RESUMO
Salivary gland amyloidosis is an uncommon diagnosis. Most studies have focused on minor salivary gland biopsies as a surrogate site for diagnosing systemic amyloidosis, while only few studies have investigated major salivary gland amyloidosis. We retrospectively identified 57 major and minor salivary gland amyloidosis cases typed using a proteomics-based method between 2010 and 2022. Frequency of amyloid types, clinicopathologic features, and distribution patterns of amyloid deposits were assessed. The indication for salivary gland biopsy/resection (known in 34 cases) included suspected amyloidosis (N = 14; 41.2%), lesion/mass (N = 12; 35.3%), swelling/enlargement (N = 5; 14.7%), and rule out Sjogren syndrome (N = 3; 8.8%). Concurrent pathology was reported in 16 cases, and included chronic sialadenitis (N = 11), extranodal marginal zone lymphoma (N = 3), plasma cell neoplasm (N = 1), and pleomorphic adenoma (N = 1). We identified 3 types of amyloidosis: immunoglobulin light chain/AL (N = 47; 82.5%); immunoglobulin heavy chain/AH (N = 1; 1.8%), and transthyretin/ATTR (N = 9; 15.8%). The patterns of amyloid deposits (assessed in 35 cases) included: 1) Perivascular and/or periductal distribution (N = 18; 51.4%); 2) Mass formation (N = 9; 25.7%); 3) Stromal micronodule formation (N = 7; 20.0%); and 4) Diffuse interstitial involvement (N = 1; 2.9%). We also identified one case of AL amyloidosis localized to the major salivary gland, where only 6 other cases with adequate staging workup to exclude systemic amyloidosis were previously reported. In conclusion, salivary gland amyloidosis is an uncommon diagnosis but may be underrecognized due to low index of suspicion. Most cases of salivary gland amyloidosis are AL type, but a minority are ATTR. Therefore, proteomics-based typing remains essential for treatment and prognosis.
Assuntos
Neuropatias Amiloides Familiares , Pré-Albumina , Humanos , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/patologia , Neuropatias Amiloides Familiares/complicações , Amiloidose/patologia , Amiloidose/complicações , Amiloidose/diagnóstico , Amiloidose/genética , Pré-Albumina/genéticaRESUMO
OBJECTIVES: To determine the prevalence of different amyloid types and frequency of associated systemic amyloidosis in the urinary tract/prostate. METHODS: We studied Congo red-positive prostate (n = 150) and urinary tract (n = 767) specimens typed by a proteomics-based method between 2008 and 2020. Clinical follow up was available for a subset (urinary tract, n = 111; prostate, n = 17). Amyloid types were correlated with various clinicopathologic features. For patients with clinical follow up, chart review was performed to establish localized versus systemic disease, frequency of initial diagnosis of amyloidosis on urinary tract/prostate specimens, presence of cardiac disease, and death from disease-related complications. RESULTS: The most common amyloid types were AL/AH in urinary tract (479/767, 62 %) and localized ASem1 in prostate (64/150, 43 %). Urinary tract AL/AH amyloid was usually localized, but systemic AL amyloidosis occurred in both sites (urinary tract: 5/71, 7 %; prostate: 2/2, 100 %). ATTR amyloidosis was seen in over a third of cases (urinary tract: 286/767, 37 %; prostate: 55/150, 37 %). Urinary tract/prostate was the site of the initial ATTR amyloidosis diagnosis in 44/48 patients (92 %), and 38/48 (79 %) were subsequently found to have cardiac involvement. Seminal vesicle/ejaculatory duct involvement was pathognomonic for ASem1-type amyloidosis (39/39, 100 %). CONCLUSIONS: Over 40 % of patients had systemic amyloidosis, with urinary tract/prostate often the first site in which amyloid was identified. Since early recognition of systemic amyloidosis is critical for optimal patient outcomes, there should be a low threshold to perform Congo red stain. Proteomics-based amyloid typing is recommended since treatment depends on correctly identifying the amyloid type.
