Prompt Cytopathological Diagnosis of Multiple Xanthomatous Skin Nodules in an Adolescent Girl Opening the Doors to Detection of Familial Hypercholesterolemia.

BACKGROUND: Xanthomas are papulo-nodular, yellow, soft, painless, dermal-based non-neoplastic cutaneous lesions that comprise of localized aggregates of lipid-laden histiocytes. CASE REPORT: A thirteen-year-old adolescent girl presented with multiple, large, bilateral, nodules present over elbows, posterior aspect of heel, and knees for five years. Fine needle aspiration cytology was performed, and the smears showed numerous foamy histiocytes, a few benign spindle cells, and foreign-body giant cells against a lipidaceous background. Her maternal aunt and grandmother also had xanthelasma palpebrarum. Serum lipid levels were advised and were markedly deranged in all three of them. Based on the corroborative clinical, biochemical, and cytopathological findings, a final diagnosis of familial hypercholesterolemia (FH) was rendered. CONCLUSION: The present case sheds light on the importance of prompt cytopathological diagnosis of xanthomatous lesions, especially in children and adolescents, as it can help prevent morbidity and mortality due to associated premature adverse cardiovascular and cerebrovascular events if left undiagnosed.

Clinical and histopathological spectrum of congenital pulmonary airway malformations: A case series.

BACKGROUND: Congenital pulmonary airway malformations (CPAM) are a spectrum of cystic and non-cystic anomalies arising from abnormal airway development in utero, with an incidence of 1 in 25,000 to 35,000 births. CPAM can present prenatally or postnatally with respiratory distress, recurrent infections, or occasionally as an incidental finding. This case series aims to highlight the clinical, radiological, and histopathological characteristics of CPAM through three pediatric cases, which include types 1, 2, and 3 CPAM. CASE PRESENTATION: Case 1: A four-month-old male presented with cough, cold, and respiratory distress. Imaging revealed hypoattenuation and overinflation of the left upper lobe with mediastinal shift. Left upper lobectomy confirmed CPAM type 2. Case 2: A one-month-old female presented with recurrent respiratory distress and infections. Imaging showed a large cystic lesion in the right middle lobe. Right middle lobectomy confirmed CPAM type 3. Case 3: A two-month-old male presented with dyspnea. Imaging showed a large bullae in the right chest with mediastinal shift. Right upper lobectomy confirmed CPAM type 1. CLINICAL DISCUSSION: CPAM is a rare congenital lung malformation characterized by abnormal bronchial development and localized glandular overgrowth. Management involves surgical resection, with the timing of surgery dependent on symptomatology. Early identification and intervention are crucial for preventing complications such as pulmonary hypoplasia and recurrent infections. Histopathological examination post-resection is essential for accurate classification and management of CPAM. CONCLUSION: This case series provides valuable insights into the clinical, radiological, and histopathological features of CPAM, including the types encountered in each case. It underscores the importance of early diagnosis and timely surgical intervention, advocating for routine prenatal and postnatal screenings to effectively identify and manage CPAM.

Bilateral primary ovarian Ewing sarcoma recurring as left submandibular lymphadenopathy diagnosed on cytology.

Ewing sarcoma (ES) is a highly malignant and aggressive small round-cell tumor originating from primitive neuroepithelium and mesenchymal stem cells. It is usually seen in children and adolescents with a male predilection and a preponderance to occur in long bones. Although skeletal/soft tissue ES is encountered in clinical practice, primary ES of the genital tract, particularly bilateral primary ovarian ES, is highly uncommon, with only a handful of cases reported worldwide. Ovarian ES is occasionally reported to involve para-aortic and pelvic lymph nodes in advanced stages. Still, cervical lymph node metastasis from ovarian ES is an infrequent clinical occurrence and, when present, indicates a worse prognosis. Here, we present an intriguing case of bilateral peripheral primary ovarian ES in an adult female, recurring as metastasis in the left submandibular lymph node. This case underlines the importance of keeping metastasis from ES as a possible differential while diagnosing metastatic small round cell tumors in peripheral lymph nodes. It also highlights the usefulness of a minimally invasive diagnostic modality of fine needle aspiration cytology and cell block preparation with applied ancillary techniques of immunohistochemistry and confirmatory molecular testing by fluorescence in-situ hybridization (FISH), for an accurate and quick diagnosis of such entities. The cytological diagnosis of our patient helped in the prompt and early initiation of chemotherapy without requiring any invasive procedure.

Utility of anticoagulation, pre-smearing and post-smearing hemolytic techniques on morphological assessment and reproducibility in fluid cytology.

