Immunohistochemical expression of perforin in adult systemic lupus erythematosus associated macrophage activation syndrome: Clinicohematological correlation and literature review.

OBJECTIVE: To study the bone marrow (BM) immunohistomorphological characteristics in adult systemic lupus erythematosus (SLE) associated macrophage activation syndrome (SLE-MAS). MATERIALS AND METHODS: Immunohistochemical (IHC) expression of CD3, CD8, perforin (PFN), and CD163 was studied on BM trephine biopsies from 30 cytopenic adult SLE cases (male: female = 1:5, age; 24 years, range; 19-32) and compared them with ten age matched controls. Clinicopathological parameters were compared among the cases likely (L) or unlikely (U) to have MAS using probability scoring criteria. The best cut off laboratory parameters to discriminate between the two were obtained through receiver operator curve (ROC) analysis. RESULTS: MAS occurred in 12/30 (40%) cases and was more commonly associated with prior immunosuppressive therapy (p = .07), ≥ 3 system involvement (p = .09), lower fibrinogen (p < .01), increased triglyceride (p = .002), increased BM hemophagocytosis (p = .002), and higher MAS score [185 (176-203) vs. 105 (77-119), p < .01] than MAS-U subgroup. Although PFN+CD8+ T lymphocytes significantly decreased among cases than controls (p < .05), it was comparable between MAS-L and MAS-U subgroups. Fibrinogen (< 2.4 g/L, AUC; 0.93, p < .01), hemophagocytosis score (> 1.5, AUC; 0.71, p = .03), and an MAS probability score of ≥ 164 (AUC; 1, p < .01) discriminated MAS from those without MAS. CONCLUSION: We noted a decrease in perforin mediated CD8 + T cell cytotoxicity in SLE. Immunohistochemical demonstration of the same along with histiocytic hemophagocytosis on BM biopsy may be useful adjunct in early diagnosis and management of MAS in SLE.

Core-binding factor abnormalities involving chromosome 16 in acute myeloid leukaemia: prognostic and therapeutic implications.

Core-binding factor (CBF) abnormality-associated myeloid neoplasms incorporate acute myeloid leukaemia (AML) (CBF-AML) with translocation t(8;21)(q22;q22.1) (AML1/ETO fusion) and inv(16)(p13.1q22) or translocation t(16;16)(p13.1;q22) (CBFB/MYH11 fusion) abnormalities which confer a favourable prognosis following cytarabine-based induction chemotherapy. Accumulating evidence from the molecular studies have stratified CBF-AML into favourable and unfavourable subgroups based on the associated cooperating mutations that impact the outcome. We describe a case of acute myelomonocytic leukaemia with abnormal eosinophils (M4Eo) in a woman in her 20s who was found to have CBFß/MYH11 fusion along with mutated c-KIT (exon 17) and KRAS (exon 2) genes by next-generation sequencing. She had an aggressive clinical course following initiation of cytarabine-based induction chemotherapy. The underlying mutational landscape may significantly influence the biological behaviour of otherwise favourable risk of CBF-AML cases.

Gingival hyperplasia: An initial oral manifestation of acute myeloid leukemia.

Various systemic diseases can manifest oral signs and symptoms early, which may be crucial for diagnosis and outlining the treatment plan. This case report highlights the presentation of acute leukemia (a malignancy of white blood cells) in a young female. An 11-year-old girl presented with gingival overgrowth and bleeding from the gingiva, weakness, and recent history of weight loss. A detailed workup consisting of complete blood count, bone marrow examination, flow cytometric immunophenotyping, cytogenetics, and molecular studies were carried out. The investigations confirmed the infiltration of blast cells of myelomonocytic origin, and a confirmatory diagnosis of acute myeloid leukemia (French-American-British classification M5) was made. The patient was put on induction chemotherapy and responded well. She developed febrile neutropenia following chemotherapy, which was managed conservatively. Gingival overgrowth subsided after the chemotherapy, and at the time of discharge, she was asymptomatic and hemodynamically stable. The oral health-care professionals must recognize that gingival overgrowth/enlargement may represent an initial manifestation of an underlying systematic disease.

Coinfection of Melioidosis and Tuberculosis Causing Infective Lumbar Spondylodiscitis: A Rare Case Report.

