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2.
Hum Pathol ; 142: 62-67, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37979953

RESUMEN

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.


Asunto(s)
Amiloidosis , Sistema Urinario , Masculino , Humanos , Próstata/patología , Rojo Congo , Amiloidosis/diagnóstico , Amiloidosis/patología , Amiloide , Sistema Urinario/patología , Diagnóstico Precoz
3.
Hum Pathol ; 139: 27-36, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37390975

RESUMEN

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.


Asunto(s)
Amiloidosis , Humanos , Amiloidosis/genética , Amiloidosis/diagnóstico , Amiloide/metabolismo , Tracto Gastrointestinal/patología , Rojo Congo , Biopsia
4.
Am J Clin Pathol ; 160(3): 303-313, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37203248

RESUMEN

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.


Asunto(s)
Amiloidosis , Prealbúmina , Masculino , Humanos , Estudios Retrospectivos , Proteómica/métodos , Cromatografía Liquida , Espectrometría de Masas en Tándem , Amiloidosis/diagnóstico , Amiloidosis/patología , Amiloide/análisis , Pene/química , Pene/patología , Queratinas
5.
Am J Surg Pathol ; 47(1): 74-80, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35968972

RESUMEN

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.


Asunto(s)
Amiloidosis , Fibrilación Atrial , Humanos , Proteómica , Bazo/cirugía , Bazo/patología , Estudios Retrospectivos , Amiloidosis/patología , Amiloide
6.
Cardiovasc Pathol ; 61: 107469, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36038051

RESUMEN

Herein we present a case of an 80-year-old gentleman who presented with exertional dyspnea status post aortic valve replacement with #23 Trifecta pericardial St. Jude aortic bioprosthetic valve (BV) 12 years prior. He subsequently underwent valve re-replacement due cusp calcification. Histologically, the surgically explanted BV revealed Congophilic deposits with birefringence under cross-polarized light. Extensive work-up identified no systemic source of amyloid in this patient. Liquid chromatography-tandem mass spectrometry-based (LC-MS/MS) proteomics showed the amyloid was composed of human-origin amyloid signature proteins (apolipoprotein A4, apolipoprotein E, serum amyloid P) and human-origin mu heavy chains. Background bovine collagen was also present. Transmission electron microscopy (TEM) showed collections of 7.5-10 nm nonbranching fibrils, consistent with amyloid. Using these techniques, we classified the amyloid as Mu heavy chain, deposition of which is highly unusual in BV. Finally, we provide a review of the literature regarding isolated amyloid deposition in BV.


Asunto(s)
Bioprótesis , Prótesis Valvulares Cardíacas , Masculino , Bovinos , Animales , Humanos , Anciano de 80 o más Años , Válvula Aórtica/cirugía , Cromatografía Liquida , Falla de Prótesis , Espectrometría de Masas en Tándem , Colágeno , Apolipoproteínas
7.
Amyloid ; 29(3): 156-164, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35135386

RESUMEN

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.


Asunto(s)
Neuropatías Amiloides Familiares , Amiloidosis , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Amiloide/análisis , Neuropatías Amiloides Familiares/patología , Proteínas Amiloidogénicas , Amiloidosis/patología , Médula Ósea/patología , Humanos , Estudios Retrospectivos
10.
Histopathology ; 78(3): 459-463, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33020971

RESUMEN

AIMS: To characterise the clinicopathological features of amyloidosis due to EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), a newly described amyloid type. METHODS AND RESULTS: We identified cases by searching the Mayo Clinic amyloid liquid chromatography and tandem mass spectrometry typing database for specimens with the universal amyloid signature proteins, abundant EFEMP1 spectra and absence of other specific amyloid precursor proteins. We also developed an immunohistochemical stain for EFEMP1 applicable to formalin-fixed tissue sections and performed electron microscopy in one case. We identified 33 specimens from 32 patients with EFEMP1 amyloid. Most patients were female (91%) with a mean age of 75 years, and most specimens (94%) were from the bowel. EFEMP1 amyloid was incidentally identified in specimens biopsied/resected for a variety of clinical indications. In bowel specimens, EFEMP1 amyloid involved blood vessels and interstitium of the lamina propria, submucosa and/or muscularis propria. Although the EFEMP1 deposits were weakly to moderately Congo red-positive with absent to weak birefringence, they were strongly positive for EFEMP1 by immunohistochemistry, had the characteristic fibrillar ultrastructure of amyloid and were readily identified by mass spectrometry. CONCLUSIONS: EFEMP1 amyloid is a recently described novel amyloid type that predominantly affects the bowel of elderly females. Because EFEMP1 amyloid is only weakly Congo red-positive, it may be overlooked without a high index of suspicion. However, its characteristic microanatomical distribution is highlighted by immunohistochemistry and its identity is readily confirmed by mass spectrometry. Based on its distinctive features, we propose that EFEMP1 amyloidosis be considered a new amyloid type.


