A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH.

BACKGROUND AND AIMS: Manual histological assessment is currently the accepted standard for diagnosing and monitoring disease progression in NASH, but is limited by variability in interpretation and insensitivity to change. Thus, there is a critical need for improved tools to assess liver pathology in order to risk stratify NASH patients and monitor treatment response. APPROACH AND RESULTS: Here, we describe a machine learning (ML)-based approach to liver histology assessment, which accurately characterizes disease severity and heterogeneity, and sensitively quantifies treatment response in NASH. We use samples from three randomized controlled trials to build and then validate deep convolutional neural networks to measure key histological features in NASH, including steatosis, inflammation, hepatocellular ballooning, and fibrosis. The ML-based predictions showed strong correlations with expert pathologists and were prognostic of progression to cirrhosis and liver-related clinical events. We developed a heterogeneity-sensitive metric of fibrosis response, the Deep Learning Treatment Assessment Liver Fibrosis score, which measured antifibrotic treatment effects that went undetected by manual pathological staging and was concordant with histological disease progression. CONCLUSIONS: Our ML method has shown reproducibility and sensitivity and was prognostic for disease progression, demonstrating the power of ML to advance our understanding of disease heterogeneity in NASH, risk stratify affected patients, and facilitate the development of therapies.

Endovascular temporary vessel occlusion with a reverse-thermosensitive polymer for bloodless minimally invasive renal surgery.

PURPOSE: To demonstrate the feasibility of reversible vessel embolization with angiographic guidance for delivery of a rapid reverse-thermosensitive polymer to provide hemostasis as an aid for minimally invasive renal surgery in a porcine model. MATERIALS AND METHODS: After isolation of the left kidney of seven anesthetized pigs (50-70 kg) with a surgical robot, a renal angiogram of both kidneys was obtained. A 5-F angiographic catheter was used to selectively embolize a lower-pole segmental artery of the right and left kidney with a thermosensitive polymer (LeGoo-XL). Distal and proximal embolization of the target vessel was compared. Degree and duration of hemostasis and reversibility was determined. After complete hemostasis was obtained angiographically, a partial robotic lower-pole nephrectomy was performed on the left kidney only. RESULTS: Only proximal embolization provided controllable hemostasis. A 20% polymer concentration in a buffer solution of 40% saline solution and 40% iodine contrast medium by weight injected at room temperature resulted in a reproducible embolus for more than 30 minutes, the time needed to perform a partial nephrectomy. The radiographic appearance of the embolus was used to determine the total amount of polymer needed. Cold saline solution completely dissolved any residual polymer at the end of surgery. CONCLUSIONS: Proximal arterial occlusion with a thermosensitive polymer can be rapidly reversed with selective intraarterial infusion of chilled saline solution. Preceding nephron-sparing surgery with transcatheter embolization of the relevant branch of the renal artery with the polymer can facilitate the procedure and ought to be investigated further.

Living donor liver transplantation for hepatocellular carcinoma: Increased recurrence but improved survival.

In regions with a limited deceased donor pool, living donor adult liver transplantation (LDALT) has become an important treatment modality for patients with hepatocellular carcinoma (HCC) and cirrhosis. Studies have shown higher recurrence rates of HCC after LDALT in comparison with deceased donor liver transplantation (DDLT). The aim of our study was to examine the outcome results and recurrence rates for patients with HCC who underwent LDALT at our center. During an 8-year period, 139 patients underwent LDALT, of whom 28 (20.1%) had HCC in their explanted livers. The median follow-up was 40.8 months. The mean explant tumor size was 3.3 +/- 1.2, and the mean number of tumors was 1.5 +/- 0.8. Twenty-one patients (75%) had tumors within the Milan criteria, 5 patients had tumors outside the Milan criteria but within the University of California San Francisco (UCSF) criteria, and 2 patients were beyond the UCSF criteria. The overall 1- and 5-year patient and graft survival rates were 96% and 81%, respectively. Survival following LDALT was significantly better than survival following DDLT for HCC during the same time period (P = 0.02). Eight patients (28.6%) developed tumor recurrence. Poor differentiation of tumor cells was the most significant determinant of recurrence. Despite high recurrence rates of HCC following LDALT, overall 5-year survival appears to be excellent.

