Archives of pathology & laboratory medicine最新文献

Context.—: Distinguishing benign from malignant processes in small lung biopsy specimens is challenging, particularly in the presence of architectural distortion and crush artifacts. Mimics include reactive type II pneumocytes in peribronchiolar metaplasia or organizing pneumonia and benign mucinous elements, including goblet cells and submucosal glands, which can mimic adenocarcinoma with mucinous features.

Objective.—: To understand whether caudal-type homeobox 2 (CDX2) and cytokeratin 20 (CK20) immunoreactivity is specific to malignant epithelial processes and evaluate their expression in a range of benign, premalignant, and malignant pulmonary lesions.

Design.—: We assessed CDX2 and CK20 immunohistochemistry in 48 cases of interstitial lung disease with reactive type II pneumocytes, 13 foci of atypical adenomatous hyperplasia, 11 bronchiolar adenomas, 4 adenocarcinomas in situ, 25 minimally invasive adenocarcinomas, 39 pulmonary adenocarcinomas with mucinous features, 6 mucoepidermoid carcinomas, and 1 squamous papilloma with goblet cell hyperplasia.

Results.—: No expression of CDX2 or CK20 was observed in reactive processes, goblet cells, bronchial glands, atypical adenomatous hyperplasia, or bronchiolar adenomas. In adenocarcinomas with mucinous features (n = 39), 9 (23%) were CK20-reactive and 8 (20%) were CDX2-reactive. A minority of nonmucinous and mucinous minimally invasive adenocarcinomas (n = 25) showed immunoreactivity (3 [12%] for each marker), while all in situ adenocarcinomas were negative.

Conclusions.—: Our findings demonstrate that CDX2 and CK20 are not expressed in benign or reactive type II pneumocytes and are specific for malignancy, particularly adenocarcinomas with mucinous features. Immunoreactivity with either marker in small biopsy specimens can support a diagnosis of malignancy, especially in morphologically equivocal or limited samples. Absence of staining does not exclude malignancy, but immunoreactivity with CDX2 and/or CK20 provides strong supportive evidence for a malignant process.

Context.—: In April 1946, Archives of Pathology published H. G. Schlumberger's seminal study on anterior mediastinal (AM) teratomas that provided insights into the clinical behavior, pathologic features, and pathogenesis of these enigmatic neoplasms.

Objective.—: To review key points of Schlumberger's study, add more recent information, discuss the different types of mediastinal teratoma and germ cell tumors (GCTs), and consider the origin of the neoplasms.

Data sources.—: Schlumberger's article, PubMed-indexed articles on the topic, and personal observations.

Conclusions.—: Pure teratomas of the AM in children are benign type I GCTs that may dedifferentiate to yolk sac tumor, possibly from embryonic-type neuroectoderm. Mature teratomas in postpubertal patients, comprising ∼95% of GCTs in females but only ∼30% in males, are hybrid type I and type IV teratomas. Such cases show organoid structures and benign cytology. They derive from nontransformed germ cells and lack metastatic potential. Immaturity does not alter the outcome in children. In contrast, many teratomas in postpubertal males are type II GCTs, derived from malignantly transformed germ cells that initially form a primitive GCT, with subsequent teratomatous differentiation. These teratomas, consequently, are components of mixed GCTs and show cytogenetic abnormalities, including overrepresentation of chromosome arm 12p. They are cytologically atypical and less commonly organoid; their most frequent associated GCT is yolk sac tumor, which may be the source of somatic-type malignancies of type II AM GCTs, especially the virtually uniquely associated hematologic malignancies and vascular neoplasms of GCT origin. All AM GCTs are believed to derive from mismigrated germ cells.

Context.—: Thyroid gland neoplasia comprises the most common group of tumors arising within organs of the endocrine system. Pathogenic molecular changes can now be identified in up to 90% of thyroid carcinomas. These alterations not only shape our understanding of tumor biology and classification, but also increasingly guide therapeutic approaches to these diseases.

