Composite diffuse large B-cell lymphomas (DLBCLs) with peripheral T-cell lymphomas (PTCLs) are ra... more Composite diffuse large B-cell lymphomas (DLBCLs) with peripheral T-cell lymphomas (PTCLs) are rare co-occurrences with poorly understood pathologic features. Herein, we describe 15 distinct cases of DLBCL occurring in association with PTCL, including angioimmunoblastic T-cell lymphoma (AITL; n = 12) and PTCL, not otherwise specified (n = 3). Sheets of large B cells were seen in all cases, with Hodgkin/Reed-Sternberg-like (HRS-L) cells present in 6 cases. When compared to cases of AITL without DLBCL, HRS-L cells were more frequently seen in cases of AITL with DLBCL (P = .02). Epstein-Barr virus (EBV) expression was seen in 10 of 15 cases, and in those with HRS-L cells, EBV expression was detected invariably in at least a subset of the HRS-L cells. MYC gene rearrangements were consistently absent, although 6 of the 10 cases showed MYC overexpression by immunohistochemistry in the neoplastic B cells; a frequency significantly increased compared to other cases of DLBCL not associated with a T-cell lymphoma: 29 of 166 (P = .005). In addition, when MYC was overexpressed in DLBCL, it was also weakly present in the HRS-L cells. The increased and frequent morphologic presence of HRS-L cells in association with this composite lymphoma raises a possible link between their occurrence and DLBCLs in PTCLs; furthermore, the frequent detection of MYC protein expression and EBV infection in these cases suggests a possible role of these pathways in B-cell lymphomagenesis.
Proceedings of The National Academy of Sciences, 2009
The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80... more The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon
Primary mediastinal large B-cell lymphoma (PMLBL) is an aggressive B-cell lymphoma typically loca... more Primary mediastinal large B-cell lymphoma (PMLBL) is an aggressive B-cell lymphoma typically localized to the mediastinum. To date, no study has undertaken a comprehensive analysis of this entity by multiparameter flow cytometry. Cases of PMLBL with diagnostic flow cytometry were identified from pathology databases of Boston Children's Hospital, Brigham and Women's Hospital, and Stanford Hospital. Most of these patients with PMLBL were women with a median age of 30 years who had stage 1 disease that lacked bone marrow involvement. By flow cytometry, 50% of all PMLBLs showed restricted surface immunoglobulin expression. When comparing patients with PMLBL by the absence or presence of surface light chain immunoglobulins, no differences were seen in the morphologic appearance; expression of CD23, CD30, or CD10; age at presentation; or clinical stage (P > .5 for all). In addition, both groups showed similarly good survival outcomes and were alive at last follow-up (11/14 [79%...
T his article focuses on the challenges of generating comprehensive diagnostic reports in hematop... more T his article focuses on the challenges of generating comprehensive diagnostic reports in hematopathology. In particular, two main challenges that diagnosticians face are (1) interpreting and understanding the rapid advances in molecular and genetic pathology, which have gained increasing importance in classifications of hematopoietic neoplasms, and (2) managing the logistics of reporting ancillary studies and incorporating them effectively into a final synthesized report. This article summarizes many important genetic findings in hematopoietic neoplasms, which are required for accurate diagnoses, and discusses practical issues to generating accurate and complete hematopathology reports.
B-lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) is... more B-lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) is a relatively uncommon manifestation of acute leukemia and limited predominantly to the pediatric population. Case-specific information regarding flow cytometric, morphologic, and laboratory findings of this subtype of leukemia is currently lacking. We searched the databases of three large institutions for lymphoblastic leukemia with iAMP21 from 2005 through 2012 and analyzed the clinicopathologic features. We identified 17 cases with five or more RUNX1 signals on interphase nuclei, 14 of which were consistent with the Children's Oncology Group (COG) definition for iAMP21-namely, the presence of three or more RUNX1 signals on one marker chromosome. These cases showed a statistically significant lower peripheral WBC count and older age at diagnosis compared with all pediatric cases of B-ALL. We also identified three cases with increased RUNX1 signals scattered on multiple marker chrom...