Approach to diagnosis of auto-immune hepatitis.

Auto-immune hepatitis (AIH) is one of the chronic liver diseases, seen predominantly in women, resulting from dysregulated immune mechanisms not yet clearly defined. Based on a combination of clinical and laboratory parameters with both positive and negative weights, the International AIH Group devised a scoring system in 1993. The system was modified in 1999 and has proven useful for both diagnostic and research purposes. This review deliberates on the clinical, immunological and histological features of this entity.

Post-liver transplant cholestatic disorder with biliary strictures: de novo versus recurrent primary sclerosing cholangitis.

Cholestatic allograft dysfunction following liver transplantation (LT) can result from many different underlying pathogenetic mechanisms and is a major cause of morbidity and graft loss. Although recurrence of primary sclerosing cholangitis (PSC) is a described entity following LT, the diagnosis is difficult and requires exclusion of common risk factors for stricture formation. There are no reports in the literature of de novo PSC arising in a patient who did not have that disease prior to transplantation. Reported herein is the case of a patient who underwent transplantation for end-stage cryptogenic cirrhosis and who had no underlying risk factors, but who developed late post-LT cholestatic disorder with non-anastomotic biliary strictures. The combined clinical, radiological, and pathological findings resembled those of PSC. Admittedly, it is a challenging proposition but the possibility of a de novo PSC-like syndrome in this patient is raised. A recurrence in a patient who may have had a burnt-out, PSC-like syndrome presenting as cryptogenic cirrhosis, however, cannot be entirely excluded.

Methasteron-associated cholestatic liver injury: clinicopathologic findings in 5 cases.

BACKGROUND & AIMS: Methasteron is a nutritional supplement used to increase weight or accelerate the build-up of muscle mass. The aim of this study was to describe 5 cases of hepatotoxicity in patients using methasteron seen at tertiary-care medical centers. METHODS: A case report design was used. RESULTS: Five previously healthy patients who used methasteron developed jaundice 2 weeks after discontinuation; they presented to a tertiary-care medical center 2 weeks later. Within another 2 to 3 weeks, bilirubin levels peaked. About 12 weeks after initial presentation, all cases resolved with no identifiable residual hepatic dysfunction. CONCLUSIONS: Methasteron use can result in severe hepatotoxicity. Liver failure can worsen after initial presentation, especially within 2 weeks. With close observation and supportive care, acute hepatic injury should resolve.

Patterns of recurrent hepatitis C after liver transplantation in a recent cohort of patients.

Clinicopathologic trends of recurrent hepatitis C after liver transplantation (LT) in hepatitis C (HCV) patients seem to have changed in recent years. Our aims were to define the current post-LT patterns of HCV recurrence and identify features of diagnostic and/or prognostic significance. Detailed analysis was performed on 92 HCV patients who underwent LT from June 1999 to December 2003 and survived early post-LT period. The study patients were grouped, as follows: no histologic recurrence (n = 31), "typical" recurrent HCV (n = 52), and post-LT autoimmune-like hepatitis ("AIH-like") (n = 9). The typical and AIH-like groups had mostly common features with post-LT progressive fibrosis (stage > or =2) more frequent in the latter. Based on post-LT progressive fibrosis (stage > or =2), the 2 post-LT hepatitis categories were regrouped as progressive (n = 24) and nonprogressive (n = 37). High viral counts, HCV genotype 1, and native liver inflammation grade 2 or higher with plasmacytic periseptitis were more frequent in progressive cases than nonprogressive or nonrecurrent cases. Sex mismatch of male recipient and female donor was more common in nonrecurrent group. Overall, death rate was comparable in all groups; however, post-LT HCV-related deaths were more common in progressive cases. In conclusion (1) two thirds (66.2%) of HCV patients developed histologic hepatitis after LT with either typical or AIH-like features; (2) progressive fibrosis was seen in 39.3% of patients with post-LT hepatitis and 26% of the entire study group and was more frequent in AIH-like cases; (3) inflammation grade 2 or higher with plasmacytic periseptitis in native livers may be a predictor of post-LT progressive fibrosis; and (4) male recipient/female donor combination was more common in nonrecurrent cases.