Assuntos
Amiloidose , Sistema Urinário , Masculino , Humanos , Próstata/patologia , Vermelho Congo , Amiloidose/diagnóstico , Amiloidose/patologia , Amiloide , Sistema Urinário/patologia , Diagnóstico PrecoceRESUMO
The gastrointestinal (GI) tract is a common site of amyloidosis, but the incidence, clinicopathologic features, and systemic implications of different types of GI amyloidosis are not well understood. GI amyloid specimens (N = 2511) typed using a proteomics-based method between 2008 and 2021 were identified. Clinical and morphologic features were reviewed in a subset of cases. Twelve amyloid types were identified, including AL (77.9%), ATTR (11.3%), AA (6.6%), AH (1.1%), AApoAIV (1.1%), AEFEMP1 (0.7%), ALys (0.4%), AApoAI (0.4%), ALECT2 (0.2%), Aß2M (0.1%), AGel (0.1%), and AFib (<0.1%). Amino acid abnormalities indicative of known amyloidogenic mutations were detected in 24.4% ATTR cases. AL, ATTR, and AA types all commonly involved submucosal vessels. They also showed some characteristic patterns of involvement of more superficial anatomic compartments, although there was significant overlap. Common indications for biopsy were diarrhea, GI bleed, abdominal pain, or weight loss. Amyloidosis was usually an unexpected finding, but most AL and ATTR patients were ultimately found to have cardiac involvement (83.5% of AL; 100% of ATTR). Although most GI amyloid is of AL type, over 10% are ATTR, over 5% are AA, and twelve different types were identified in total. GI amyloid is often unexpected but usually signals systemic amyloidosis, thus there should be a low threshold to perform biopsy with Congo red stain in patients with unexplained GI symptoms. Clinical and histologic features are nonspecific, and typing should be performed via a robust method such as proteomics as treatment hinges on correctly identifying the amyloid type.
Assuntos
Amiloidose , Humanos , Amiloidose/genética , Amiloidose/diagnóstico , Amiloide/metabolismo , Trato Gastrointestinal/patologia , Vermelho Congo , BiópsiaRESUMO
OBJECTIVES: There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. METHODS: Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red-stained sections were re-reviewed. RESULTS: Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)-type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma). CONCLUSIONS: This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)-type penile amyloid.
Assuntos
Amiloidose , Pré-Albumina , Masculino , Humanos , Estudos Retrospectivos , Proteômica/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Amiloidose/diagnóstico , Amiloidose/patologia , Amiloide/análise , Pênis/química , Pênis/patologia , QueratinasRESUMO
The spleen is a commonly encountered specimen in surgical pathology. However, little is known about the incidence, morphologic pattern, and clinical features of spleens involved by amyloidosis. We retrospectively identified 69 spleen amyloid cases typed using a proteomics-based method between 2008 and 2020. The frequency of amyloid types, clinicopathologic features, and distribution of amyloid deposits were assessed. Four amyloid types were detected: immunoglobulin light chain (AL) (N=30; 43.5%); leukocyte chemotactic factor 2 amyloidosis (ALECT2) (N=30; 43.5%); amyloid A (AA) (N=8; 11.6%); and fibrinogen alpha (AFib) (N=1; 1.4%). The splenic amyloid showed 5 distinct distribution patterns: (1) diffuse pattern, exhibited by most AL cases; (2) red pulp pattern, exhibited by most ALECT2 cases; (3) multinodular pattern, seen in subsets of AA and AL-kappa cases; (4) mass-forming pattern, seen in the AFib case; and (5) vascular only, seen in a subset of AA cases. Atraumatic splenic rupture was the most common reason for splenectomy in AL cases, while most ALECT2 spleens were removed incidentally during an unrelated abdominal surgery. Splenomegaly was significantly more common in AA spleens than in AL or ALECT2 spleens and was often the reason for splenectomy in this group. In conclusion, splenic amyloid may be underrecognized as it is often an incidental finding. Although, as expected, many of the spleens were involved by AL amyloidosis, ALECT2 emerged as another common spleen amyloid type. Although the spleen amyloid types exhibited characteristic distribution patterns, proteomics-based typing is warranted as some morphologic overlap still exists. Awareness of ALECT2 as a major spleen amyloid type is important for appropriate diagnostic workup and patient management.