We sought to determine the significance of bright CD45 expression on mast cells in cases of syste... more We sought to determine the significance of bright CD45 expression on mast cells in cases of systemic mastocytosis vs mast cells in bone marrows uninvolved by systemic mastocytosis and compare this CD45 expression with CD25 and CD2 expression on mast cells. Multiparameter flow cytometry was performed on 31 cases of systemic mastocytosis and 70 bone marrow cases that were not involved by systemic mastocytosis. Bright expression of CD45 was defined as more than 20% of CD117+ mast cells showing brighter CD45 expression than the average expression level of lymphocytes. Mast cells with bright CD45 expression were seen in 26 systemic mastocytosis cases and three bone marrows uninvolved by systemic mastocytosis (sensitivity, 84%; specificity, 96%). CD25 alone had a greater sensitivity (100%) but lower specificity (93%) compared with bright CD45 for identifying abnormal mast cells, while CD2 alone had lower sensitivity but higher specificity. To reach a specificity of 100%, CD25 together wit...
To characterize the clinicopathologic features of cases of large B-cell lymphomas, poor in B cell... more To characterize the clinicopathologic features of cases of large B-cell lymphomas, poor in B cells and densely rich in programmed cell death-1 (PD-1)+ reactive T cells, which can mimic T-cell lymphomas. A single-institute retrospective review of cases between 2010 and 2013 was performed. Of 178 cases of large B-cell lymphomas, eight cases of large B-cell lymphomas poor in B cells and diffusely rich in sheets of PD-1+ T cells were identified. These cases either were initially misdiagnosed as a T-cell lymphoma or substantiated a broader differential diagnosis including a T-cell lymphoma. Five cases were T-cell histiocyte-rich large B-cell lymphomas, and three cases were diagnosed as large B-cell lymphomas rich in T cells. In three of these cases, a subset of the PD-1+ T cells showed either morphologic nuclear atypia or atypical expression of T-cell antigens on flow cytometry and/or immunohistochemistry. Large B-cell lymphomas poor in B cells and rich in T cells can have diffuse sheets...
We assessed the frequency and clinicopathologic significance of 19 genes currently identified as ... more We assessed the frequency and clinicopathologic significance of 19 genes currently identified as significantly mutated in myeloid neoplasms, RUNX1, ASXL1, TET2, CEBPA, IDH1, IDH2, DNMT3A, FLT3, NPM1, TP53, NRAS, EZH2, CBL, U2AF1, SF3B1, SRSF2, JAK2, CSF3R, and SETBP1, across 93 cases of acute myeloid leukemia (AML) using capture target enrichment and next-generation sequencing. Of these cases, 79% showed at least one nonsynonymous mutation, and cases of AML with recurrent genetic abnormalities showed a lower frequency of mutations versus AML with myelodysplasia-related changes (P<0.001). Mutational analysis further demonstrated that TP53 mutations are associated with complex karyotype AML, whereas ASXL1 and U2AF1 mutations are associated with AML with myelodysplasia-related changes. Furthermore, U2AF1 mutations were specifically associated with trilineage morphologic dysplasia. Univariate analysis demonstrated that U2AF1 and TP53 mutations are associated with absence of clinical remission, poor overall survival (OS), and poor disease-free survival (DFS; P<0.0001), whereas TET2 and ASXL1 mutations are associated with poor OS (P<0.03). In multivariate analysis, U2AF1 and TP53 mutations retained independent prognostic significance in OS and DFS, respectively. Our results demonstrate unique relationships between mutations in AML, clinicopathologic prognosis, subtype categorization, and morphologic dysplasia.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.160.
Acute myeloid leukemia (AML) with monosomal karyotype (MK) recently has been reported to be assoc... more Acute myeloid leukemia (AML) with monosomal karyotype (MK) recently has been reported to be associated with worse outcome than the traditional complex karyotype. In this retrospective study of 111 patients with AML, we identified 14 patients with MK (13% of all patients with AML) using the definition proposed by Breems et al. Five (36%) of these 14 patients had a loss of a single chromosome in the presence of other structural abnormalities, and nine (64%) had a loss of two or more autosomal chromosomes. Patients with AML-MK presented at an older age, with lower bone marrow blasts, and their blasts less frequently expressed CD34. Most patients with AML-MK had morphologic multilineage dysplasia and were predominantly subclassified as having AML with myelodysplasia-related changes (AML-MRC). Molecular analysis showed a significant absence of NPM1 and FLT3 in patients with AML-MK. Outcome data showed that patients with AML-MK had significantly worse overall survival, disease-free surviv...
Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular ly... more Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular lymphoma arising in adults. Here, we describe a rare case of pFL that showed morphologic features partially overlapping with progressive transformation of germinal centers and reactive follicular hyperplasia. As typical of pFL, neoplastic B cells within follicles did not express B-cell leukemia/lymphoma 2 (BCL2). However, this case showed additional distinctive abnormal findings, which contributed to the diagnosis: (1) diffuse and uniform staining of immunoglobulin M (IgM) on cells within and outside of follicles, (2) abnormally dim expression of CD21 on follicular dendritic cells, and (3) expression of human germinal center-associated lymphoma (HGAL) and LIM domain only 2 (LMO2) on B cells in interfollicular and follicular areas. This case demonstrates the utility of these abnormal features, which can be seen in adult- or usual-type follicular lymphoma, in the diagnosis of pFL. Further studies are necessary to evaluate the significance of these findings in other cases of pFL.
Proceedings of the National Academy of Sciences, 2008
This dissertation has been read by each member of the dissertation committee and has been found t... more This dissertation has been read by each member of the dissertation committee and has been found to be satisfactory regarding content, English usage, format, citation, bibliographic style, and consistency, and is ready for submission to the Division of Graduate Education.
PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a ... more PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a variety of organs. Very little is known about the role of PAX8 in endocrine cell development and the expression of PAX8 in neuroendocrine tumors. The purpose of this study was to analyze PAX8 immunohistochemical expression in gastroenteropancreatic and pulmonary well-differentiated neuroendocrine tumors to determine whether PAX8 can reliably distinguish pancreatic neuroendocrine tumors from neuroendocrine tumors of other anatomic sites and other pancreatic non-ductal neoplasms. In total, 221 well-differentiated neuroendocrine tumors were evaluated: 174 primary neuroendocrine tumors (66 pancreatic, 31 ileal, 21 pulmonary, 20 gastric, 17 rectal, 11 appendiceal, and 8 duodenal) and 47 neuroendocrine tumors metastatic to the liver (31 pancreatic, 11 ileal, 2 pulmonary, 2 duodenal, and 1 rectal). Fifteen solid-pseudopapillary neoplasms and six acinar cell carcinomas of the pancreas were also evaluated. PAX8 was positive in 49/66 (74%) primary pancreatic neuroendocrine tumors. PAX8 expression did not correlate with World Health Organization categorization, grade, size, functional status, or the presence of liver or lymph node metastasis. PAX8 expression was identified in 0/31 (0%) ileal, 0/21 (0%) pulmonary, 2/20 (10%) gastric, 5/17 (29%) rectal, 1/11 (9%) appendiceal, and 6/8 (75%) duodenal neuroendocrine tumors. PAX8 was positive in 4/15 (27%) solid-pseudopapillary neoplasms of the pancreas, whereas all acinar cell carcinomas (0/6) lacked immunoreactivity. Among liver metastases, only pancreatic neuroendocrine tumors (20/31, 65%) were PAX8 positive, whereas no cases of ileal (0/11), pulmonary (0/2), duodenal (0/2), and rectal (0/1) neuroendocrine tumor metastases were PAX8 positive. PAX8 is expressed in primary and metastatic pancreatic well-differentiated neuroendocrine tumors, and its expression can reliably distinguish pancreatic from ileal and pulmonary well-differentiated neuroendocrine tumors. Duodenal neuroendocrine tumors and a subset of rectal, gastric, and appendiceal neuroendocrine tumors may also express PAX8. PAX8 expression can distinguish pancreatic neuroendocrine tumors from acinar cell carcinomas, but its utility in distinguishing neuroendocrine tumors from solid-pseudopapillary neoplasms is limited.