Cyclooxygenase-2 expression in hepatocellular carcinoma, cirrhosis and chronic hepatitis in the United States.

UNLABELLED: Aberrant expression of cyclooxygenase-2 in hepatocellular carcinoma was described in Asia. Using immunohistochemistry, we studied the expression of cyclooxygenase-2 in hepatocellular carcinoma, chronic hepatitis, and cirrhosis in a US institution. A staining score of 0-5 representing the sum of an intensity score and a distribution score was used. The mean scores were 2.2+/-1.60 for chronic hepatitis, 4.37+/-1.15 for cirrhosis, and 4.76+/-0.54 for hepatocellular carcinoma. We found a significant difference in mean staining scores between chronic hepatitis and cirrhosis (p < 0.0001), as well as between chronic hepatitis and hepatocellular carcinoma (p < 0.0001). Fibrosis correlated with cyclooxygenase-2 staining score (r=0.65). IN CONCLUSION: (1) Cyclooxygenase-2 expression is higher in cirrhosis and hepatocellular carcinoma when compared to chronic hepatitis. (2) Cyclooxygenase-2 expression correlates with the stage of fibrosis. (3) These results imply that in chronic hepatitis and possibly in cirrhosis, hepatocarcinogenesis may be a cyclooxygenase-2 dependent mechanism.

Liver biopsy interpretation for causes of late liver allograft dysfunction.

Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.

Impact of model for end-stage liver disease (MELD) scoring system on pathological findings at and after liver transplantation.

The Model for End-Stage Liver Disease (MELD) scoring system, a validated objective liver disease severity scale, was adopted in February 2002 to allocate cadaveric organs for liver transplantation (LT). To improve transplantability before succumbing to advanced disease, patients with low-stage hepatocellular carcinoma (HCC) are given extra points in this system commensurate with their predicted mortality. Our aims were to determine 1) any change in the pathological findings at LT following the implementation of this system and 2) the impact of scoring advantage given to early-stage HCC. Clinicopathologic findings were compared before (pre-MELD, n = 87) and after (MELD, n = 58) the introduction of the MELD system. The findings in the pre-MELD vs. MELD groups were as follows: HCC, 27.5% vs. 48.3% (P = 0.001); portal vein thrombosis (PVT), 13.7% vs. 25.9% (P = 0.08); cholestasis, 16.1% vs. 32.7% (P = 0.026); inflammation grade of 2 or more, 43.7% vs. 48.3% (P = not significant); hepatitis C (HCV), 45.9% vs. 51.7% (P = not significant); HCV with lymphoid aggregates, 25% vs. 60% (P = 0.003); HCV with hyperplastic hilar nodes, 15.0% vs. 36.6% (P = 0.001); and post-LT HCC recurrence, 4.1% vs. 3.4% (P = not significant). Non-HCC-related findings were further compared in the 2 subgroups of pre-MELD (n = 57) and MELD (n = 31) after exclusion of HCC and fulminant hepatic failure (FHF) cases, and only cholestasis was significantly increased in the subgroup MELD. In conclusion, increased incidence of native liver cholestasis in the MELD era may be the histologic correlate of clinically severe liver disease. The scoring advantage given to low-stage HCC did result in a significantly increased incidence of HCC in the MELD group, but it did not adversely affect the post-LT recurrence rate.

Post-liver transplantation de novo hepatitis with overlap features.

The development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults. Reported herein is a case that is best characterized as post-LT de novo hepatitis with features of autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap. A 56-year-old man underwent LT for decompensated liver disease secondary to non-alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 months after LT. Sequential liver transplant biopsy findings were confusing and shared findings seen with both AIH and PBC. Although standard autoimmune serological tests were negative, a dramatic biochemical response was observed to a regimen consisting of prednisone, mycophenolate mofetil, and ursodeoxycholic acid added to maintainance tacrolimus. The donor was histocompatibility leukocyte antigen, DR4, positive, a haplotype associated with the development of AIH-PBC overlap syndrome. In conclusion the authors believe that this may be a case of post-LT de novo overlap syndrome of AIH-PBC, a novel 'autoimmune-type' response.

