Role of C-Reactive Protein and Erythrocyte Sedimentation Rate in the Diagnosis and Monitoring of Treatment Response in Treatment Naïve Subjects with Chronic Pulmonary Aspergillosis.

PURPOSE: The role of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) for diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Herein, we investigate the diagnostic performance of serum ESR and CRP in CPA. METHODS: We retrospectively analyzed the data of treatment-naïve subjects with CPA and diseased controls (post-tuberculosis lung disease on CT thorax). We treated CPA subjects with six months of oral itraconazole. Our primary objective was to evaluate the sensitivity and specificity of ESR and CRP in diagnosing CPA. The key secondary objective was to study the change in the inflammatory markers with treatment. RESULTS: We included 434 subjects and 20 diseased controls. The sensitivity and specificity of ESR (n = 434) and CRP (at cut-off value of 10 mg/L, n = 308) in diagnosing CPA were 42.9% and 65%, and 52.3% and 65%, respectively. Both ESR and CRP had erratic trend following treatment. ESR and CRP declined or remained stable in approximately 60% of subjects but increased in approximately 40% of the subjects despite treatment. CONCLUSION: Serum CRP and ESR have limited utility in diagnosing and following subjects with CPA.

An Autopsy Case of Wiskott-Aldrich Syndrome Revealing "FDC-Only Lymphoid Follicles" in Lymphoid Tissue: A Morphologic Correlate of Defective Immune Synapse.

Wiskott-Aldrich Syndrome (WAS) is an inherited disorder characterized by the classical triad of eczema, micro-thrombocytopenia, and immune deficiency. This disease affects the hematopoietic cells to a variable extent. The spectrum of clinical and laboratory data for WAS has been well described in the literature though there is a paucity of its histopathologic and immunohistochemical correlates. The current case describes the autopsy findings of this rare entity in an 8-year old male child with specific recognition of altered histology noticed in the lymphoreticular tissues. The predominant morphological finding in lymphoid tissue was atretic hyalinized germinal centers labeled as "the follicular dendritic cell (FDC)-only lymphoid follicles." Immunohistochemistry revealed a reduction in germinal-center B-cells, T-follicular helper cells, attenuated mantle zone, FDC proliferation, and paracortical plasmacytosis. This case highlights the crippled immune cell population in WAS, ultimately leading to the morphology of atretic follicles rich in FDCs.

Metastatic germ cell tumour in effusion cytology.

BACKGROUND: Germ cell tumours infrequently metastasise to body cavities, where early detection on fluid samples is possible and can spearhead early treatment and survival. MATERIALS AND METHODS: A total of seven cases of metastatic germ cell tumours were retrieved out of 7500 effusion samples received for cytopathological examination from 2015 to 2021. Detailed cytological features of metastatic germ cell tumours in effusion samples were studied, along with a correlation between clinical, radiological, and histopathological features. RESULTS: A total of seven cases of metastatic germ cell tumours were analysed in effusion samples which included dysgerminoma (2), immature teratoma (2), yolk sac tumour (1), embryonal carcinoma (1), and mixed germ cell tumour (1). The smears showed predominantly discrete or loose clusters of cells. The cells with round nuclei and prominent nucleoli were helpful in detecting dysgerminoma and yolk sac tumours. Immature teratoma showed tiny groups of small cells and mature squamous cells. Serum tumour markers were raised in the majority of cases. CONCLUSION: Metastatic germ cell tumours in effusion are uncommon, but detailed clinical history, including serum markers and characteristic cytological features, are helpful in their diagnosis.

An Autopsy Case of ß-Thalassemia Major Illuminating the Pathological Spectrum of the Disease.

Despite declining rates worldwide, autopsy studies remain invaluable tools to expand existing knowledge on the pathophysiology of diseases, especially those with multisystem involvement. ß-thalassemia major (ß-TM) is a relatively common hemoglobinopathy in India and is characterized by a regular requirement for life-sustaining transfusions and chelation. The iron overload is an invariable side effect. This secondary hemosiderosis leads to several complications, primarily in the heart, liver, pancreas, and endocrine organs. Despite adequate transfusion and chelation, untransplanted patients may show early mortality for several reasons. We report a 10-year-old boy with ß-TM who died with clinical possibilities of iron overload-related cardiac failure and pulmonary arterial hypertension. His autopsy revealed certain unique disease pathologies in the form of minimal cardiac fibrosis in the presence of significant cardiac siderosis and widespread endocrine damage due to iron-overload. A null-cell pituitary microadenoma, previously undescribed in thalassemia syndromes, was found. This report highlights the importance of the diminishing art of autopsy, without which these histopathological insights would not have emerged.