CASE: A 63-year-old farmer who is a known diabetic and chronic alcoholic presented with lower back pain and neurological weakness of lower limbs present for the past 3 months. His acute phase reactants were very high, and magnetic resonance imaging displayed L4-L5 vertebral involvement with epidural, paravertebral, and bilateral psoas abscesses. Cultures of an ultrasound-guided aspiration from the psoas were positive for Burkholderia pseudomallei, and a nucleic acid amplification test also detected Mycobacterium tuberculosis. He underwent posterior decompression and fixation, and intraoperative biopsy confirmed a granulomatous reaction. He received appropriate antibiotics for both diseases. At 1 year, he showed healing on radiographic imaging, with independent ambulation status. CONCLUSION: The coexistence of melioidosis and tuberculosis is rare, and as far as we know, a case of infective spondylodiscitis has not been reported. In patients with infective spondylodiscitis, every attempt should be made to confirm the diagnosis before starting empirical antitubercular treatment (ATT).

Acute Myeloid Leukemia following Radioactive Iodine Therapy for Metastatic Follicular Carcinoma of the Thyroid.

Radioactive iodine (RAI) therapy is widely used and has an important role in the management of hyperthyroidism and thyroid malignancies. The development of acute or chronic leukemia is a very rare complication of RAI therapy. We report a case of metastatic Follicular thyroid cancer (FTC) who underwent total thyroidectomy followed by treatment with a cumulative dose of 1600 mCi of RAI (for 4 years) and by palliative radiotherapy for L4 spinal metastasis, later on, developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

Usefulness of Leucocyte Cell Population Data by Sysmex XN1000 Hematology Analyzer in Rapid Identification of Acute Leukemia.

Leukocyte cell population data (CPD) generated by hematology auto analyzers are reported to be useful in screening of sepsis patients. However, there is a paucity of literature highlighting the utility of CPD in screening of acute leukemias (AL). Leucocyte CPD obtained by Sysmex XN1000 hematology analyzer from 210 cases of ALs [22 acute promyelocytic leukemia (APL), 79 non-APL acute myeloid leukemia (non-APL-AML) and 109 acute lymphoblastic leukemia (ALL)] were compared with 100 healthy and 52 reactive controls. Receiver operator curves were drawn to determine the cut-off values of individual parameters. The regression equations combining the best parameters were then formulated to calculate a cut-off value for discrimination among AL subgroups and controls. Acute leukemias showed significant differences (p < 0.05) in various CPD parameters compared to control subjects. A combination of best CPD parameters discriminated ALs from healthy controls (cut off; 0.443, sensitivity of 94% and specificity of 91%), ALs from reactive controls (cut off; 0.576, sensitivity; 97%, specificity; 92%), APL from non-APL-AML (cut off; 0.174, sensitivity of 91% and specificity of 67%), and AML from ALL (cut off; 1.338, sensitivity; 86.1%, specificity; 75%). The CPD from Sysmex XN 1000 analyzer could be a useful tool in screening and lineage characterization of acute leukemias; particularly at centers where high-end technical expertise is still not available. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01488-9.

Cyclooxygenase 2 (Cox 2) Expression in Newly Diagnosed Plasma Cell Myeloma: A Clinicopathological and Immunohistochemical Study on 73 Cases from a Single Tertiary Care Center.

To study the cyclooxygenase 2 (Cox 2) expression in newly diagnosed plasma cell myeloma cases by immunohistochemistry (IHC) and correlate with clinicohematological characteristics. Immunohistochemical expression of Cox 2 on bone marrow trephine biopsy was studied in seventy-three newly diagnosed myeloma cases [56 males, 17 females, median age; 58 years (36-75)] and fifteen controls using SP21 clone antibody. A median immuno-score (proportion x intensity) stratified the entire cohort into low and high expressors. Cox 2 immunoexpression was compared and correlated with clinicolaboratory characteristics and marrow histomorphology and survival. Twenty one of 73 (38.7%) cases had a plasmablastic morphology whereas remainder fifty-two (61.3%) had a differentiated morphology. The Cox 2 expression was noted in 71/73 (97.2%) cases (median score = 127.3) and 15/15 (100%) controls. Low expressors was associated with higher circulating plasma cells, increased marrow tumor burden, blastic morphology, and lower proliferation index (p < 0.05) with a peculiar 'dot-block' cytoplasmic positivity (p < 0.001); whereas high expressors had thinned out bony trabeculae with granular cytoplasmic positivity with or without membrane accentuation (p < 0.001). Cox 2 expression had a weak negative correlation with tumor burden (r; -0.32, p = 0.01) and positive correlation with proliferation index (r; 0.29, p = 0.03). There was no statistically significant difference in the survival between low (n = 20) and high (n = 23) expressors (log rank p = 0.11). A high proportion of myeloma cells in our cohort expressed Cox 2 using SP21 clone; and this may have a role in futuristic research and therapy.