Excellent outcome following transplantation of a domino donor liver with high-grade macrosteatosis.

Severe macrosteatosis in the donor liver is considered a major predictive factor of primary graft non-function. Such livers are usually discarded despite an ever-growing need for donor livers. We report our recent experience in a patient (#1) who had an excellent outcome following liver transplantation (LT) of a 65-70% macrosteatotic graft and compare his findings with those of two other (#2 and #3) recipients of moderate to severe macrosteatotic grafts. Both patients (#2 and #3) had initial diminished function, with recovery in patient #2 but delayed graft non-function requiring re-LT (day 24) in patient #3. Patient #1 had no intra-operative complications, while patient #2 had mild complications due to prior adhesions and graft capsular laceration. In patient #3, extensive intra-abdominal adhesions resulting in excessive bleeding occurred during recipient hepatectomy. Total ischemic times: 2.48, 6.10, and 8.18 h; total blood product usage: 43, 81, and 223 units; post-LT hospital stay: 9, 21, and 69 days were seen in patients #1, #2 and #3, respectively. In conclusion, post-LT excellent graft function was seen in one recipient of 65-70% macrosteatotic graft. Transplantation of grafts with moderate/severe macrosteatosis may be inadvisable in patients with extensive intra-abdominal adhesions with expectant excessive bleeding and long ischemia times.

Severe steatosis as the initial histologic manifestation of recurrent hepatitis C genotype 3.

Steatosis is a common finding that is seen in patients with both chronic hepatitis C and alcoholic liver disease; however, the extent of involvement in the former is generally minimal to mild. We present 2 patients who underwent live donor liver transplantation for end-stage liver disease that was caused by chronic hepatitis C (genotype 3) and alcohol abuse. Both patients presented with liver allograft dysfunction, with liver biopsy findings of moderate to marked steatosis. Exclusion of a relapse of alcohol use required intense questioning of both the patients and their families. A definitive diagnosis of recurrent hepatitis C was established by viral markers with institution of the proper therapy and resolution of graft dysfunction. We conclude that recurrent hepatitis C, particularly genotype 3, may present with severe steatosis. Recognition of this phenomenon is important, and confirmation with viral markers is necessary to provide optimal patient care.

Native liver xanthogranulomatous cholangiopathy in primary sclerosing cholangitis: impact on posttransplant outcome.

A retrospective analysis of 51 primary sclerosing cholangitis (PSC) patients who underwent liver transplant (LT) identified 16 with xanthogranulomatous cholangiopathy (XGC) at the native liver hilum. Pre-LT clinical and laboratory data and post-LT course and outcome of patients with XGC were compared with the 35 PSC patients without XGC. The XGC and non-XGC groups were similar with respect to age and laboratory data at the time of LT. Pre-LT cholecystectomy was performed in 44% versus 26% and biliary bypass procedure in 38% versus 26% of patients with and without XGC, respectively (P = NS). Peri-operative complications resulted in six (38%) deaths or retransplantation within 60 days of LT in the XGC group compared with 4 (11%) in the non-XGC group (P =.05). Patient survival at 60 and 100 days post-LT was better in the non-XGC group (P =.01). The causes of death or retransplantation within 60 days post-LT in the patients with XGC included primary nongraft function (1), uncontrolled bleeding (3), and sepsis (2), while in the non-XGC group these were uncontrolled bleeding (2), sepsis (1), and primary nongraft function (1). Mean graft survival +/- SD was 1,081 +/- 1,584 days in patients with XGC versus 2,149 +/- 1,679 days in patients without XGC. The presence of XGC in the native liver hilum of PSC patients undergoing LT was associated with a higher rate of early post-LT mortality or retransplantation. In conclusion, no pre-LT clinical features or laboratory tests were identified that predicted the presence of XGC in PSC patients.

Liver transplantation for primary sclerosing cholangitis: a long-term clinicopathologic study.