Assuntos
Amiloidose , Fibrilação Atrial , Humanos , Proteômica , Baço/cirurgia , Baço/patologia , Estudos Retrospectivos , Amiloidose/patologia , AmiloideRESUMO
BACKGROUND: Bone marrow biopsy is common in patients suspected of having systemic AL amyloidosis. However, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid types in bone marrow. METHODS: We retrospectively identified N = 1469 bone marrow amyloid biopsies typed using a proteomics-based method between 2008-2020. Frequency of amyloid types (N = 1469), distribution of amyloid deposits (N = 139), and clinical phenotypes (N = 355), with particular emphasis on cardiac involvement, were assessed. RESULTS: The amyloid types were: AL (N = 1172; 79.8%), ATTR (N = 240; 16.3%), AH (N = 38; 2.6%), AA (N = 17; 1.2%), and Aß2M (N = 2; 0.1%). Although there were characteristic morphologic features, including periosteal soft tissue and/or vascular involvement in ATTR, interstitial vascular involvement in AA, and variable anatomic compartment involvement in AL, none were pathognomonic. Most patients with both an M-spike and cardiac involvement had AL amyloid in their BM, but in over 10% the amyloid type was ATTR. Compared to AL patients, ATTR patients had higher stage cardiac amyloidosis and lower overall survival, which was mainly due to advanced cardiac stage. CONCLUSIONS: ATTR amyloid is common in bone marrow and its morphologic distribution overlaps with AL. Amyloid typing is critical as over 10% of patients with bone marrow amyloid, cardiac amyloidosis, and an M-spike have ATTR amyloidosis.
Assuntos
Neuropatias Amiloides Familiares , Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Amiloide/análise , Neuropatias Amiloides Familiares/patologia , Proteínas Amiloidogênicas , Amiloidose/patologia , Medula Óssea/patologia , Humanos , Estudos RetrospectivosRESUMO
The distinction between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed-Sternberg cells (CLL-HRS; background milieu with a paucity of inflammatory cells) and overt transformation to classic Hodgkin lymphoma (CLL-HL; mixed inflammatory background) is incompletely understood. This retrospective study examined the clinicopathologic features of CLL-HRS (n = 15) and CLL-HL (n = 31) patients seen over the past three decades from a single institution. The phenotypic features of Reed-Sternberg cells in both groups were similar, including expression of CD30, CD15, and PAX5, as well as EBV status. However, a spectrum of background CLL/SLL infiltration amongst the HRS cells was noted on pathologic review, and four patients had both diagnoses, either concurrently or in succession. The median overall survival (OS) of patients with CLL-HRS was 17.5 months compared to 33.5 months for patients with CLL-HL (P = 0.24). Among patients with CLL-HRS, those who received Hodgkin-directed therapy had a significantly longer median OS (57 months) compared to those who received CLL-directed therapy (8.4 months, P = 0.02). Our clinical and pathologic findings suggest a biologic continuum between CLL-HRS and CLL-HL and indicate that CLL-HRS patients may benefit from Hodgkin-directed therapy.
Assuntos
Doença de Hodgkin/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/patologia , Diagnóstico Diferencial , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
Institutional database search (1999-2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment-induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML.
Assuntos
Segunda Neoplasia Primária/mortalidade , Sarcoma Mieloide/mortalidade , Cariótipo Anormal , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Feminino , Trato Gastrointestinal/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Células Neoplásicas Circulantes , Recidiva , Sarcoma Mieloide/tratamento farmacológico , Sarcoma Mieloide/patologia , Sarcoma Mieloide/terapia , Pele/patologia , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
Proliferative chronic myelomonocytic leukemia (pCMML), an aggressive CMML subtype, is associated with dismal outcomes. RAS pathway mutations, mainly NRASG12D, define the pCMML phenotype as demonstrated by our exome sequencing, progenitor colony assays and a Vav-Cre-NrasG12D mouse model. Further, these mutations promote CMML transformation to acute myeloid leukemia. Using a multiomics platform and biochemical and molecular studies we show that in pCMML RAS pathway mutations are associated with a unique gene expression profile enriched in mitotic kinases such as polo-like kinase 1 (PLK1). PLK1 transcript levels are shown to be regulated by an unmutated lysine methyl-transferase (KMT2A) resulting in increased promoter monomethylation of lysine 4 of histone 3. Pharmacologic inhibition of PLK1 in RAS mutant patient-derived xenografts, demonstrates the utility of personalized biomarker-driven therapeutics in pCMML.