Objective.—: To revisit a frequently cited review article from 2011 that outlined fundamental differences between tumor types-primarily papillary thyroid carcinoma and follicular neoplasia-in terms of their underlying genetic profiles. The present review discusses the aspects of the preceding manuscript that have remained salient, as well as advances in thyroid molecular pathology that have transpired in the intervening years.

Data sources.—: Primary literature and review articles were evaluated in order to consider topics addressed in the original review, and to gauge progress that has occurred since its publication.

Conclusions.—: The distinction between the respective molecular signatures of papillary thyroid carcinoma and follicular neoplasia, and the specter of alterations associated with aggressive cancers, remain pertinent in the present era. Important changes since 2011 relate to the reorganization of diagnostic categories, the prospect of molecular alterations in (or their incompatibility with) nonneoplastic processes, and the variety of available molecular testing platforms. Molecular analysis of thyroid nodules now factors into every step along the gamut from initial assessment to definitive classification to subsequent guidance of management. Nikiforov's review established a conceptual framework around thyroid neoplasia that has evolved over time, but endures as the dominant paradigm regarding these tumors.

Context.—: Nearly a century has passed since a seminal review article was published in 1928 in Archives of Pathology on ectopic endometriosis, presenting the dominant pathogenetic theories of the era: the serosal theory suggesting that endometriosis would arise by metaplasia of the peritoneal mesothelium; the metastatic theory implying the role of uterine lymphovascular invasion by endometrial tissue; and the implantation theory. Since then endometriosis has been the subject of numerous studies due to the associated morbidity and its significant impact on patients' quality of life and health care costs.

Objective.—: To provide an overview of our evolving understanding of pathogenesis and clinicopathologic features of endometriosis.

Data sources.—: Review of the literature and personal experience of the authors.

Conclusions.—: The prevailing pathogenetic theory of endometriosis remains the retrograde menstruation and implantation theory proposed by Sampson in the 1920s. Contemporary studies have focused on the additional role of inherited genetic components, a supportive microenvironment, and molecular genetic alterations to improve the clinical classification, prognostication, and therapeutic options for patients with endometriosis.

Context.—: Irving M. Ariel, MD, a pathologist at Mount Sinai Hospital in New York, published an article on small bowel neuroendocrine tumor (SB-NET) in the Archives of Pathology in 1939 titled "Argentaffin (Carcinoid) Tumors of the Small Intestine: Report of 11 Cases and Review of Literature," wherein he documented 11 cases of neuroendocrine tumors. SB-NET has since evolved in all aspects from terminology to treatment.

Objective.—: To review the current literature on SB-NET to study the new breakthroughs of these tumors with reference to Dr Ariel's 1939 paper.

Data sources.—: The literature was reviewed to study the recent advances of SB-NET.

Conclusions.—: We found that Dr Ariel's paper stood the test of time even with all the modern innovations in the pathophysiology of SB-NET.

Context.—: Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare but serious inflammatory heart diseases that pose significant diagnostic and therapeutic challenges. The relationship between the 2 has been debated for decades, sparked in part by a 1980 study using immunohistochemistry and electron microscopy to examine their histopathologic overlap.

Objective.—: To review and synthesize the historical, pathologic, clinical, and molecular understanding of GCM, explore its overlap and distinctions with CS, and outline future directions for diagnosis and treatment.

Data sources.—: Historical literature, clinicopathologic studies, imaging studies, and molecular research including transcriptomic and proteomic analyses.

Conclusions.—: GCM is characterized by a fulminant clinical course, diffuse myocardial necrosis with multinucleated giant cells and eosinophilic infiltrate, and a predominantly CD8+ T-cell response. In contrast, CS typically presents with more indolent cardiac symptoms, well-formed nonnecrotizing granulomas with Langhans-type giant cells, and a CD4+ T-cell predominant response. GCM and CS share overlapping clinical and imaging features, and sometimes have histopathologic similarities as well. Emerging molecular data suggest transcriptional differences, but a subset of cases exhibit mixed or intermediate features, suggesting a possible disease spectrum. Advances in molecular profiling, standardized diagnostic criteria, noninvasive imaging modalities, and targeted immunosuppression may help refine diagnosis and treatment. Clarifying whether these conditions lie along a shared pathobiologic continuum remains an important goal for future research.

