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Blood Apr 2020Castleman disease (CD) describes a group of at least 4 disorders that share a spectrum of characteristic histopathological features but have a wide range of etiologies,... (Review)
Review
Castleman disease (CD) describes a group of at least 4 disorders that share a spectrum of characteristic histopathological features but have a wide range of etiologies, presentations, treatments, and outcomes. CD includes unicentric CD (UCD) and multicentric CD (MCD), the latter of which is divided into idiopathic MCD (iMCD), human herpes virus-8 (HHV8)-associated MCD (HHV8-MCD), and polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS)-associated MCD (POEMS-MCD). iMCD can be further subclassified into iMCD-thrombocytopenia, ascites, reticulin fibrosis, renal dysfunction, organomegaly (iMCD-TAFRO) or iMCD-not otherwise specified (iMCD-NOS). Advances in diagnosis, classification, pathogenesis, and therapy are substantial since the original description of UCD by Benjamin Castleman in 1954. The advent of effective retroviral therapy and use of rituximab in HHV8-MCD have improved outcomes in HHV8-MCD. Anti-interleukin-6-directed therapies are highly effective in many iMCD patients, but additional therapies are required for refractory cases. Much of the recent progress has been coordinated by the Castleman Disease Collaborative Network (CDCN), and further progress will be made by continued engagement of physicians, scientists, and patients. Progress can also be facilitated by encouraging patients to self-enroll in the CDCN's ACCELERATE natural history registry (#NCT02817997; www.CDCN.org/ACCELERATE).
Topics: Animals; Castleman Disease; Herpesviridae Infections; Herpesvirus 8, Human; Humans; Immunologic Factors; Interleukin-6; Rituximab
PubMed: 32106302
DOI: 10.1182/blood.2019000931 -
Endocrine Pathology Mar 2022The new WHO classification of adrenal cortical proliferations reflects translational advances in the fields of endocrine pathology, oncology and molecular biology. By... (Review)
Review
The new WHO classification of adrenal cortical proliferations reflects translational advances in the fields of endocrine pathology, oncology and molecular biology. By adopting a question-answer framework, this review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies that are now reflected in the 2022 WHO classification. The pathological correlates of adrenal cortical proliferations include diffuse adrenal cortical hyperplasia, adrenal cortical nodular disease, adrenal cortical adenomas and adrenal cortical carcinomas. Understanding germline susceptibility and the clonal-neoplastic nature of individual adrenal cortical nodules in primary bilateral macronodular adrenal cortical disease, and recognition of the clonal-neoplastic nature of incidentally discovered non-functional subcentimeter benign adrenal cortical nodules has led to redefining the spectrum of adrenal cortical nodular disease. As a consequence, the most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease which now includes (a) sporadic nodular adrenocortical disease, (b) bilateral micronodular adrenal cortical disease, and (c) bilateral macronodular adrenal cortical disease (formerly known primary bilateral macronodular adrenal cortical hyperplasia). This group of clinicopathological entities are reflected in functional adrenal cortical pathologies. Aldosterone producing cortical lesions can be unifocal or multifocal, and may be bilateral with no imaging-detected nodule(s). Furthermore, not all grossly or radiologically identified adrenal cortical lesions may be the source of aldosterone excess. For this reason, the new WHO classification endorses the nomenclature of the HISTALDO classification which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production to help predict the risk of bilateral disease in primary aldosteronism. Adrenal cortical carcinomas are subtyped based on their morphological features to include conventional, oncocytic, myxoid, and sarcomatoid subtypes. Although the classic histopathologic criteria for diagnosing adrenal cortical carcinomas have not changed, the 2022 WHO classification underscores the diagnostic and prognostic impact of angioinvasion (vascular invasion) in these tumors. Microscopic angioinvasion is defined as tumor cells invading through a vessel wall and forming a thrombus/fibrin-tumor complex or intravascular tumor cells admixed with platelet thrombus/fibrin. In addition to well-established Weiss and modified Weiss scoring systems, the new WHO classification also expands on the use of other multiparameter diagnostic algorithms (reticulin algorithm, Lin-Weiss-Bisceglia system, and Helsinki scoring system) to assist the workup of adrenal cortical neoplasms in adults. Accordingly, conventional carcinomas can be assessed using all multiparameter diagnostic schemes, whereas oncocytic neoplasms can be assessed using the Lin-Weiss-Bisceglia system, reticulin algorithm and Helsinki scoring system. Pediatric adrenal cortical neoplasms are assessed using the Wieneke system. Most adult adrenal cortical carcinomas show > 5 mitoses per 10 mm and > 5% Ki67. The 2022 WHO classification places an emphasis on an accurate assessment of tumor proliferation rate using both the mitotic count (mitoses per 10 mm) and Ki67 labeling index which play an essential role in the dynamic risk stratification of affected patients. Low grade carcinomas have mitotic rate of ≤ 20 mitoses per 10 mm, whereas high-grade carcinomas show > 20 mitoses per 10 mm. Ki67-based tumor grading has not been endorsed in the new WHO classification, since the proliferation indices are continuous variables rather than being static thresholds in tumor biology. This new WHO classification emphasizes the role of diagnostic and predictive biomarkers in the workup of adrenal cortical neoplasms. Confirmation of the adrenal cortical origin of a tumor remains a critical requirement when dealing with non-functional lesions in the adrenal gland which may be mistaken for a primary adrenal cortical neoplasm. While SF1 is the most reliable biomarker in the confirmation of adrenal cortical origin, paranuclear IGF2 expression is a useful biomarker in the distinction of malignancy in adrenal cortical neoplasms. In addition to adrenal myelolipoma, the new classification of adrenal cortical tumors has introduced new sections including adrenal ectopia, based on the potential role of such ectopic tissue as a possible source of neoplastic proliferations as well as a potential mimicker of metastatic disease. Adrenal cysts are also discussed in the new classification as they may simulate primary cystic adrenal neoplasms or even adrenal cortical carcinomas in the setting of an adrenal pseudocyst.