Assuntos
Proteínas de Ciclo Celular/genética , GTP Fosfo-Hidrolases/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia Mielomonocítica Crônica/genética , Proteínas de Membrana/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Animais , Proteínas de Ciclo Celular/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Leucêmica da Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Estimativa de Kaplan-Meier , Leucemia Mielomonocítica Crônica/metabolismo , Leucemia Mielomonocítica Crônica/terapia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/genética , Transplante de Células-Tronco/métodos , Transplante Homólogo , Sequenciamento do Exoma/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Quinase 1 Polo-LikeRESUMO
OBJECTIVES: Pure erythroid leukemia (PEL) is exceptionally rare in the pediatric setting. Four pediatric PEL cases with t(1;16)(p31;q24) NFIA-CBFA2T3 were reported previously. We present a case of an infant with PEL presenting with erythroblastic sarcoma and harboring a novel t(1;8)(p31.3;q21.3) NFIA-RUNX1T1 fusion detected by RNA sequencing and conventional karyotype. METHODS: Bone marrow (BM) and abdominal mass biopsies from the patient were evaluated with extensive immunohistochemical, flow cytometric, cytogenetic, and molecular studies. RESULTS: The patient was a female infant who presented between 2 and 5 months of age with cytopenias and an enlarging abdominal mass. Blasts in the BM and abdominal mass expressed CD71 and CD117 with focal expression of CD43, E-cadherin, epithelial membrane antigen, and hemoglobin A. They were negative for additional myeloid, lymphoid, and nonhematolymphoid markers. These findings were most consistent with PEL and erythroblastic sarcoma. RNA sequencing revealed the novel NFIA-RUNX1T1 fusion. CONCLUSIONS: Along with the previously reported PELs with NFIA-CBFA2T3 fusions, we describe a subset of PELs that occur in children, that frequently display extramedullary disease, and that harbor rearrangements of NFIA with core binding factor genes. We hypothesize that, together, these cases represent a rare but distinct clinicopathologic group of pediatric PELs with recurrent genetic abnormality.
Assuntos
Leucemia Eritroblástica Aguda/genética , Fatores de Transcrição NFI/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Feminino , Humanos , Lactente , Leucemia Eritroblástica Aguda/patologia , Fusão Oncogênica/genética , Translocação GenéticaRESUMO
OBJECTIVE: To map the occurrence of amyloid types in a large clinical cohort using mass spectrometry-based shotgun proteomics, an unbiased method that unambiguously identifies all amyloid types in a single assay. METHODS: A mass spectrometry-based shotgun proteomics assay was implemented in a central reference laboratory. We documented our experience of typing 16,175 amyloidosis specimens over an 11-year period from January 1, 2008, to December 31, 2018. RESULTS: We identified 21 established amyloid types, including AL (n=9542; 59.0%), ATTR (n=4600; 28.4%), ALECT2 (n=511; 3.2%), AA (n=463; 2.9%), AH (n=367; 2.3%), AIns (n=182; 1.2%), KRT5-14 (n=94; <1%), AFib (n=71; <1%), AApoAIV (n=57; <1%), AApoA1 (n=56; <1%), AANF (n=47; <1%), Aß2M (n=38; <1%), ASem1 (n=34; <1%), AGel (n=29; <1%), TGFB1 (n=29; <1%), ALys (n=15; <1%), AIAPP (n=13; <1%), AApoCII (n=11; <1%), APro (n=8; <1%), AEnf (n=6; <1%), and ACal (n=2; <1%). We developed the first comprehensive organ-by-type map showing the relative frequency of 21 amyloid types in 31 different organs, and the first type-by-organ map showing organ tropism of 18 rare types. Using a modified bioinformatics pipeline, we detected amino acid substitutions in cases of hereditary amyloidosis with 100% specificity. CONCLUSION: Amyloid typing by proteomics, which effectively recognizes all amyloid types in a single assay, optimally supports the diagnosis and treatment of amyloidosis patients in routine clinical practice.
