bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterotopic High-Grade Salivary duct Carcinoma Likely Arising within Cervical Lymph Nodes
Authors: Asad M , Gupta G , Sieber S C 
Published: October 2024

Abstract

Introduction/Objective
Salivary duct carcinoma arising in heterotopic salivary gland tissue is an extremely rare occurrence, with less than five cases reported in the literature. We present a unique case of heterotopic high-grade salivary duct carcinoma likely arising within cervical lymph nodes.

Methods/Case Report
A 56-year-old male presented with enlarged cervical lymph nodes for few months. Physical examination was unremarkable. Computerized tomography (CT) scan of head and neck showed two enlarged level 1B lymph nodes, measuring 1.0 and 1.4 cm, with unremarkable salivary glands. Patient had left cervical level II lymph node biopsy that showed metastatic poorly differentiated carcinoma. Immunohistochemically, the tumor cells were positive for GATA3, cytokeratin 903, androgen receptor, p16 (variable nonspecific), and were negative for TTF-1, p40, p63, ER, PR and NKX3.1, favoring salivary gland ductal carcinoma. Positron emission tomography (PET) CT scan showed a hypermetabolic left submandibular gland and level 2A lymph nodes. Subsequently, the patient underwent left modified radical neck dissection. Sectioning of the submandibular gland revealed no discrete lesions. Multiple, firm to rubbery lymph nodes ranging from 0.4 cm to 2.3 cm, with tan-pink cut surfaces were identified. Microscopic examination showed normal submandibular salivary gland parenchyma. However, eight out of nineteen lymph nodes were positive for metastatic high-grade salivary duct carcinoma comprising tumor cells forming nests and cords with ample eosinophilic cytoplasm, pleomorphic round to oval nuclei and numerous mitotic figures. Several benign and malignant lymph nodes in levels I, II and IV showed heterotopic salivary gland tissue. Immunohistochemical stains for androgen receptor and p40 were positive and negative respectively, supported the final diagnosis of high-grade salivary duct carcinoma.

Results (if a Case Study enter NA)
NA

Conclusion
Given the absence of carcinoma in the completely sampled submandibular gland, the origin of the intra- nodal tumor deposits was most likely to be heterotopic salivary gland tissue. This case emphasizes the importance of meticulous pathological sampling required for definitive diagnosis.
DICER-1 Mutation Associated Sarcoma of Thyroid in An Adult Male
Authors: MAHESHWARI T , Carithers P , Kaur N , Manucha V 
Published: October 2024

Abstract

Introduction/Objective
DICER-1 is an autosomal dominant tumor predisposition syndrome caused by germline DICER1 mutations. In the thyroid, it is associated with an early-onset multinodular goiter (MNG) and low-grade thyroid carcinomas. The aggressive variants thyroblastoma and poorly differentiated carcinoma are however seen in the pediatric age group. We report a case of DICER-1-associated (rhabdomyo) sarcoma without primitive components in an adult male.

Methods/Case Report
A 44-year-old healthy male with a family history of MNG, presented with a large left neck mass confirmed on imaging with largest 6.4cm, and extension into the mediastinum. FNA showed a malignant spindle cell- rich neoplasm with negative expression for Keratins, TTF-1, PAX-8, Calcitonin, INSM- 1 and SOX-10. The CEA and calcitonin were normal. The lymphoma was excluded by flow cytometry. The patient underwent a left thyroidectomy with central and left selective neck dissection. On gross examination, the left lobe of the thyroid was replaced by a tan- white, partially encapsulated solid mass. Microscopic examination revealed nests and sheets of ovoid to spindle- shaped cells with eosinophilic cytoplasm in fascicles with hypocellular areas with loose stroma. Foci of rhabdomyoblastic differentiation with straps cells, positive for desmin and myogenin were identified. Brisk mitotic activity and tumor necrosis were present. No primitive thyroid epithelium or blastemal component was identified.
Tumor cells were negative for S100, SOX10 CD34, CD31, SMA, calponin, CD99, NKX2.2, SS18-SSX which excluded malignant peripheral nerve sheath tumor, angiosarcoma, leiomyosarcoma, Ewing’s sarcoma, and synovial sarcoma. Next-generation sequencing showed a DICER1 c.4517G&gt;A (p.W1506) and c.5437G&gt;C (p.E1813Q) mutation, both variants reported as germ-line variants. A final diagnosis of DICER-1-associated rhabdomyosarcoma was rendered. The patient underwent rehabilitation at another facility and lost to follow-up.