The course and outcome of patients after liver transplantation (LT) for primary sclerosing cholangitis (PSC) are still debated. Our purpose is to define retrospectively, the post-LT clinicopathologic findings seen in 51 PSC patients with a follow-up of 2 to 14 years. Of the total 51 patients, 16 with native liver hilar xanthogranulomatous cholangiopathy (XGC) had median graft and patient survival of 573 and 835 days, respectively compared with 2489 and 2794 days, respectively, in 35 patients without XGC. Perioperative complications resulted in 9 early deaths (day 0 to 52). Of the remaining 42 patients, 6 had recurrent PSC (R-PSC) with typical histologic and cholangiographic findings, 12 had autoimmune liver disease-not otherwise specified with histology of autoimmune hepatitis/overlap syndrome, 3 had chronic rejection, 4 had ischemic cholangiopathy, and 17 had no recurrence. The presence of inflammatory bowel disease, total ischemia time of > or =11 hours, recipient-donor ABO and HLA Class I and II matches, and the type of immunosuppression did not affect the post-LT outcome. Recipient-donor gender mismatch was more common in R-PSC than in the nonrecurrent group (P=0.045). Post-LT malignancies were significantly more common in the nonrecurrent cases compared with all others combined (P=0.031) and caused deaths in 4. The majority of deaths (11/13) in other groups were due to sepsis complicating graft dysfunction. In conclusion, allograft autoimmune liver disease was seen in 18 (43%) of 42 long-term post-LT PSC patients, with progression in 5 of 18 patients. Features of PSC were seen in 6 (33%) of 18. Native liver XGC negatively impacted post-LT graft and patient survival. Increased incidence of malignancies in the nonrecurrent group may reflect overimmunosuppression in those patients.

Pathologic analysis of right-lobe graft failure in adult-to-adult live donor liver transplantation.

Live donor adult liver transplantation (LDALT) utilizing right-lobe grafts is now acceptable as an alternative to cadaveric orthotopic liver transplantation (OLT). However, some LDALTs fail and require urgent OLT or result in recipient death. Our aim was to determine the basis of LDALT failure. Liver specimens from 49 LDALT recipients were evaluated and the findings correlated with clinical outcome. Ten patients (20.4%) had either early (< or = 1 month) or late (> 1 month) graft failure. Eight early failures, 7 of which occurred among our first 25 cases, were due to extensive liver parenchymal necrosis as a result of hepatic artery thrombosis (n=3), portal vein thrombosis (n=1), hyperperfusion syndrome (n=1), complete graft thrombosis (n=1) with Factor V Leiden on a regimen of therapeutic heparin (n=1), sepsis and concomitant graft dysfunction with venous outflow tract injury (n=1), and venous outflow tract thrombosis and parenchymal thermal injury with sepsis (n=1). Preoperative, intraoperative, or postoperative severe vessel wall injury was evident in 6/8 early failures. Two patients had late graft failure, 1 from recurrent hepatitis C and 1 with sepsis/multisystem organ failure. There were no significant differences in graft size, rejection episodes, or operative or ischemic times between patients with and without graft failure. In conclusion, LDALT failed in 10/49 (20%) of our patients, with 8/10 occurring within 1 month post-LDALT owing to vascular/thrombotic complications experienced during the early phase of our institutional experience. Perioperative vessel wall injury appeared to be a major factor in predicting early graft loss.

Nodular pulmonary amyloidosis following liver transplantation: report of a case and review of the literature.

Nodular pulmonary lesions seen in liver transplant recipients have a broad differential diagnosis including both infectious and noninfectious etiologies. Here, we report the first case of nodular pulmonary amyloidosis, an uncommon and benign localized form of amyloidosis occurring after orthotopic liver transplantation for end-stage primary biliary cirrhosis.

Invasive pulmonary aspergillosis soon after therapy with infliximab, a tumor necrosis factor-alpha-neutralizing antibody: a possible healthcare-associated case?