Eosinophilic Granuloma as a Solitary Lytic Lesion of the Cervical Spine in a Child.

Introduction: Eosinophilic granuloma (EG) is a type of Langerhan cell histiocytosis (LCH) with unknown etiology. This benign tumorous lytic lesion affects mainly children or young adults, causing bone destruction. Although, the flat or the long bones are commonly affected, localized spinal involvement in pediatric age group is rare. A thorough workup is therefore necessary for this condition, which may mimic other severe conditions. Case Report: A 10-year-old girl presented with neck pain for 4 months without any history of trauma, fever, or neurological weakness. An X-ray revealed radiolucency and sclerosis of the fifth cervical vertebral body, which was hypointense on T1 and heterogeneous on T2-weighted image, with mild peripheral enhancement on fat-suppressed post-contrast T1-weighted image. Biopsy histomorphology revealed a lymphohistiocytic lesion with scatted histiocytes with grooved nuclei, immunopositive for Langerin; thus consistent with LCH (EG). She was managed conservatively with a completely pain free course with full range of movement at 1-year follow-up. Her follow-up X-ray showed complete remodeling and ongoing fusion. Conclusion: EG should be considered as a differential diagnosis in the evaluation of solitary lytic lesion involving spine in pediatric age group. This, although self-resolving, may occasionally need surgical intervention with or without adjuvant therapy.

Primary gastrointestinal anaplastic large cell lymphoma: A critical reappraisal with a systematic review of the world literature.

Anaplastic large cell lymphoma (ALCL) is a distinct T-cell non-Hodgkin lymphoma involving both nodal and extra-nodal sites with a specific anaplastic lymphoma kinase 1 (ALK-1) gene rearrangement. The commonly involved extranodal sites include skin, bone, soft tissue, lungs, and liver. ALCL primarily involving gastrointestinal (GI) tract is rare. In this manuscript, we describe a case of primary esophageal ALK1 positive-ALCL (null phenotype) in a young female, who presented with fleshy mucosal lesion in the lower third of the esophagus and present a systematic review of 35 cases of GI-ALCL reported in the English literature over the past 28 years (1990-2018) with regard to the clinicopathological characteristics, therapy, and outcome.

Pulmonary anaplastic large-cell lymphoma: A case-based systematic review of world literature.

We describe a case of ALK1 negative (-) pulmonary anaplastic large-cell lymphoma (pALCL) in an adult female with an unfavorable outcome following combination chemotherapy and present a systematic review of 39 such sporadic cases reported over the past 28 years (1990-2018). pALCL occurred in 26 males and 13 females (median age, 43 years [5-81]) and 13/39 (33.33%) were ≤18 years. The lesions were endobronchial in 21 (53.85%) and parenchymal in 18 (46.15%) cases. Twenty-six cases were ALK1-; 13 were ALK1+ (positive); and 27/34 cases had a T cell phenotype (where tested). ALK- cases were characterized by higher age (P = 0.012) at presentation, more B symptoms (P = 0.002), and more parenchymal than endobronchial lesions (P = 0.039). The median survival (N = 29/39) was 60 months; pediatric group had a better survival than adult/elderly group (log-rank, P = 0.026). pALCL is rare and may have a distinct biological behavior.

Acquired Pure Red Cell Aplasia and Recombinant Erythropoietin.

Recombinant erythropoietin (rEPO)-associated immunologically driven acquired pure red cell aplasia (PRCA) is an underreported, potentially worsening clinical syndrome in the setting of treatment of anemia of chronic kidney disease. Most cases reported in world literature are related to different formulations of erythropoiesis-stimulating agents with an implication in diagnosis and management. This brief review highlights the clinical guidelines of rEPO usage in nephrology practice, the pathophysiologic mechanism of PRCA, clinical features, diagnosis, and suggested management protocols.

Clinicopathological and Immunohistochemical Profile of Mantle Cell Lymphoma: An Institutional Experience.