Results (if a Case Study enter NA)
NA

Conclusion
The case highlights the expanding spectrum of DICER-1-associated malignant tumors and the importance of keeping it in the differential diagnosis of unusual malignant tumors of the thyroid even in adults.
Evaluation of the Hematology Analyzer Test Performance Using Six Sigma Metrics: A Cross Sectional Study
Authors: Dy P R , Damian K B , Villanueva E Q 
Published: October 2024

Abstract

Introduction/Objective
The six sigma metric is used to assess the performance of a measurement procedure in comparison to the medical requirement. In clinical laboratories, it can be used to assess the quality of instruments or processes. This study aims to evaluate the performance of hematology analyzers using the six sigma scale.

Methods/Case Report
This is a descriptive cross-sectional study wherein quality control data from hematology analyzers were obtained. The mean, standard deviation, coefficient of variation, bias and sigma value of the RBC, WBC, hemoglobin, hematocrit, and platelet parameters were determined and the performance of Beckman Coulter DxH 900 was assessed by plotting a normalized OPSpecs chart.

Results (if a Case Study enter NA)
The WBC and platelet parameters had sigma values of more than 6. Less stringent quality control measures could be applied these parameters which include fewer Westgard rules and fewer control runs. The RBC and hemoglobin parameters had sigma values of at least 3. The hematocrit parameter had a sigma value of less than 3. Improving this parameter could be done by performing optical channel evaluation, using multiple Westgard control rules, increasing the number of control materials and the number of runs.

Conclusion
This study has demonstrated the analytical performance of hematology analyzers on the six sigma scale, which in turn allows for the selection of the appropriate statistical quality control rule. Ultimately, statistical quality control is only one part of a laboratory’s quality management system. The sigma quality of the testing process, as well as choosing the appropriate control rules and number of controls, may provide the basis for the total quality control strategy of the laboratory. Other pre-analytic and post-analytic factors must also be considered in formulating a laboratory total quality control plan. This would allow the laboratory to provide the best possible quality of services to its clients by increasing efficiency, reducing wastage, and incorporating continuous changes to improve the system.
The Impact of Pre-biopsy Corticosteroids Use on CD20 Staining Pattern in B-cell Lymphomas
Authors: Li X , Krishnamurthy K , Choudhuri J , Wang Y 
Published: October 2024

Abstract

Introduction/Objective
Diffuse large B-cell lymphomas, the most common Non-Hodgkin’s lymphoma are heterogeneous in terms of varied clinical presentation. The pathological work up these lymphomas is usually initiated with a CD20/CD3 immunohistochemical panel. Due to the aggressive nature of these lymphomas, pre-diagnosis corticosteroids are necessitated in some cases. However, the corticosteroids treatment can significantly alter the antigen staining of the lymphoma delaying the pathological diagnosis and subsequent treatment. This study investigates how pre-biopsy corticosteroids administration affects CD20 staining in B-cell lymphoma cells along with CD3 and PAX5, aiming to provide insights to the practicing pathologist for prompter diagnosis in these challenging cases.

Methods/Case Report
14 biopsy cases of B-cell lymphoma pretreated with corticosteroids were included in this study. Clinicopathological parameters including corticosteroids usage are collected. H&E and immunohistochemistry slides were reviewed to analyze CD20, CD3 and PAX5 staining patterns.

Results (if a Case Study enter NA)
Of 14 cases, 10 cases showed cytoplasmic and granular staining with CD20, with extracellular spilling instead of the typical membranous pattern. This change was more frequent with intravenous dexamethasone (7/9) compared to oral prednisone (3/5), high dose (80%) compared to moderate and low dose (67%), short-term corticosteroids usage (86%) compared to intermediate-term and long-term (57%) usage and shorter dosing interval (100% in Q6H). The impact of prebiopsy corticosteroids was seen more on lymph node (5/7) compared to bone marrow (3/5). This cytoplasmic granularity was also observed in CD3 in the background non-neoplastic T lymphocytes in 25% of the cases. Though nuclear stains such as PAX5, Ki67, MUM1 and BCL6 also showed granularity in a significant number of cases, it was limited to the nucleus.