Composite diffuse large B-cell lymphomas (DLBCLs) with peripheral T-cell lymphomas (PTCLs) are ra... more Composite diffuse large B-cell lymphomas (DLBCLs) with peripheral T-cell lymphomas (PTCLs) are rare co-occurrences with poorly understood pathologic features. Herein, we describe 15 distinct cases of DLBCL occurring in association with PTCL, including angioimmunoblastic T-cell lymphoma (AITL; n = 12) and PTCL, not otherwise specified (n = 3). Sheets of large B cells were seen in all cases, with Hodgkin/Reed-Sternberg-like (HRS-L) cells present in 6 cases. When compared to cases of AITL without DLBCL, HRS-L cells were more frequently seen in cases of AITL with DLBCL (P = .02). Epstein-Barr virus (EBV) expression was seen in 10 of 15 cases, and in those with HRS-L cells, EBV expression was detected invariably in at least a subset of the HRS-L cells. MYC gene rearrangements were consistently absent, although 6 of the 10 cases showed MYC overexpression by immunohistochemistry in the neoplastic B cells; a frequency significantly increased compared to other cases of DLBCL not associated with a T-cell lymphoma: 29 of 166 (P = .005). In addition, when MYC was overexpressed in DLBCL, it was also weakly present in the HRS-L cells. The increased and frequent morphologic presence of HRS-L cells in association with this composite lymphoma raises a possible link between their occurrence and DLBCLs in PTCLs; furthermore, the frequent detection of MYC protein expression and EBV infection in these cases suggests a possible role of these pathways in B-cell lymphomagenesis.
Proceedings of The National Academy of Sciences, 2009
The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80... more The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon
Primary mediastinal large B-cell lymphoma (PMLBL) is an aggressive B-cell lymphoma typically loca... more Primary mediastinal large B-cell lymphoma (PMLBL) is an aggressive B-cell lymphoma typically localized to the mediastinum. To date, no study has undertaken a comprehensive analysis of this entity by multiparameter flow cytometry. Cases of PMLBL with diagnostic flow cytometry were identified from pathology databases of Boston Children's Hospital, Brigham and Women's Hospital, and Stanford Hospital. Most of these patients with PMLBL were women with a median age of 30 years who had stage 1 disease that lacked bone marrow involvement. By flow cytometry, 50% of all PMLBLs showed restricted surface immunoglobulin expression. When comparing patients with PMLBL by the absence or presence of surface light chain immunoglobulins, no differences were seen in the morphologic appearance; expression of CD23, CD30, or CD10; age at presentation; or clinical stage (P > .5 for all). In addition, both groups showed similarly good survival outcomes and were alive at last follow-up (11/14 [79%...
T his article focuses on the challenges of generating comprehensive diagnostic reports in hematop... more T his article focuses on the challenges of generating comprehensive diagnostic reports in hematopathology. In particular, two main challenges that diagnosticians face are (1) interpreting and understanding the rapid advances in molecular and genetic pathology, which have gained increasing importance in classifications of hematopoietic neoplasms, and (2) managing the logistics of reporting ancillary studies and incorporating them effectively into a final synthesized report. This article summarizes many important genetic findings in hematopoietic neoplasms, which are required for accurate diagnoses, and discusses practical issues to generating accurate and complete hematopathology reports.
B-lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) is... more B-lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) is a relatively uncommon manifestation of acute leukemia and limited predominantly to the pediatric population. Case-specific information regarding flow cytometric, morphologic, and laboratory findings of this subtype of leukemia is currently lacking. We searched the databases of three large institutions for lymphoblastic leukemia with iAMP21 from 2005 through 2012 and analyzed the clinicopathologic features. We identified 17 cases with five or more RUNX1 signals on interphase nuclei, 14 of which were consistent with the Children's Oncology Group (COG) definition for iAMP21-namely, the presence of three or more RUNX1 signals on one marker chromosome. These cases showed a statistically significant lower peripheral WBC count and older age at diagnosis compared with all pediatric cases of B-ALL. We also identified three cases with increased RUNX1 signals scattered on multiple marker chrom...
