Publications by authors named "Sam Sadigh"

Background: The long-term stability of allograft or native bone in facial vascularized composite allograft (fVCA) recipients is unclear. This study quantified long-term bone volume changes in facial transplants.

Methods: Computed tomography scans of eight fVCA recipients (2011-2023) were analyzed with Materialise Mimics.

View Article and Find Full Text PDF

Rejection monitoring in facial vascularized composite allotransplantation traditionally focuses on skin biopsies. However, mucosal rejection frequently presents with more pronounced signs of immune activity. To explore mechanistic differences between skin and mucosal rejection, rejection and nonrejection biopsies from allograft skin and oral mucosa of 9 facial vascularized composite allotransplantation recipients were retrospectively analyzed using histology, multiplex immunostaining, and gene expression profiling, with peripheral blood mononuclear cells quantified via mass cytometry.

View Article and Find Full Text PDF

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms.

View Article and Find Full Text PDF
Article Synopsis
  • A study was conducted to evaluate peripheral blood smear review practices among pathologists across various institutions, as standardized criteria for these reviews are lacking.
  • The survey, developed by the Society for Hematopathology, was answered by 137 out of 725 members, revealing that most pathologists analyze 5 to 20 smears daily and utilize clinical data in their reviews.
  • Results indicated a mix of laboratory-initiated and clinician-requested reviews, emphasized the importance of smear review in pathology training, and highlighted areas for potential improvements based on respondents' experiences.
View Article and Find Full Text PDF

Posttransplantation primary cutaneous T-cell lymphomas (PT-CTCL) are a rare complication of sustained immunosuppression in the posttransplant setting. When present, PT-CTCLs are typically EBV- and exhibit features of mycosis fungoides/Sézary syndrome or CD30+ lymphoproliferative disorders. We present a case of a 75-year-old individual who developed skin lesions 30 years after liver transplantation.

View Article and Find Full Text PDF

Indolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the gene.

View Article and Find Full Text PDF

Despite the apparent complexity of the molecular genetic underpinnings of myeloid neoplasms, most myeloid mutational profiles can be understood within a simple framework. Somatic mutations accumulate in hematopoietic stem cells with aging and toxic insults, termed clonal hematopoiesis. These "old stem cells" mutations, predominantly in the epigenetic and RNA spliceosome pathways, act as "founding" driver mutations leading to a clonal myeloid neoplasm when sufficient in number and clone size.

View Article and Find Full Text PDF
Article Synopsis
  • Classic Hodgkin Lymphoma (cHL) is characterized by the presence of rare malignant HRS cells within a dense T-cell rich immune environment, with approximately 25% of cases linked to the Epstein-Barr Virus (EBV).
  • Using advanced imaging techniques, researchers analyzed 20 cHL samples to identify key differences in the tumor microenvironment between EBV-positive and EBV-negative cases, noting variations in T-cell populations and their dysfunction.
  • The study highlights distinct transcriptomic profiles that affect HRS cell growth and T-cell interactions, emphasizing the importance of understanding virus-associated tumors for developing targeted therapies.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the immunological processes related to lymphadenopathy in facial transplant patients, focusing on how donor-derived lymph nodes contribute to these processes after vascularized composite allograft (VCA) transplantation.
  • It analyzes clinical and histological data from 9 patients, revealing that those who received donor lymph nodes developed bilateral lymphadenopathy, which resolved over time.
  • The findings indicate that an immunological response involving both donor and recipient lymphocytes occurs in the lymph nodes, suggesting a unique rejection mechanism that differs from typical skin rejection in transplant patients.*
View Article and Find Full Text PDF
Article Synopsis
  • - The study analyzed skin and blood/bone marrow samples from 17 patients with various cutaneous neoplasms, primarily focusing on cutaneous acute myeloid leukemia (c-AML) and different types of dendritic cell neoplasms.
  • - A significant finding was that many c-AML patients had shared clonal mutations between their skin and bone marrow, with 70% also showing mutations like NPM1 and KMT2A rearrangements.
  • - The results indicate that cutaneous and myeloid neoplasms share common genetic mutations, enhancing the understanding of the relationship between these skin manifestations and underlying blood disorders.
View Article and Find Full Text PDF
Article Synopsis
  • - Vascularized composite allotransplantation (VCA) is a new surgical method that helps treat severe injuries, such as losing limbs or facial injuries, by transplanting various tissue types like skin, bone, and muscle.
  • - The body's immune system often rejects VCA grafts, especially those with skin, due to their strong antigenicity, which challenges the balance between accepting and rejecting the transplant.
  • - Recent research is uncovering the immune cells involved in graft rejection, aiming to develop targeted therapies that could improve the management of VCA transplant patients and potentially reduce the need for lifelong immunosuppression.
View Article and Find Full Text PDF

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 and is associated with pronounced hematopathologic findings. Peripheral blood features are heterogeneous and very often include neutrophilia, lymphopenia, myeloid left shift, abnormally segmented neutrophils, atypical lymphocytes/plasmacytoid lymphocytes, and atypical monocytes. Bone marrow biopsies and aspirates are often notable for histiocytosis and hemophagocytosis, whereas secondary lymphoid organs may exhibit lymphocyte depletion, pronounced plasmacytoid infiltrates, and hemophagocytosis.