Conclusion
Pre-biopsy corticosteroids leads to alteration in CD20 staining pattern of the lymphoma cells leading to cytoplasmic granularity with extracellular spillage, which causes diagnostic challenge. This effect varies according to the type, route, dose, and duration of corticosteroids usage.
A discussion of pediatric therapy-related acute myeloid leukemia with a rare t(8;16) translocation
Authors: Brown H , Leffew M , Stalling M 
Published: October 2024

Abstract

Introduction/Objective
Secondary acute myeloid leukemia is a type of blood cancer that arises after a previous myeloid neoplasm or after exposure to chemotherapy. Certain genetic mutations and chromosomal abnormalities can occur as a result of said cytotoxic drug-related effects. Here, we discuss a case of secondary acute myeloid leukemia with a rare translocation following hemophagocytic lymphohistiocytosis Etoposide treatment in a 13-year-old female. After less than a year into her initial treatment, the patient presented to the emergency department with severe bone pain. A full hematologic workup was performed, including bone marrow biopsy, flow cytometry analysis, and subsequent genetic studies. A diagnosis of therapy-related acute myeloid leukemia was made. Genetic studies revealed a rare t(8;16) translocation which presents with a unique morphology and prognosis that will be discussed here.

Methods/Case Report
A 13-year-old female presented to the emergency department for evaluation of fever, myalgia, and swelling in her clavicle. The patient’s history was notable for hemophagocytic lymphohistiocytosis with subsequent Etoposide chemotherapy treatment which she received less than a year prior to her visit. CBC was notable for low white blood cell count, low hemoglobin, increased neutrophilic bands, and decreased lymphocytes.
Given her past medical history and worsening pain without a clear reason, hematology was consulted.

Results (if a Case Study enter NA)
A blast count of 61.8% was reported via flow cytometry with the cells seen in the dim CD45+, moderate to bright side-scatter region, co-expressing CD4, CD14 (dim, heterogeneous), CD15, CD16 (dim), CD64, HLA-DR, and MPO. The bone marrow biopsy was described as hypercellular with the predominant cell type as blasts at 66.4%. Numerous hemophagocytic blasts were noted as well. Acute leukemia next generation sequencing panel revealed a t(8;16)(p11;p13.3) KATA6A::CREBBP fusion without other abnormalities in the evaluated genes. This workup as a whole rendered the diagnosis of acute myeloid leukemia with KAT6A::CREBBP.

Conclusion
Diagnosing acute myeloid leukemia with KATA6A::CREBBP is important for prognostic factors. Knowing the patient’s history regarding her prior chemotherapy with Etoposide is also imperative for distinguishing a de novo presentation of this rare subtype, versus a therapy-related myeloid neoplasm. The patient was started on chemotherapy for her acute myeloid leukemia shortly thereafter the diagnosis.
A Rare Case of Acute Promyelocytic Leukemia with Concomitant PML-RARA Fusion and TP53 Loss/ider(17)(q10)t(15;17) Showing Complete Clinical and Molecular response: A Case Report
Authors: Elkady M , Al-Quran S , Al-Kawaaz M , Kalantri S , Yasin H 
Published: October 2024

Abstract

Introduction/Objective
To report a case with rare cytogenetic abnormality: a patient with newly diagnosed acute promyelocytic leukemia (APL) with cytogenetic findings of t(15;17)(q24;q21), trisomy 8 and ider(17)(q10)t(15;17)-TP53 loss. The presence of isochromosome 17q may indicate the possibility of an unfavorable outcome. However, the case showed complete clinical and molecular response.

Methods/Case Report
A case of a 53-year-old female with history of ITP post-splenectomy presented with persistent hematuria, easy bruising, and worsening fatigue. She had mild microcytic anemia, moderate thrombocytopenia, 3% promyelocytes, and 14% blasts on differential CBC count. With increased PT, PTT, LDH, Uric acid and decreased fibrinogen level, APL was clinically suspected. The patient was initiated on all-trans retinoic acid (ATRA), allopurinol, and IV fluids. Bone marrow (BM) biopsy confirmed the diagnosis with unusual cytogenetic findings. The patient underwent induction and consolidation therapies (4 weeks each) with ATRA plus Arsenic Trioxide (ATO) and followed- up with a series of marrow biopsies, cytogenetic and molecular studies.