Antenatally Detected Multiple Mediastinal Enterogenous Cysts in a Newborn Presenting with Severe Cardio-Respiratory Compromise and Early Life-Saving Management.

Posterior mediastinal enterogenous cyst is a rare entity in neonate. The neonate can present with severe cardio-respiratory compromise in the form of respiratory distress, shock, cardiac failure or arrhythmia soon after birth which may require immediate surgical intervention. Antenatal screening can demonstrate the cystic mass in fetus early and can help in quick postnatal management. Multidisciplinary management with aspiration of the cysts was life-saving in the present case.

Primary seminal vesicle adenocarcinoma: A case report of rare entity and discussion of its differential diagnosis using immunohistochemical approach for the core biopsy specimen.

Primary seminal vesicle adenocarcinoma is a rare malignancy of the male genito-urinary system with only a few confirmed reported cases. Initial tissue diagnostic modality is often a core biopsy specimen. Here, we report this rare entity in a 50-year-old male, highlighting the histomorphological and immunohistochemical approach to the core biopsy specimen of the seminal vesicle mass. The patient presented with a history of haematospermia and gross haematuria for one year, and radiological workup was found to have a right seminal vesicle mass. A trans-rectal ultrasound guided core biopsy revealed a tumourous lesion with a predominant papillary architecture and cytological features of neoplasia. Based on positivity for CK7, PAX-8 and CA-125, and Ki-67 index of 30%-40% and negativity for PSA, AMACR, CK20, CDX-2, p63, GATA3, WT1 and calretinin, a diagnosis of primary seminal vesicle adenocarcinoma was offered. The diagnosis was also confirmed on the surgically resected specimen. This case depicts the approach of a pathologist to diagnose this rare entity on the core biopsy specimen and the possible differential diagnoses one must consider.

Bridging the gap: understanding contemporary autopsies in acute leukemia by comparing ante-mortem and post-mortem profiles.

This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.

SelSA-1, a novel HDAC inhibitor demonstrates enhanced chemotherapeutic potential by redox modulation.

Colorectal cancer (CRC) is a multistep disorder resulting from genetic and epigenetic genome changes. It is the third most common malignancy in developed nations accounting for roughly 600,000 deaths annually. Persistent gut inflammation, as observed in inflammatory bowel disease (IBD), is a key risk factor for CRC development. From an epigenetic viewpoint, the pharmacological inhibition of HDACs using HDAC inhibitors such as SAHA has emerged as a suitable anticancer strategy in the recent past. However, the clinical success of these strategies is limited and has risk factors associated with their uses. Thus, considering the critical involvement of epigenetic regulation of key molecular mechanisms in carcinogenesis as well as HDAC inhibitory and anti-tumorigenic properties of Selenium (Se), we aimed to explore the potentially safer and enhanced chemotherapeutic potential of a Se derivative of SAHA namely SelSA-1, in an experimental model of colitis-associated experimental cancer (CAC) model and mechanism involved therein. The in vitro study indicated improved efficiency, specificity, and better safety margin in terms of lower IC50 value of SelSA-1 than SAHA in both NIH3T3 (9.44 and 10.87 µM) and HCT 115 (5.70 and 7.49 µM) cell lines as well on primary colonocytes (5.61 and 6.30 µM) respectively. In an in vivo experimental model, SelSA-1 efficiently demonstrated amelioration of the multiple plaque lesions (MPLs), tumor burden/incidence, and modulation of various histological and morphological parameters. Further, redox-mediated alterations in apoptotic mediators suggested induction of cancer cell apoptosis by SelSA-1. These findings indicate the enhanced chemotherapeutic and pro-resolution effects of SelSA-1 in part mediated through redox modulation of multiple epigenetic and apoptotic pathways.

Pregnancy-associated mucinous cystic neoplasms of the pancreas - A systematic review.