Context.—: In 1954 Godman and Churg published an article in the Archives of Pathology & Laboratory Medicine entitled "Wegener's Granulomatosis" (now replaced by "granulomatosis with polyangiitis" [GPA]) and linked various forms of what is currently recognized as pauci-immune small-vessel vasculitis.

Objective.—: To put the 1954 article by Godman and Churg into context and review current ideas of GPA.

Data sources.—: Published literature.

Conclusions.—: Godman and Churg proposed the name Wegener's granulomatosis and defined the essential features as granulomatous inflammation and necrotizing vasculitis involving, typically, the upper respiratory tract, lung, and kidney. They suggested that GPA, allergic angiitis, and granulomatosis (later known as Churg-Strauss syndrome, now "eosinophilic granulomatosis with polyangiitis" [EGPA]), and what were referred to as "microscopic forms of periarteritis nodosa," now "microscopic polyangiitis," were related entities producing small-vessel vasculitis. We currently recognize these diseases as the spectrum of pauci-immune ANCA (anti-neutrophil cytoplasmic antibody)-associated small-vessel vasculitis, in contrast to small-vessel vasculitis characterized by immune complex deposits. ANCAs are antibodies directed against the neutrophil proteins proteinase 3 (PR3, usually associated with GPA) and myeloperoxidase (MPO, usually associated with microscopic polyangiitis and EGPA). A modern definition of GPA discloses that it can affect any organ in the body, characteristically with upper respiratory tract involvement. In the lung it is associated with necrotizing nodules and/or capillaritis with hemorrhage. It has been proposed that these forms of vasculitis should in the future be primarily classified by using ANCA specificity-that is, PR3 or MPO-as a disease definition, based on observations that the type of ANCA is what determines the location/pattern of organ involvement.

Context.—: The role of anti-phospholipase A2 receptor (PLA2R) antibody (PLA2R-immunoglobulin [Ig] G) in management of membranous nephropathy (MN) is important. However, information regarding the value of its main subtype, PLA2R-IgG4, is limited.

Objective.—: To evaluate the diagnostic value and clinical significance of serum and urine PLA2R-IgG4 in MN.

Design.—: Patients with biopsy-confirmed MN and other glomerulopathies were enrolled. PLA2R-IgG and PLA2R-IgG4 were measured. Diagnostic performance and clinical significance were further analyzed.

Results.—: A total of 406 patients were enrolled. The areas under the receiver operating characteristic curve (AUC) for serum PLA2R-IgG detected by enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay were comparable and demonstrated good agreement. The AUC for serum PLA2R-IgG4 was 0.853. At a cutoff of 147.51 ng/mL, sensitivity was 66.45%, which was higher than that for PLA2R-IgG detected by enzyme-linked immunosorbent assay (46.77%) and for PLA2R-IgG detected by time-resolved fluoroimmunoassay (51.95%). Serum PLA2R-IgG4 was correlated inversely with albumin (r = -0.39, P < .001), and positively with creatinine (r = 0.20, P < .001) and proteinuria (r = 0.33, P < .001). The AUC for urine PLA2R-IgG4/Cr was 0.754. Urine PLA2R-IgG4/Cr showed positive correlation with 24-hour proteinuria (r = 0.50, P < .001) and negative correlations with serum albumin (r = -0.58, P < .001) and serum creatinine (r = -0.27, P < .001). In patients presenting with nephrotic syndrome, the urine PLA2R-IgG4/Cr showed an equal diagnostic performance to that of serum PLA2R-IgG4 (AUC = 0.916 versus 0.940, P = .24).

Conclusions.—: Serum PLA2R-IgG4 further enhanced diagnostic sensitivity. Urine PLA2R-IgG4 had an excellent diagnostic performance in patients with nephrotic syndrome and demonstrated superior correlation with clinical disease activity.