Results (if a Case Study enter NA)
The patient demonstrated complete clinical, histological, and molecular response. She tolerated the treatment without major side effects, showing improvement in CBC counts, coagulation profile and tumor lysis labs. Initial BM exam revealed hypercellularity with infiltrating sheets of atypical hypergranular promyelocytes (~80%) and minimal residual left trilineage hematopoiesis. Flow cytometry revealed a CD34 negative, CD117 variable abnormal promyelocyte population (~67% of total events). FISH was positive for PML/RARA translocation (15; 17) and TP53 loss. Karyotype showed 46,XX,der(15)t(15;17)(q24;q21),ider(17)(q10)t(15;17)[12]/47,idem,+8[9]. By the end of treatment, BM biopsy was normocellular with trilineage hematopoiesis and no definitive evidence of acute leukemia or increase in blasts. The Karyotype was normal. Quantitative PCR for PML-RARA was negative, indicating complete molecular remission.

Conclusion
In this unique case of APL with unusual cytogenetic abnormalities the literature demonstrates controversial data. The patient achieved complete clinical and molecular remission following standard treatment. This may indicate the limited prognostic significance of these additional cytogenetic abnormalities in this case.
Utility of MEF2B Immunohistochemistry in Distinguishing Follicular Lymphoma and Marginal Zone Lymphoma in Diagnostically Challenging Cases
Authors: Oyedeji O , King R , Dalland J C 
Published: October 2024

Abstract

Introduction/Objective
Distinguishing follicular lymphoma (FL) from marginal zone lymphoma (MZL) can be challenging, as the morphology and immunophenotype can overlap particularly in CD10-negative cases or those with marginal zone differentiation (MZD). MEF2B (Myocyte enhancer binding factor B) is a transcription factor that controls BCL6 expression in germinal center (GC) B-cells. Previous studies report MEF2B to have a high sensitivity and specificity for FL compared to other GC markers. We investigated the expression of MEF2B in low grade B cell lymphomas (LGBCL) to evaluate its utility in classifying diagnostically challenging cases and FL with MZD.

Methods/Case Report
Our archives were searched from 2005-2023 to identify excisional biopsies of LGBCL with MZD, including (FL), splenic MZL (SMZL), MZL of mucosa-associated lymphoid tissue (MALT), nodal MZL (NMZL) and difficult-to-classify (DTC) cases with a differential diagnosis of MZL and FL. MEF2B immunohistochemistry was performed retrospectively (Atlas Antibodies). Two hematopathologists assigned a pre-and post-MEF2B diagnosis to DTC cases.

Results (if a Case Study enter NA)
57 cases were included: 21 FL (12 with MZD), 11 SMZL, 13 MALT, 4 NMZL, and 8 DTC cases. 19/21 FL cases (90%) were positive for MEF2B, including 11/12 (92%) cases with MZD. However, MEF2B expression was restricted to the follicles and negative in MZD areas in 7/11 cases (64%), while 4 cases showed partial weak expression in the areas of MZD. 0/11 SMZL (0%), 0/13 MALT (0%), and 0/4 (0%) NMZL were positive for MEF2B. 6/8 DTC cases (75%) were positive for MEF2B. Within DTC cases, retrospective inclusion of MEF2B results helped to render a more definitive diagnosis in 5 cases (2 negative/3 positive).

Conclusion
MEF2B immunohistochemistry can aid in distinguishing FL from MZL in challenging cases. However, it is often negative in areas of FL with MZD so care must be taken on interpretation in small biopsies.
ALK-positive Anaplastic Large Cell Lymphoma Involving the Spinal Cord
Authors: Hwaung P , Tian D 
Published: October 2024

Abstract

Introduction/Objective
ALK-positive anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for approximately 3% of non-Hodgkin lymphoma cases in the adult population. Lymph node involvement is most commonly seen, followed by extra-nodal involvement of the skin, soft tissue, and bone. Central nervous system involvement is rare at the time of diagnosis. This case study features a patient with systemic ALK-positive ALCL involving multiple nodal and extra-nodal sites, most notably the spinal cord.