View Article and Find Full Text PDF
Article Synopsis
  • Targeted therapies for blastic plasmacytoid dendritic cell neoplasm (BPDCN) face challenges in distinguishing it from similar reactive plasmacytoid dendritic cells due to overlapping immunoprofiles, highlighting the need for new diagnostic markers.!*
  • A study involving 50 BPDCN cases and various controls utilized double-staining methods to evaluate immunohistochemical markers such as SOX4/CD123 and TCF4/CD56 for accurate diagnosis.!*
  • Results showed that SOX4/CD123 provided 100% sensitivity and 98% specificity for identifying BPDCN, while TCF4/CD56 also proved highly effective, establishing these as reliable markers for confirming BPDCN and detecting minimal disease
View Article and Find Full Text PDF

Aggressive subtypes of non-Hodgkin lymphoma may uncommonly be referred to clinical oncologists for treatment of acute leukemia, due to an elevated or rapidly rising white blood cell count (WBC), with circulating neoplastic cells that morphologically resemble leukemic blasts seen in acute myeloid or lymphoblastic leukemia. We describe six cases of non-Hodgkin lymphoma that mimicked acute leukemia and were identified in the pathology records of the Brigham and Women's Hospital. The patients were older adults (mean age 70 years), who presented with leukocytosis (mean 79.

View Article and Find Full Text PDF
Article Synopsis
  • - The study focuses on primary central nervous system anaplastic large cell lymphoma (ALCL), which is rare and primarily affects younger individuals, with age being a key factor in prognosis.
  • - Researchers conducted a comprehensive search and analysis of existing cases, identifying 3 new cases along with 31 from published reports, noting common symptoms like headaches and a male predominance.
  • - The findings highlight genetic abnormalities, including ALK rearrangement, providing valuable diagnostic insights into this rare lymphoma's characteristics and clinical implications.
View Article and Find Full Text PDF

Despite the apparent complexity of the molecular genetic underpinnings of myeloid neoplasms, most myeloid mutational profiles can be understood within a simple framework. Somatic mutations accumulate in hematopoietic stem cells with aging and toxic insults, termed clonal hematopoiesis. These "old stem cells" mutations, predominantly in the epigenetic and RNA spliceosome pathways, act as "founding" driver mutations leading to a clonal myeloid neoplasm when sufficient in number and clone size.

View Article and Find Full Text PDF

Background: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking.

Methods: Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer-related genes.

View Article and Find Full Text PDF

Follicular dendritic cell sarcoma (FDCS) is a rare entity which can share morphologic features with non-keratinizing squamous cell carcinoma. Recent reports suggest that up to half of FDCSs show immunohistochemical positivity for p16 (Zhang et al., in Hum Pathol 66:40-47, 2017), a stain that is conventionally used in the risk stratification of oropharyngeal squamous cell carcinoma (OPSCC).

View Article and Find Full Text PDF

Pulmonary adenomyomas are rare adenomyomatous hamartomas. In the few cases described in the literature, these benign tumors are encapsulated by lung parenchyma. We describe a case of a 59 year-old woman with acetylcholine receptor antibody-negative myasthenia gravis and a right cardiophrenic mass initially thought to be a thymoma.

View Article and Find Full Text PDF

Purpose Of Review: Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative, is a rare myelodysplastic/myeloproliferative neoplasm (MDS/MPN) characterized by leukocytosis, granulocytic dysplasia, and typically poor patient outcomes. Since its first description as a variant CML lacking the Philadelphia chromosome (Ph), the diagnostic criteria for aCML have evolved significantly. Nevertheless, distinguishing it from other Ph-negative myeloid neoplasms can still be very challenging, and given its generally worse prognosis, this is a clinically important distinction.

View Article and Find Full Text PDF

Objectives: To characterize the tumor microenvironment of testicular germ cell tumors (GCTs) using immunohistochemical markers.

Methods: Seventy-seven orchiectomies, including 36 nonmetastatic (NM) seminomas, 15 metastatic (M) seminomas, 13 nonmetastatic nonseminomatous germ cell tumors (NSGCTs), and 13 metastatic NSGCTs, were studied with PD-1, PD-L1, FOXP3, CD68, CD163, and mismatch repair (MMR) immunohistochemistry. FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) expressing CD68 and CD163 were enumerated.

View Article and Find Full Text PDF

Rosai-Dorfman disease (RDD) is an enigmatic histiocytic disorder classically diagnosed by a distinctive combination of pathological features: emperipolesis, or migration of intact haematological cells through the voluminous cytoplasm of lesional histiocytes, and expression of S100 by these histiocytes. The pathogenesis has long been elusive until the recent detection of recurrent and mutually exclusive mutations in several oncogenes in the mitogen-activated protein kinase (MAPK) pathway. Based on these findings, we investigated a cohort of 21 RDD patients and found that the lesional histiocytes in 86% (18/21) of patients exhibited strong and diffuse nuclear Cyclin D1 expression, which not only may provide a diagnostic marker for this sometimes pathologically challenging disease, but also probably reflects constitutive MAPK pathway activation because we additionally identified phosphorylated-ERK expression in 90% (19/21) of cases.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session5gmhgdtfor2bvv3llgjlvrbkq9ib5ttf): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once