Assuntos
Amiloide/classificação , Amiloidose/diagnóstico , Espectrometria de Massas , Proteômica/instrumentação , Sequência de Aminoácidos , Amiloide/metabolismo , Amiloidose/metabolismo , Feminino , Humanos , Masculino , Estudos Retrospectivos , Distribuição por SexoRESUMO
Islands of CD123high cells have been commonly described in the bone marrow of patients with chronic myelomonocytic leukemia (CMML). Using a multiparameter flow cytometry assay, we detected an excess of CD123+ mononucleated cells that are lineage-negative, CD45+, CD11c-, CD33-, HLA-DR+, BDCA-2+, BDCA-4+ in the bone marrow of 32/159 (20%) patients. Conventional and electron microscopy, flow cytometry detection of cell surface markers, gene expression analyses, and the ability to synthesize interferon alpha in response to Toll-like receptor agonists identified these cells as bona fide plasmacytoid dendritic cells (pDCs). Whole-exome sequencing of sorted monocytes and pDCs identified somatic mutations in genes of the oncogenic RAS pathway in the two cell types of every patient. CD34+ cells could generate high amount of pDCs in the absence of FMS-like tyrosine kinase 3-ligand (FLT3L). Finally, an excess of pDCs correlates with regulatory T cell accumulation and an increased risk of acute leukemia transformation. These results demonstrate the FLT3L-independent accumulation of clonal pDCs in the bone marrow of CMML patients with mutations affecting the RAS pathway, which is associated with a higher risk of disease progression.
Assuntos
Células Dendríticas/patologia , Leucemia Mielomonocítica Crônica/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Medula Óssea/patologia , Células Dendríticas/metabolismo , Feminino , Humanos , Leucemia Mielomonocítica Crônica/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Prognóstico , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologiaAssuntos
Medula Óssea/patologia , RNA Helicases DEAD-box/genética , Mutação em Linhagem Germinativa , Mutação de Sentido Incorreto , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Idoso , Biomarcadores , Aberrações Cromossômicas , Humanos , Imuno-Histoquímica , Masculino , Transtornos Mieloproliferativos/terapiaRESUMO
OBJECTIVE: To assess the relationship between bone marrow (BM) biopsy operator experience and both specimen quality and ancillary testing utilization. PATIENTS AND METHODS: We evaluated all referred and in-house (IH) BM biopsy specimens obtained over a contiguous 6-week period from April 3, 2017, to May 19, 2017. The BM specimens were assessed for the length of interpretable marrow, and aspirates were assessed for the presence of spicules. Subgroup comparisons included IH BM obtained by a trained team of nurses within our institution, patients clinically referred (CR) to our institution with outside-obtained BM specimens, and outside pathologist-referred (PR) consultation cases. Ancillary study usage was compared between the first 100 cases of each group. RESULTS: A total of 1191 BM specimens were analyzed, including 600 IH, 288 CR, and 303 PR cases with biopsies and/or aspirates. The average interpretable biopsy lengths of IH, CR, and PR cases were 16.0 mm, 10.0 mm, and 7.0 mm, respectively (P<.001). World Health Organization-recommended length of 15 mm or more was achieved in 61.4%, 26.6%, and 19.1%, respectively (P<.001). Of the aspirates analyzed among IH, CR, and PR cases, 93%, 71.3%, and 73.5% contained spicules, respectively (P<.001). Use of immunohistochemistry, flow cytometry, karyotype, and fluorescence in situ hybridization was higher in CR and PR cases than in IH cases (all P<.05). The IH, CR, and PR cases used on average 1.5, 2.8, and 4.8 immunohistochemistry stains per case (P<.001). CONCLUSION: Having a dedicated team of BM biopsy operators is likely one factor contributing to improved BM biopsy quality and a reduced need for ancillary testing.