Topics: Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenocortical Adenoma; Adrenocortical Carcinoma; Adult; Child; Humans; World Health Organization
PubMed: 35288842
DOI: 10.1007/s12022-022-09710-8 -
Blood Research Apr 2023Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by... (Review)
Review
Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by ineffective clonal hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity for leukemia transformation. The identification of driver mutations in , , and has contributed to a better understanding of disease pathogenesis and has led to the development of MF-specific therapies, such as JAK2 inhibitors. Despite the fact that ruxolitinib and fedratinib have been clinically developed and approved, their use is limited due to adverse effects such as anemia and thrombocytopenia. Recently, pacritinib has been approved for a group of thrombocytopenic patients with significant unmet clinical needs. In symptomatic and anemic patients with prior JAK inhibitor exposure, momelotinib was superior to danazol in preventing exacerbation of anemia and in controlling MF-associated signs and symptoms, such as spleen size. Although the development of JAK inhibitors is remarkable, modifying the natural course of the disease remains a priority. Therefore, many novel treatments are currently under clinical development. Agents targeting bromodomain and extra-terminal protein, anti-apoptotic protein Bcl-xL, and phosphatidylinositol-3-kinase delta have been studied in combination with JAK inhibitors. These combinations have been employed in both the frontline and "add-on" approaches. In addition, several agents are being studied as monotherapies for ruxolitinib-resistant or -ineligible patients. We reviewed several new MF treatments in the advanced stages of clinical development and treatment options for cytopenic patients.
PubMed: 36891574
DOI: 10.5045/br.2023.2023012 -
Hematology/oncology Clinics of North... Dec 2022Patients with sickle cell disease and/or (rarely) trait are at increased risk for developing recurrent episodes of priapism, also known as stuttering priapism, and major... (Review)
Review
Patients with sickle cell disease and/or (rarely) trait are at increased risk for developing recurrent episodes of priapism, also known as stuttering priapism, and major ischemic priapism. Treatment of acute ischemic priapism is reactive; whereas ideal management consists of preventative approaches to ultimately promote the best improvement in patient's quality of life. Leg ulcers in patients with sickle cell disease (SCD) are quite common, with ∼20 % of patients with HBSS reporting either having an active or a past ucler. They can be confused with venous ulcers, with lower extremity hyperpigmentation confounding further the diagnosis. Several factors believed to contribute to the development of leg ulcers in patients with SCD are discussed in this article. Sickle cell liver disease (SCLD) occurs because of a wide variety of insults to the liver that happen during the lifetime of these patients. SCLD includes a range of complications of the hepatobiliary system and is increasing in prevalence with the aging adult sickle population. Liver nodular regenerative hyperplasia (NRH) is more common than realized and underappreciated as a diagnosis and requires liver biopsy with reticulin staining. Undiagnosed, the insidious damage from liver NRH can lead to noncirrhotic portal hypertension or cirrhosis.
Topics: Humans; Male; Adult; Priapism; Quality of Life; Liver Diseases; Anemia, Sickle Cell; Leg Ulcer
PubMed: 36400538
DOI: 10.1016/j.hoc.2022.08.001 -
The Journal of Physiology Jul 1902
PubMed: 16992626
DOI: 10.1113/jphysiol.1902.sp000919 -
The Journal of Physiology Jan 1902
PubMed: 16992591
DOI: 10.1113/jphysiol.1902.sp000885 -
Indian Journal of Otolaryngology and... Apr 2004Hemangiopericytomas are very rare soft tissue tumors of vascular origin featurding pericyts distributed around vascular spaces. They have unpredictable biological...
Hemangiopericytomas are very rare soft tissue tumors of vascular origin featurding pericyts distributed around vascular spaces. They have unpredictable biological behavior and a high local recurrence rate. Silver reticulin stain is essential for their histologic diagnosis. Approximately one third occur in the head and neck. Metastases occurs in nearly one half of all cases. They are relatively radioresistant despite their great vascular component. Wide local excision of the lesion, whenever feasible and lifelong follow-up should be the treatment of choice.
PubMed: 23120063
DOI: 10.1007/BF02974328 -
Indian Dermatology Online Journal 2016Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining...
INTRODUCTION
Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done.
MATERIALS AND METHODS
A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for "melanoma," "melanocytic nevus," and "blue nevus". Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica(®) 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient.
RESULTS
Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern.
CONCLUSION
The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness.
PubMed: 26955582
DOI: 10.4103/2229-5178.174312 -
The American Journal of Pathology Nov 1930
PubMed: 19969932
DOI: No ID Found