Introduction Mantle cell lymphoma (MCL) is a biologically aggressive B-cell non-Hodgkin lymphoma (NHL) with distinctive morphologic, immunophenotypic, and molecular characteristics. Differentiation from other chronic lymphoproliferative disorders is essential for prognostication. Aim This paper aims to study the clinicopathological features of MCL with emphasis on immunohistochemical features and disease correlation. Method To do so, clinicopathological characteristics from 21 cases of MCL (14 males, seven females, M:F=2:1) diagnosed in the last five years i.e. 2015 to 2020, were retrospectively reviewed and correlated with immunohistochemistry (IHC) data. Particularly those pertaining to cyclin D1, SRY-box transcription factor 11 (SOX11), cluster of differentiation (CD) 5, CD23, MIB E3 ubiquitin protein ligase 1 (MIB1), tumor protein 53 (TP53), c-myelocytomatosis oncogene product (c-MYC), multiple myeloma oncogene 1 (MUM1), mouse double minute 2 homolog (MDM2), and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) expression with its aberrations. Observations This study shows that MCL constituted 4.2% (21/500) of all NHLs with a mean age of 57.5 years (median 60 years, range 30 to 80 years). The disease was nodal in 19, and extranodal in the remaining two cases. 14 of 21 (67%) had generalized lymphadenopathy and 71% had bone marrow (BM) involvement. The nodal involvement was diffuse in 9/17 (53%), 8/21 (38%) had a blastoid morphology, and an in-situ MCL pattern was not seen in any of the cases selected for the study. Cyclin D1 immunoexpression correlated well with SOX11; CD5-negative in five cases; and CD23-positive in three cases. TP53 and c-MYC expression were noted in 17/19 (89.4%) and 8/17 (47%), respectively. MUM1 registered positive in six cases. None of the cases showed immunopositivity for MDM2 and EBV-LMP1. Conclusion In essence, this study indicates that morphological and immunophenotypic subclassification of mantle cell lymphoma with a wider panel of IHC markers is essential for understanding disease biology and better prognostication.

Bone marrow trephine immunohistochemistry is useful in characterizing malignancy-associated myelonecrosis: A retrospective observational study.

OBJECTIVE: We aim to describe the utility of immunohistochemistry (IHC) in characterizing malignancy-associated myelonecrosis (MN) on bone marrow trephine biopsies (BMBx) as a part of initial workup. MATERIALS AND METHODS: Patten and intensity of antigenic immunoexpression in necrotic tumor cells on BMBx were evaluated in a series of cases using standardized avidin-biotin-complex immunoperoxidase technique after heat-induced epitope retrieval and compared the same with viable tumor cells wherever available. RESULTS: Fifteen out of 2494 (0.6%) cases (median age: 28 years; range: 4 to 66 years) had evidence of MN (extensive in eight, moderate in five, and focal in two) secondary to hematological (N = 9) and solid (N = 6) malignancies. Five (33.3%) had pancytopenia, and eight (53.3%) had difficult and/or hemodiluted aspirate. Antigenic expression for CD10, CD79a, CD3, CD7, and CD20 was retained by necrotic leukemic blasts or lymphoma cells; CD34, TdT, and PAX5 showed heterogeneous expression; and a weak Golgi zone (dot like) CD30 positivity was noted in Reed-Sternberg (RS) or RS-like giant cells. Necrotic epithelial metastases retained pancytokeratin in all and showed variable positivity for prostate-specific antigen, carcinoembryonic antigen, CK20, ER, PR, and GATA3. Necrotic neuroblastomas (N = 2) retained positivity for synaptophysin and chromogranin, whereas retained nuclear positivity for NKX2.2 in necrotic Ewing family of tumor (N = 1) aided in early diagnosis. CONCLUSION: Myelonecrosis may retain tumor antigenicity, and immunohistochemistry using selected panel of antibodies should be tried in such challenging cases for an early presumptive diagnosis and further decision making.

Ergotamine Induced Retroperitoneal Fibrosis.

Retroperitoneal fibrosis (RPF) is an uncommon disease characterised by the presence of fibroinflammatory reaction which starts around the infrarenal portion of the abdominal aorta in the retroperitoneum and frequently entrap the ureter causing obstructive uropathy. Approximately, two thirds of the cases are idiopathic, where aetiopathogenesis is not known. Ergotamine-induced RPF, although rare, is considered under secondary group. The fibrogenic process here is thought to be due to serotonergic activity. We report a case of RPF in a young female with obstructive uropathy who had history of long-term ergotamine intake for migraine. Histopathological evaluation revealed different evolving stages of necrotising vasculitis. In addition, the patient has responded to withdrawal of offending drug along with immunosuppressive therapy. We believe, apart from serotonergic activity, ergotamine can lead to RPF through a vasculitic process which has not been reported earlier.