RESUMO
OBJECTIVES: Determine ancillary test utilization for the workup of isolated eosinophilia in otherwise morphologically unremarkable bone marrow (BM). METHODS: We evaluated BM ancillary testing performed in cases with isolated eosinophilia and otherwise morphologically unremarkable BM. Cases with abnormal morphology (eg, dysplasia, basophilia) and/or findings suggestive of a disorder (eg, unexplained thromboses, lymphoma) are specifically excluded. RESULTS: A total of 132 cases met inclusion criteria. Ten cases had an ancillary testing abnormality that warranted a more specific hematologic diagnosis: four cases of lymphocytic variant of hypereosinophilic syndrome, three cases of myeloid neoplasm with PDGFRA rearrangement, and one case each of myeloid neoplasm with PDGFRB rearrangement, chronic eosinophilic leukemia, and morphologically occult systemic mastocytosis. No cases revealed a cryptic PDGFRB or BCR/ABL1 rearrangement or JAK2 V617F mutation. CONCLUSIONS: Findings from our institutional experience support initial testing in isolated eosinophilia with otherwise unremarkable BM to include PDGFRA rearrangement, tryptase/CD25 immunohistochemistry, cytogenetics, and T-cell flow cytometry/receptor gene rearrangement. This approach achieves diagnostic quality and test utilization efficiency in our clinical practice.
Assuntos
Rearranjo Gênico , Síndrome Hipereosinofílica/diagnóstico , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Leucemia/diagnóstico , Mastocitose Sistêmica/diagnóstico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Triptases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Medula Óssea/patologia , Criança , Estudos de Coortes , Eosinofilia/patologia , Feminino , Humanos , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/patologia , Leucemia/genética , Leucemia/patologia , Masculino , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: Lymphoplasmacytic lymphoma (LPL) remains a poorly defined entity, even with the discovery of MYD88L265P mutations and association with Waldenström macroglobulinemia (WM). Among bone marrow (BM)-based, low-grade B-cell lymphoma with plasmacytic differentiation (LGBLPD) and immunoglobulin M (IgM) paraproteins, we sought to determine whether MYD88L265P defines a distinct entity and can help refine diagnostic criteria for LPL. METHODS: BMs diagnosed with LGBLPD or LPL and serum IgM paraprotein were studied (2007-2013). Clinicopathologic features were reviewed and specimens were tested for MYD88L265P. RESULTS: In total, 138 (87%) of 159 cases had MYD88L265P, and 158 of 159 were clinically considered WM. MYD88L265P cases had higher disease burden than MYD88WT. Features associated with MYD88L265P include increased mast cells and lymphocyte (not plasma cell)-predominant infiltrate. Hemosiderin, Dutcher bodies, and paratrabecular growth were not associated with MYD88L265P. CONCLUSIONS: Our data support a clinicopathologic approach to LPL diagnosis and recognition that it may manifest with varying morphologies, phenotypes, and molecular features.
Assuntos
Linfoma de Células B/genética , Fator 88 de Diferenciação Mieloide/genética , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Feminino , Humanos , Imunoglobulina M , Linfoma de Células B/classificação , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Paraproteínas , Estudos Retrospectivos , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Per the revised fourth edition World Health Organization classification of acute myeloid leukemia, pure erythroid leukemia is now the sole type of acute erythroid leukemia. The diagnosis of this rare entity is often challenging and the cytologic overlap with non-neoplastic (eg, megaloblastic anemia) and neoplastic entities (eg, other types of acute leukemia and non-hematopoietic malignancies) warrants a significant degree of clinical, laboratory, immunophenotypic, and genetic investigation. Given the limited number of reports of this rare and diagnostically challenging entity, we report detailed clinicopathologic characteristics from 15 patients, the largest series thus far, of primary de novo pure erythroid leukemia to provide further diagnostic insights into this entity and reveal strategies for making the diagnosis. We found that de novo pure erythroid leukemia is a disease of adults (median age 68 years), exhibits a striking male predominance, is universally associated with an abnormal karyotype and has an exceedingly poor overall median survival of 1.4 months. Given the general inability of immunophenotypic markers to discriminate neoplastic from non-neoplastic erythroid proliferations, key features identified in this study to help establish the diagnosis of pure erythroid leukemia and exclude mimickers include circulating pronormoblasts, clear-cut dysplasia in erythroid, granulocytic, and/or megakaryocytic lineage, utilization of a broad immunophenotypic panel, TP53 immunohistochemical positivity, and identification of a complex, often highly complex, karyotype. Given the gravity of a diagnosis of de novo pure erythroid leukemia, it should be rendered with utmost confidence.