INTRODUCTION: Mucinous cystic neoplasms (MCN) are mucin-producing epithelial cell tumors of pancreas. They consist of an ovarian-type stroma expressing estrogen and progesterone receptors. Pregnancy-associated MCNs are presumed to be larger in size and more aggressive without any concrete evidence. OBJECTIVE: and Data Sources: Systematic review of published literature using PubMed and Google Scholar databases. Original articles including case reports and series published between 1970&2021 were included wherein MCN was diagnosed during pregnancy/within one-year post-partum. Thirty-three publications having 36 cases, adding one of our own patient were analyzed in this review. RESULT: Median age at presentation was 32 years. Only three (9%) patients were asymptomatic. Mean size of MCN was 135 mm. Ten patients (27%) reported an increase in size during pregnancy. Most tumors involved body and tail of pancreas (60%). Distal pancreatectomy with splenectomy was the most common resection performed (57%). No foetal mortality was reported to date. CONCLUSION: Pregnancy may cause a rapid increase in size of MCN. Decision-making is more complex and needs a fine balance between optimal oncological and obstetric outcomes.

Cytomorphological characterisation of angioimmunoblastic T cell lymphoma: a case-control study.

AIMS: Angioimmunoblastic T cell lymphoma (AITL) is often misdiagnosed in cytology. Hence, the present study was conducted to identify the distinctive cytomorphological features of AITL in lymph node fine-needle aspirates (LN-FNA). METHODS: This was a 4-year retrospective case-control study. Cases included LN-FNAs from patients with histopathologically confirmed AITL. The controls included LN-FNAs from patients with histopathologically confirmed reactive lymphoid hyperplasia (RLH; n=25). Eleven cytomorphological features were assessed in all the aspirates; the strength of association was determined by OR, Cramer's V and multiple correspondence analysis (MCA). RESULTS: Of a total of 22 cases of AITL reported on histopathology, 19 adequate aspirates from 14 patients (63.6%) were available for review. On univariate analysis, 5 of 11 cytomorphological variables were found to be significant for AITL; however, on MCA, 3 of these parameters, viz absence of tingible body macrophages (OR=0.014; V=0.74), presence of atypical lymphoid cells (OR=10.8; V=0.41) and singly scattered epithelioid cells (OR=19.3; V=0.31), were found to be the strongest predictors of AITL. CONCLUSIONS: The absence of tingible body macrophages, presence of atypical lymphoid cells and singly scattered epithelioid cells in polymorphic LN-FNAs are significant cytomorphological predictors of AITL in comparison with RLH. Knowledge of these diagnostic predictors, supplemented by clinicoradiological correlation and appropriate ancillary studies, can help diagnose AITL on aspiration cytology.

Bone Marrow Metastasis in a Suspected Case of Angiosarcoma Unravelled by Immunohistochemistry.

A 40-year-old female presented with progressive fatigue and left upper abdominal discomfort for 1 month. CT scan revealed ill-defined hypervascular lesions in the liver and diffuse enlargement of the spleen. She had severe anemia with leukoerythroblastic reaction. Bone marrow smears revealed clusters and discrete spindle cells, few plump and round cells. Trephine biopsy revealed an infiltrative spindle-cell neoplasm replacing the marrow with the focal presence of epithelioid cell clusters. On immunostaining, the tumor cells were positive for CD34, CD31, Friend Leukemia Virus Integration-1 (FLI1), and vimentin, consistent with metastatic angiosarcoma. There were multiple small aggregates of 5-10 MIB-1 positive tumor cells (overall positivity < 1%). She succumbed to her illness before initiation of any therapy. Bone marrow metastasis of angiosarcoma is extremely rare. The aggressive clinical course and judicious use of immunohistochemical markers are required for definitive diagnosis.

Waldenström Macroglobulinemia of the orbit: A diagnostic challenge.