BACKGROUND: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor (TNF)-alpha, used for the treatment of Crohn's disease and rheumatoid arthritis. Recently, an increased risk of infection due to Mycobacterium tuberculosis and rare cases of invasive fungal disease have been reported following infliximab therapy. CASE REPORT: A 73-year-old woman with chronic rheumatoid arthritis who had been treated with methotrexate, leflunomide, and prednisone was given the first of three doses of infliximab in June 2001. In July 2001, she presented with cough, and in August, she had a right upper lobe infiltrate that was treated with levofloxacin without improvement. In October, the patient had right upper and middle lobe infiltrates on a chest X-ray and computed tomography scan. At bronchoscopy, an endobronchial mass was biopsied, which demonstrated Aspergills fumigatus. Our patient had frequently accompanied her daughter on visits to another medical center following a stem cell transplant, where her daughter was instructed to wear a mask during all visits because of extensive building construction. We postulate that our patient may have acquired pulmonary aspergillosis during this period. Literature reviews on granulomatous diseases following infliximab therapy and hospital-acquired aspergillosis are presented. CONCLUSION: The temporal relationship between the administration of infliximab and A. fumigatus infection in this patient suggests a causal relationship and possible healthcare-associated acquisition. These data underscore the importance of both patient and family education on prevention strategies when potent immune-modulating medications such as infliximab have been prescribed.

Xanthogranulomatous choledochitis: a previously undescribed mass lesion of the hepatobiliary and ampullary region.

Solid liver and pancreatic masses are commonly neoplastic in nature; however, inflammatory lesions mimicking carcinoma are at times encountered in these sites. We report two cases of previously undescribed inflammatory mass lesions of the liver and pancreas that originated in the biliary tract. Detailed clinical and histologic evaluations were performed in two patients who underwent right partial hepatic lobectomy and Whipple's resection for presumed hepatic and pancreatic neoplasms. In case 1, with a remote history of cholecystectomy and recent extraction of a stone from the common bile duct, a liver mass in segment 6 was discovered incidentally. In case 2, a periampullary pancreatic mass was diagnosed radiographically following papillotomy and stent insertion for stricture and biliary calculous disease. The histologic findings in both cases were similar, localized around a part of the biliary tract, and consisted of inspissated bile, acute and chronic inflammation, abundant lipid-laden macrophages, fibrosis, and giant cell reaction. No neoplasm was identified. On the basis of the close resemblance of these features to those seen in xanthogranulomatous cholecystitis, the lesions seen here were termed xanthogranulomatous choledochitis. In conclusion, xanthogranulomatous choledochitis is a benign inflammatory process involving the biliary tract that can form a mass lesion within the liver or pancreas and thus mimic a neoplasm. Extensive sampling of the lesion is required to rule out an underlying neoplastic process. In our patients a propensity to form lithogenic bile and a prior history of biliary tract operative procedure were present.

Fine-needle aspiration biopsy of a cystic pleomorphic adenoma with extensive adnexa-like differentiation: differential diagnostic pitfall with mucoepidermoid carcinoma.

Although fine-needle aspiration biopsy (FNAB) is a highly accurate tool for the diagnosis of pleomorphic adenomas, even this common salivary gland neoplasm can be diagnostically challenging and cause pitfalls in cytodiagnosis. In particular, the presence of either cystic degeneration or squamous and mucinous metaplasia can lead to a false positive diagnosis of malignancy. Here we present the case of a 16-year-old female who presented with a painless, slowly growing mass in the superficial lobe of the right parotid gland. Magnetic resonance imaging of the parotid demonstrated a mass with heterogeneous postcontrast enhancement and a central, nonenhancing area suggestive of necrosis. FNAB of the lesion yielded proteinaceous debris and numerous whorls of keratin, small cohesive clusters of basaloid and squamoid epithelial cells, and many vacuolated and foamy cells. Initially and after consultation at an outside institution, the FNAB was reported as an "atypical neoplasm, cannot exclude mucoepidermoid carcinoma." A total, nerve-sparing parotidectomy and level II neck dissection revealed a pleomorphic adenoma with central cystic degeneration and extensive mixed appendageal differentiation. While foci of squamous metaplastic changes may occur in pleomorphic adenomas, the combination of cystic degeneration and extensive appendageal differentiation with numerous keratotic cysts is rare, and it presents the potential for misinterpretation of the FNAB as indicative of malignancy in general, and mucoepidermoid carcinoma in particular.