Asunto(s)
Amiloidosis , Proteínas de la Matriz Extracelular/metabolismo , Tracto Gastrointestinal Inferior/patología , Anciano , Anciano de 80 o más Años , Amiloide/metabolismo , Amiloidosis/diagnóstico , Amiloidosis/patología , Femenino , Humanos , Inmunohistoquímica , Tracto Gastrointestinal Inferior/metabolismo , Masculino , Persona de Mediana Edad
11.
Mayo Clin Proc ; 95(9): 1852-1864, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32861330

RESUMEN

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.


Asunto(s)
Amiloide/clasificación , Amiloidosis/diagnóstico , Espectrometría de Masas , Proteómica/instrumentación , Secuencia de Aminoácidos , Amiloide/metabolismo , Amiloidosis/metabolismo , Femenino , Humanos , Masculino , Estudios Retrospectivos , Distribución por Sexo
13.
Clin Case Rep ; 7(1): 107-109, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30656020

RESUMEN

Lymphoma often presents with extranodal manifestations. However, pancreatic involvement resulting in pancreatitis is rare. CD20-negative variants of diffuse large B-cell lymphoma are also rare and are more likely to present with extranodal involvement. Lymphoma should be considered in patients presenting with pancreatitis without traditional risk factors.

14.
Mayo Clin Proc ; 93(11): 1692-1693, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30392556
15.
ACG Case Rep J ; 5: e32, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29721514

RESUMEN

Immunosuppressive medications, frequently used to treat inflammatory bowel disease, have been linked to the development of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD). We describe a case of an EBV-positive mucocutaneous ulcer involving the palate in an elderly woman with inactive Crohn's disease. This patient had been on high-dose azathioprine for a decade. Following diagnosis of her LPD and discontinuation of azathioprine, her oral ulcers resolved completely.

16.
Am J Surg Pathol ; 42(7): 843-854, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29762141

RESUMEN

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT. We evaluated PD-1 and PD-L1 expression by immunohistochemistry in 39 CLL/SLL, 15 DLBCL-RT, and 26 other DLBCL. In CLL/SLL, neoplastic B-cell PD-1 expression was weak and restricted to prolymphocytes/paraimmunoblasts within proliferation centers (PCs) and accentuated PCs of all sizes. Neoplastic B-cell PD-1 expression was highly prevalent and demonstrated increased intensity in DLBCL-RT, but in contrast was only rarely seen in other DLBCL (12/15 vs. 1/26; P<0.0001). An excellent correlation (90% concordance) was observed between neoplastic B-cell PD-1 immunohistochemistry positivity and molecularly defined CLL/SLL clonal relatedness in DLBCL-RT. PD-L1 expression was observed on the neoplastic B cells in rare DLBCL-RT and other DLBCL cases (1/15 vs. 1/26; P>0.05) as well as background histiocytes and dendritic cells. Overall survival of DLBCL-RT was significantly inferior to that of the other DLBCL (median, 16.9 vs. 106.1 mo; P=0.002). Our findings suggest a biological continuum from prolymphocytes/paraimmunoblasts in CLL/SLL PCs to the neoplastic B-cells in DLBCL-RT. The characteristic PD-1 expression in DLBCL-RT makes it a potential surrogate marker for determining clonal relatedness to CLL/SLL, which may have important prognostic and therapeutic implications.


Asunto(s)
Linfocitos B/inmunología , Biomarcadores de Tumor/análisis , Transformación Celular Neoplásica/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Receptor de Muerte Celular Programada 1/análisis , Linfocitos B/patología , Antígeno B7-H1/análisis , Biomarcadores de Tumor/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Evolución Clonal , Análisis Mutacional de ADN , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Mutación , Fenotipo , Proteína p53 Supresora de Tumor/genética
17.
Artículo en Inglés | MEDLINE | ID: mdl-31723705

RESUMEN

Chronic otitis externa due to Mycobacterium tuberculosis complex is extremely rare and very few cases have been presented in the medical literature. We report here the case of an immunocompetent 68-year-old male with chronic auricular drainage, otalgia, hearing loss, external ear canal and tympanic membrane thickening for 3 years who was ultimately diagnosed with tuberculous chronic otitis externa on biopsy of external auditory canal granulation tissue using molecular diagnostic techniques. Later, sputum cultures were positive for Mycobacterium tuberculosis complex indicating disseminated tuberculosis. However, two plausible explanations could be pulmonary TB that disseminated to the ear canal with evidence of middle and outer otitis, or upper airway/nasopharyngeal involvement with direct extension into the middle and outer ear canals. Although extremely rare, extrapulmonary laryngeal head and neck tuberculosis should be considered in immunocompetent patients who present with chronic otitis without prior known exposure to tuberculosis when they fail standard therapy and in whom no other microbiologic cause can be identified.

20.
Am J Surg Pathol ; 40(1): 36-43, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26379151

RESUMEN

Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study.


Asunto(s)
Biomarcadores de Tumor/genética , Fosfatasas de Especificidad Dual/genética , Reordenamiento Génico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patología , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética , Proteínas Tirosina Quinasas Receptoras/genética , Adolescente , Adulto , Anciano , Quinasa de Linfoma Anaplásico , Biopsia , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma Anaplásico de Células Grandes/enzimología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Adulto Joven
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