PURPOSE: Ocular adnexal lymphomas (OAL) constitute 55% of all orbital tumors. Waldenström Macroglobulinemia (WM) presenting as an orbital mass with diffuse extraocular muscle (EOM) involvement is rare. We report an elderly patient who presented to the ophthalmologist for an orbital mass which on evaluation, turned out to an ocular adnexal WM. OBSERVATIONS: A 75 years old man presented with a palpable mass in the left anterior superior orbit and bilateral restricted ocular motility in all gazes. Computed tomography scan revealed a hyperdense mass with diffuse thickening of extraocular muscles and enlarged lacrimal gland on the left side. Incisional biopsy of the mass revealed a lymphoproliferative neoplasm with plasmacytic morphology. Immunohistochemistry (IHC) of the orbital mass as well as the bone marrow was sought, lymphoplasmacytic lymphoma (CD20+, CD38+, MUM1+, BCL 2+, CD3-, CD5-, CD10-, CD23-, cyclin D1). Bone marrow flow cytometry showed CD5-, CD10- kappa restricted B cell neoplasm. Serum analysis significantly elevated IgM levels. This indicated a diagnosis of ocular adnexal Waldenström Macroglobulinemia. CONCLUSION AND IMPORTANCE: This case highlights the importance of clinical evaluation, histopathology, and immunohistochemistry for phenotyping of ocular adnexal lymphomas.

Thyroid eye disease with concurrent orbital lymphoma: a radiological surprise.

Summary: Thyroid eye disease (TED) is the most common extra-thyroidal manifestation in Graves' disease (GD). Additional/concurrent/synchronous pathologies may be present, especially in elderly patients who present with atypical features such as non-axial (or eccentric) proptosis, absence of lid lag and restricted superior extra-ocular movements. A 70-year-old female presented with progressive proptosis of her left eye and diplopia. She was diagnosed with GD a year prior and initiated on carbimazole. On examination, she had eccentric proptosis, restricted superior extra-ocular movements and a palpable mass in the supero-temporal quadrant of the left eye. Her T3 (1.33 ng/mL) and T4 (8.85 µg/dL) were normal with carbimazole. Thyroid-stimulating hormone (TSH)-receptor antibody was positive (3.15 IU/L, reference range <1.75). MRI revealed an enhancing lesion infiltrating the left superior rectus, with concurrent characteristic muscle belly involvement bilaterally. Orbital biopsy showed atypical lymphoid cells (CD20+), suggesting marginal zone lymphoma. CT thorax and abdomen, fluorodeoxyglucose-positron emission tomography and bone marrow examination were normal. The patient was administered orbital radiotherapy for her localised lymphoma and carbimazole was continued. TED is the most common cause of orbital involvement overall and in GD. However, additional or alternative pathology may be present which requires evaluation. MRI can be a useful adjunct in these patients. Orbital lymphoma needs to be staged with workup for disseminated disease. Radiotherapy is the treatment of choice for localized disease. The index case provides evidence for synchronous presentation of dual pathology and highlights the importance of astute clinical examination as well as keeps a low threshold for MRI in selected cases. Learning points: Thyroid eye disease can co-exist with other ocular pathology, especially in elderly individuals. Eccentric proptosis, absent lid lag and restriction of eye movements (suggesting tendon involvement) should alert towards the presence of alternative pathology. Orbital imaging using MRI not only has greater sensitivity in diagnosing radiologically bilateral disease in patients who have unilateral involvement clinically but is also useful to identify concurrent neoplasms.

Adrenal pheochromocytoma with involvement of aorta and left renal artery: salvaged with adrenalectomy and nephrectomy.

Large adrenal pheochromocytomas encasing the renal artery are a rare entity. The management of such challenging cases is surgical resection. The involvement of renal tissue and renal artery may necessitate meticulous dissection and concomitant nephrectomy. Here, we present a case of 41-year-old man diagnosed with left adrenal pheochromocytoma with complete encasement of left renal artery and partial encasement of aorta. Open left adrenalectomy and nephrectomy was performed after adequate preoperative optimisation. The patient is doing well at 6-month follow-up. Large adrenal pheochromocytoma with renal involvement is a rare presentation and requires optimal preoperative imaging, adequate preoperative alpha and beta blockade and meticulous surgical technique.

Pulmonary histopathology in fatal paraquat poisoning.

Paraquat is a potent herbicide widely used in the Indian agriculture industry. Human fatality due to paraquat poisoning is not uncommon in this country. The primary effect of paraquat is on the lungs, and the resultant pulmonary damage leads to the patient's demise. There is a high mortality rate in paraquat poisoning as the treatment is usually supportive with no known antidote. There are limited human studies that have observed the histopathological changes in lungs in paraquat poisoning. The authors have discussed the time-related histopathological changes in lungs in paraquat poisoning on autopsy subjects. The role of anticoagulants and fibrinolytic agents in the treatment of this poisoning has also been discussed.