, former and current smokers collectively demonstrated increased chronic inflammatory changes compared with never smokers. These findings suggest that the timing of smoking exposure has limited effect on the tissue level, rather exposure overall influences inflammatory change. These findings may have important implications on medical and surgical management of CRS disease and comorbid smoking status.

Rare infection in patient with rheumatoid arthritis treated with adalimumab.

Mycobacterium haemophilum is a rare pathogen, predominately present in the immunocompromised population. It is especially studied in HIV and haematological malignancy patients. Given its unique living conditions, it is often difficult to establish its diagnosis, but it is often suspected by its classic association with ulcerating skin findings. Our case is unique in that our patient is immunocompromised by his rheumatoid arthritis treatment, and presented without any skin lesions, but was found to have this rare pathogen causing a constellation of unusual symptoms.

Hypercalcemia in Metaplastic Squamous Cell Carcinoma of the Breast.

BACKGROUND Metaplastic breast carcinoma is a rare entity characterized by rapid growth and heterogeneous histological features. It comprises less than 1% of all breast cancers, and no definitive treatment has yet been identified. CASE REPORT We describe here a patient who presented with acute hypercalcemia and was found to have a large ulcerated breast mass. Once the patient's hypercalcemia was stabilized, she underwent complete surgical resection that revealed a large, cavitary, necrotic mass measuring over 11 cm. The final surgical pathology revealed metaplastic carcinoma with extensive squamous differentiation and ductal carcinoma in situ. At the request of her family, no additional treatment was pursued. CONCLUSIONS While there is not a significant body of data on the pathogenesis of metaplastic breast carcinoma, it is typically hormone receptor negative and has a variable response to chemotherapy. Surgical excision is the most commonly pursued treatment.

Correlation of p16 Expression on Cancer and Stromal Cells With Clinicopathologic and Immunohistochemical Features of Lobular Breast Carcinoma.

BACKGROUND: Cancer-associated fibroblasts, play a central role in the tumor-stroma interaction and promote tumorigenesis. However, it is still unclear how these processes are regulated. The aim of this study is to investigate p16 expression in cancer and stromal cells of invasive lobular carcinoma (ILC). DESIGN: Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor, E-cadherin, and human epidermal growth factor receptor 2 of 70 ILC cases were retrieved. In addition, immunohistochemical were performed for p53, p16, and cyclin D1. The p16 expression in cancer and stromal cells were correlated with different clinicopathologic parameters. RESULTS: Of the 70 cases, 8 cases were p16- cancer and stromal cells, 14 cases p16- cancer and p16+ stromal cells, 14 cases p16+ cancer and p16- stromal cells, and 34 cases p16+ cancer and stromal cells. Thirty-one of the 59 cases showed axillary lymph node metastases. Nodal involvement, recurrence, and metastasis of ILC with p16+ cancer cells and p16- stromal cells were more frequent compared with other groups. ILC with p16+ cancer and p16- stromal cells were frequently negative for ER, progesterone receptor, and cyclin D1, p53 positive and triple negative compared with other groups. There was no recurrence and metastasis in ILC with p16- cancer and p16+ stromal cells. ILC with p16+ cancer and stromal cells were significantly node negative and were positive for ER and cyclin D1 compared with other groups. CONCLUSIONS: ILC with p16+ cancer and p16- stromal cells were characterized by frequent nodal involvement, recurrence, and metastatic propensity. These results suggest that p16, has novel anticancer properties capable of suppressing cancer cell migration and invasion and pharmacologic restoration of p16 level in stromal fibroblasts may be exploited as therapeutic strategy to prevent nodal or distant metastasis.

The presence of eosinophil aggregates correlates with increased postoperative prednisone requirement.

OBJECTIVES/HYPOTHESIS: Failure after sinus surgery is multifactorial, but often due to recurrence of inflammatory mucosal disease. Postoperative steroid requirements for controlling mucosal inflammation may provide insight into predicting which patients require more aggressive medical therapy to prevent disease relapse. STUDY DESIGN: Retrospective chart review. METHODS: A review was performed of patients who underwent functional endoscopic sinus surgery (FESS) for refractory chronic rhinosinusitis (CRS). Sino-Nasal Outcome Test-22 scores and cumulative prednisone dose (milligrams) requirements at 1, 3, and 6 months postoperatively were reviewed. A structured histopathology report of 11 variables was accessed to correlate histopathology with postoperative steroid requirements. RESULTS: One hundred one patients were reviewed including 42 CRS with nasal polyps and 59 CRS without nasal polyps patients. CRS patients with eosinophilia required greater cumulative steroids to control disease at 1-, 3-, and 6-month postoperative intervals (P < .026, P < .007, P < .013, respectively) compared to patients without eosinophilia. Patients with tissue eosinophil aggregates required the highest cumulative steroids at 1-, 3-, and 6-month postoperative intervals (P < .003, P < .001, P < .001, respectively). When removing patients with eosinophil aggregates from the eosinophilia group, no difference persisted between patients with eosinophilia and those without eosinophilia at all intervals (P = .664, P = .735, P = .800, respectively). No other histopathology variable correlated with postoperative steroid requirement. CONCLUSIONS: Tissue eosinophil aggregates appear to be the largest driving factor for increased prednisone requirements after sinus surgery to control mucosal disease than mere presence of eosinophils. This key finding may identify patients at high risk for failure after sinus surgery and guide more proactive postoperative management. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:794-799, 2019.

The impact of race and insurance status on baseline histopathology profile in patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease process characterized by different phenotypes and histopathology profiles. Race and access to care have been implicated in CRS disease severity. Structural histopathology reporting may aid in delineating the inflammatory burden responsible for this effect. METHODS: A structured histopathology report of 14 variables was utilized to assess sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared by race (Black, White, Latino, and Asian) and insurance status (Medicare, Medicaid, and private insurance). RESULTS: A total of 201 CRS patients (124 White, 38 Black, 28 Latino, and 9 Asian) undergoing FESS were included. Black patients demonstrated increased SNOT-22 scores (50.74 ± 20.32 vs 41.47 ± 22.75, p < 0.022) and number of eosinophils per high-power field (>5/HPF) (60.5% vs 44.8%, p < 0.05). White patients demonstrated decreased eosinophil aggregates (22.6% vs 35.1%, p < 0.039) and eosinophils/HPF (<5/HPF) (42.7% vs 55.8%, p < 0.048). Medicaid patients showed increased SNOT-22 score (55.50 ± 24.46 vs 41.39 ± 21.74, p < 0.003), polypoid disease (61.5% vs 42.3%, p < 0.05), subepithelial edema (80.8% vs 53.1%, p < 0.006), hyperplastic/papillary changes (23.1% vs 8.0%, p < 0.028), fibrosis (61.5% vs 38.5%, p < 0.036), eosinophil aggregates (46.2% vs 24.6%, p < 0.022), and eosinophils/HPF (>5/HPF) (65.4% vs 45.1%, p < 0.043). When controlling for insurance status, Black race was no longer associated with increased SNOT-22 (p < 0.104) or eosinophils/HPF (>5/HPF) (p < 0.183). CONCLUSION: Black and Medicaid patients demonstrated more severe disease by histopathology and SNOT-22 scores. These findings were no longer significant among Black patients after adjusting for insurance status, suggesting that the prevailing factor influencing worse disease may be access to care.