Methods/Case Report
A 22-year-old female presented to the hospital with worsening back pain accompanied by neurological symptoms. MRI scans of her spine revealed extensive patchy abnormal marrow signal with enhancement of the thoracolumbar vertebrae (T1-L2) and adjacent extension into the spinal canal (T3-T7, T10-L1, L3-S1) and paraspinal soft tissues. A laminectomy of the T5-T7 and T11-T12 levels was performed for surgical decompression, and epidural and paraspinal resection specimens were submitted. These specimens, along with an excisional axillary lymph node biopsy, demonstrated ALK-positive ALCL after comprehensive immunohistochemical studies. In-situ hybridization for EBV was negative. CHOP therapy was initiated, but treatment was complicated by Candidemia and disseminated intravascular coagulation. The patient rapidly declined and passed away less than a month after hospital admission.
At autopsy, enlargement of lymph nodes, the left ovary (17.8 g), and spleen (383.6 g) were noted on gross examination. A solid, white-tan lesion (2.1 x 0.9 x 0.8 cm) was found in the left ovary. Necrosis and infiltrates of large, pleomorphic lymphoid cells with irregular nuclear contours and prominent nucleoli were seen on microscopic examination of the spinal cord and leptomeninges, vertebral bone marrow, mediastinal lymph nodes, spleen, and left ovary. Consistent with previously submitted surgical specimens, the viable neoplastic cells stained strongly positive for ALK-1, CD4, and CD30.

Results (if a Case Study enter NA)
NA

Conclusion
This case study highlights an atypical presentation of ALCL with a fatal outcome. Given the availability of effective treatment options, prompt diagnosis is crucial to improving survival outcomes. Additional research is necessary to elucidate the clinical and pathological features of ALCL. The differential for back pain is broad, but including this entity for patients with similarly insidious clinical presentations can prevent a delay in diagnosis that allows for rapid progression of disease.
Case Series: Unveiling mass-forming neoplastic extramedullary hematopoiesis in chronic myeloid leukemia
Authors: Iashvili L , Christie-Nguyen P , Ibrahim N , Rivera D , mai B , Armstrong J A 
Published: October 2024

Abstract

Introduction/Objective
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by BCR::ABL1 fusion and predominantly granulocytic proliferation. Three main phases of disease have previously been recognized: chronic, accelerated and blast phase, though accelerated phase has become controversial. During the chronic phase, leukemic cells exist predominantly in the peripheral blood and bone marrow; however, during blast phase, blasts can proliferate in the blood, bone marrow, or extramedullary tissues.

Methods/Case Report
We present two instances of cutaneous extramedullary hematopoiesis associated with CML at our institution.

Results (if a Case Study enter NA)
Case 1: A 34-year-old man previously diagnosed with CML presented with painful pustules on his right thigh. Biopsy revealed an infiltration of primarily left-shifted granulocytes, along with scattered megakaryocytes, and rare erythroid precursors. Immunohistochemical studies were consistent with maturing extramedullary hematopoiesis, devoid of sheets or clusters of blasts. Peripheral blood analysis revealed marked neutrophilic leukocytosis with basophilia and eosinophilia. Bone marrow examination depicted left-shifted granulocytic hyperplasia, megakaryocytic hyperplasia, and fewer than 5% blasts.
Case 2: A 40-year-old man presented with fatigue, night sweats, weight loss, hepatosplenomegaly and palpable nodules on his left arm and thighs. The biopsy of the thigh nodule uncovered leukemic cells at different developmental stages, along with eosinophils, erythroid precursors, and megakaryocytes. Immunohistochemical staining confirmed their presence, with only a few blasts observed. Blood and bone marrow tests showed leukocytosis with blasts less than 5%, indicating CML in the chronic phase. Molecular analysis confirmed BCR-ABL1 fusion.

Conclusion
Mass-forming neoplastic extramedullary hematopoiesis in the skin during chronic phase of CML is a feature that is not well-documented in the literature. This entity shows immature granulocytic precursors, but does not exhibit an increase in blasts and therefore should not be called leukemia cutis or myeloid sarcoma. It is important to raise awareness of this entity to prevent misinterpretation as myeloid sarcoma and subsequent unnecessarily aggressive therapy.