We sought to determine the significance of bright CD45 expression on mast cells in cases of syste... more We sought to determine the significance of bright CD45 expression on mast cells in cases of systemic mastocytosis vs mast cells in bone marrows uninvolved by systemic mastocytosis and compare this CD45 expression with CD25 and CD2 expression on mast cells. Multiparameter flow cytometry was performed on 31 cases of systemic mastocytosis and 70 bone marrow cases that were not involved by systemic mastocytosis. Bright expression of CD45 was defined as more than 20% of CD117+ mast cells showing brighter CD45 expression than the average expression level of lymphocytes. Mast cells with bright CD45 expression were seen in 26 systemic mastocytosis cases and three bone marrows uninvolved by systemic mastocytosis (sensitivity, 84%; specificity, 96%). CD25 alone had a greater sensitivity (100%) but lower specificity (93%) compared with bright CD45 for identifying abnormal mast cells, while CD2 alone had lower sensitivity but higher specificity. To reach a specificity of 100%, CD25 together wit...
To characterize the clinicopathologic features of cases of large B-cell lymphomas, poor in B cell... more To characterize the clinicopathologic features of cases of large B-cell lymphomas, poor in B cells and densely rich in programmed cell death-1 (PD-1)+ reactive T cells, which can mimic T-cell lymphomas. A single-institute retrospective review of cases between 2010 and 2013 was performed. Of 178 cases of large B-cell lymphomas, eight cases of large B-cell lymphomas poor in B cells and diffusely rich in sheets of PD-1+ T cells were identified. These cases either were initially misdiagnosed as a T-cell lymphoma or substantiated a broader differential diagnosis including a T-cell lymphoma. Five cases were T-cell histiocyte-rich large B-cell lymphomas, and three cases were diagnosed as large B-cell lymphomas rich in T cells. In three of these cases, a subset of the PD-1+ T cells showed either morphologic nuclear atypia or atypical expression of T-cell antigens on flow cytometry and/or immunohistochemistry. Large B-cell lymphomas poor in B cells and rich in T cells can have diffuse sheets...
We assessed the frequency and clinicopathologic significance of 19 genes currently identified as ... more We assessed the frequency and clinicopathologic significance of 19 genes currently identified as significantly mutated in myeloid neoplasms, RUNX1, ASXL1, TET2, CEBPA, IDH1, IDH2, DNMT3A, FLT3, NPM1, TP53, NRAS, EZH2, CBL, U2AF1, SF3B1, SRSF2, JAK2, CSF3R, and SETBP1, across 93 cases of acute myeloid leukemia (AML) using capture target enrichment and next-generation sequencing. Of these cases, 79% showed at least one nonsynonymous mutation, and cases of AML with recurrent genetic abnormalities showed a lower frequency of mutations versus AML with myelodysplasia-related changes (P<0.001). Mutational analysis further demonstrated that TP53 mutations are associated with complex karyotype AML, whereas ASXL1 and U2AF1 mutations are associated with AML with myelodysplasia-related changes. Furthermore, U2AF1 mutations were specifically associated with trilineage morphologic dysplasia. Univariate analysis demonstrated that U2AF1 and TP53 mutations are associated with absence of clinical remission, poor overall survival (OS), and poor disease-free survival (DFS; P<0.0001), whereas TET2 and ASXL1 mutations are associated with poor OS (P<0.03). In multivariate analysis, U2AF1 and TP53 mutations retained independent prognostic significance in OS and DFS, respectively. Our results demonstrate unique relationships between mutations in AML, clinicopathologic prognosis, subtype categorization, and morphologic dysplasia.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.160.
Acute myeloid leukemia (AML) with monosomal karyotype (MK) recently has been reported to be assoc... more Acute myeloid leukemia (AML) with monosomal karyotype (MK) recently has been reported to be associated with worse outcome than the traditional complex karyotype. In this retrospective study of 111 patients with AML, we identified 14 patients with MK (13% of all patients with AML) using the definition proposed by Breems et al. Five (36%) of these 14 patients had a loss of a single chromosome in the presence of other structural abnormalities, and nine (64%) had a loss of two or more autosomal chromosomes. Patients with AML-MK presented at an older age, with lower bone marrow blasts, and their blasts less frequently expressed CD34. Most patients with AML-MK had morphologic multilineage dysplasia and were predominantly subclassified as having AML with myelodysplasia-related changes (AML-MRC). Molecular analysis showed a significant absence of NPM1 and FLT3 in patients with AML-MK. Outcome data showed that patients with AML-MK had significantly worse overall survival, disease-free surviv...
Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular ly... more Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular lymphoma arising in adults. Here, we describe a rare case of pFL that showed morphologic features partially overlapping with progressive transformation of germinal centers and reactive follicular hyperplasia. As typical of pFL, neoplastic B cells within follicles did not express B-cell leukemia/lymphoma 2 (BCL2). However, this case showed additional distinctive abnormal findings, which contributed to the diagnosis: (1) diffuse and uniform staining of immunoglobulin M (IgM) on cells within and outside of follicles, (2) abnormally dim expression of CD21 on follicular dendritic cells, and (3) expression of human germinal center-associated lymphoma (HGAL) and LIM domain only 2 (LMO2) on B cells in interfollicular and follicular areas. This case demonstrates the utility of these abnormal features, which can be seen in adult- or usual-type follicular lymphoma, in the diagnosis of pFL. Further studies are necessary to evaluate the significance of these findings in other cases of pFL.
Proceedings of the National Academy of Sciences, 2008
This dissertation has been read by each member of the dissertation committee and has been found t... more This dissertation has been read by each member of the dissertation committee and has been found to be satisfactory regarding content, English usage, format, citation, bibliographic style, and consistency, and is ready for submission to the Division of Graduate Education.
PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a ... more PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a variety of organs. Very little is known about the role of PAX8 in endocrine cell development and the expression of PAX8 in neuroendocrine tumors. The purpose of this study was to analyze PAX8 immunohistochemical expression in gastroenteropancreatic and pulmonary well-differentiated neuroendocrine tumors to determine whether PAX8 can reliably distinguish pancreatic neuroendocrine tumors from neuroendocrine tumors of other anatomic sites and other pancreatic non-ductal neoplasms. In total, 221 well-differentiated neuroendocrine tumors were evaluated: 174 primary neuroendocrine tumors (66 pancreatic, 31 ileal, 21 pulmonary, 20 gastric, 17 rectal, 11 appendiceal, and 8 duodenal) and 47 neuroendocrine tumors metastatic to the liver (31 pancreatic, 11 ileal, 2 pulmonary, 2 duodenal, and 1 rectal). Fifteen solid-pseudopapillary neoplasms and six acinar cell carcinomas of the pancreas were also evaluated. PAX8 was positive in 49/66 (74%) primary pancreatic neuroendocrine tumors. PAX8 expression did not correlate with World Health Organization categorization, grade, size, functional status, or the presence of liver or lymph node metastasis. PAX8 expression was identified in 0/31 (0%) ileal, 0/21 (0%) pulmonary, 2/20 (10%) gastric, 5/17 (29%) rectal, 1/11 (9%) appendiceal, and 6/8 (75%) duodenal neuroendocrine tumors. PAX8 was positive in 4/15 (27%) solid-pseudopapillary neoplasms of the pancreas, whereas all acinar cell carcinomas (0/6) lacked immunoreactivity. Among liver metastases, only pancreatic neuroendocrine tumors (20/31, 65%) were PAX8 positive, whereas no cases of ileal (0/11), pulmonary (0/2), duodenal (0/2), and rectal (0/1) neuroendocrine tumor metastases were PAX8 positive. PAX8 is expressed in primary and metastatic pancreatic well-differentiated neuroendocrine tumors, and its expression can reliably distinguish pancreatic from ileal and pulmonary well-differentiated neuroendocrine tumors. Duodenal neuroendocrine tumors and a subset of rectal, gastric, and appendiceal neuroendocrine tumors may also express PAX8. PAX8 expression can distinguish pancreatic neuroendocrine tumors from acinar cell carcinomas, but its utility in distinguishing neuroendocrine tumors from solid-pseudopapillary neoplasms is limited.
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