Objective: Knowledge of proper collection, storage, preservation, and processing techniques is critical to ensuring proper handling and analysis of fluid cytology specimens. This study was conducted to determine the effect of anticoagulation, pre-smearing acetic acid treatment technique, and saline rehydration technique on morphological assessment, reproducibility, and reporting in fluid cytology. Material and Methods: The study was carried out in the cytopathology laboratory over 2 months (April-May 2022), where 100 effusion samples were analyzed. At least 20-40 mL of fluid was collected in heparinized and non-heparinized containers for each patient. Samples were processed in cytospin and stained with Giemsa and Papanicolaou stains. For 70 hemorrhagic specimens, an extra smear was prepared from the sediment and subjected to the saline rehydration technique as per the Indian Academy of Cytologists (IAC) guidelines. Seventy-three hemorrhagic specimens whose quantity received was more than 35 mL were subjected to the pre-smearing technique. These smears were evaluated for (a) the presence or absence of blue background/any other background staining, (b) cellularity, (c) cell morphology and (d) the presence/absence of microclots. Results: Heparinized samples showed no compromise in cellular morphology or cellularity although a blue background was observed in an occasional case. The pre-smearing technique had less background hemorrhage and preserved cell characteristics. The post-smearing saline rehydration technique did not compromise the cellularity but distorted morphology and showed background staining. Conclusion: The pre-smearing acetic acid treatment showed better-preserved cellularity and cytomorphology with the absence of background staining when compared to the post-smearing saline rehydration technique.

Bilateral primary ovarian Ewing sarcoma recurring as left submandibular lymphadenopathy diagnosed on cytology

ABSTRACT Ewing sarcoma (ES) is a highly malignant and aggressive small round-cell tumor originating from primitive neuroepithelium and mesenchymal stem cells. It is usually seen in children and adolescents with a male predilection and a preponderance to occur in long bones. Although skeletal/soft tissue ES is encountered in clinical practice, primary ES of the genital tract, particularly bilateral primary ovarian ES, is highly uncommon, with only a handful of cases reported worldwide. Ovarian ES is occasionally reported to involve para-aortic and pelvic lymph nodes in advanced stages. Still, cervical lymph node metastasis from ovarian ES is an infrequent clinical occurrence and, when present, indicates a worse prognosis. Here, we present an intriguing case of bilateral peripheral primary ovarian ES in an adult female, recurring as metastasis in the left submandibular lymph node. This case underlines the importance of keeping metastasis from ES as a possible differential while diagnosing metastatic small round cell tumors in peripheral lymph nodes. It also highlights the usefulness of a minimally invasive diagnostic modality of fine needle aspiration cytology and cell block preparation with applied ancillary techniques of immunohistochemistry and confirmatory molecular testing by fluorescence in-situ hybridization (FISH), for an accurate and quick diagnosis of such entities. The cytological diagnosis of our patient helped in the prompt and early initiation of chemotherapy without requiring any invasive procedure.

Cytomorphology of skin adnexal tumors and its correlation with histopathology in a tertiary care center.

Objectives: Even though fine-needle aspiration cytology (FNAC) can be successfully used for describing the cytomorphology of skin adnexal tumors and can help in identification of them as benign or malignant, histopathology remains the gold standard in confirmation of diagnosis. Skin adnexal tumors are a large and diverse group and are relatively less commonly encountered in routine practice; hence, knowledge of cytological features of these lesions is crucial for their appropriate management. The present study aims to evaluate the cytomorphological features of skin adnexal tumors on FNAC smears and their correlation with the histopathology. Material and Methods: This is a retrospective study of FNAC of 60 cases of subcutaneous and dermal swellings over a period of 4 years from August 2018 to August 2022 in a tertiary care center. Results: In the 60 cases of skin adnexal tumors evaluated, most cases were within the 2nd to 4th decade with male predominance. The FNA smears were helpful in picking up the nature of skin adnexal tumors, as in our case series, malignant lesions were 8.3% and benign were 91.7%. Majority adnexal lesions were of follicular or sebaceous differentiation. Histological diagnosis was available in 38 cases. Cytological diagnosis in 34 cases was concordant with histopathology. There was discrepancy observed in two cases which were reported as benign skin adnexal tumor but later turned out to be sebaceous carcinoma on histopathology. Conclusion: Even though histopathology being the gold standard for confirmation of diagnosis, in the current era of minimally invasive procedures, FNAC stands out as a valuable modality and can be a promising alternative to diagnose skin adnexal tumors and understand their cytomorphology as the data are limited about it.

Thymoma diagnosis and categorization in the current scenario: Morphological analysis based on interobserver variability.

BACKGROUND: Thymomas are not so common tumors that are encountered in day-to-day pathology reporting. The WHO system was proposed in 2015. Although, through its detailed reporting, the WHO elaborates all subtypes and morphological clinches to diagnosis, it was important to ascertain its reproducibility in our day-to-day reporting. AIMS: The aims of the study were (1) to study the interobserver agreement, concordance rates, and variability in the classification of a large number of thymomas received in our department as per the WHO 2015, (2) to correlate the WHO subtype with Masaoka-Koga stage, and (3) to study the variations in demography of thymomas in Indian patients as compared to those reported in the literature. SETTING AND DESIGN: This retrospective study was done at a tertiary care teaching hospital with huge surgical oncology patient load, also pertaining to the cardiothoracic surgeries. It is predominantly an interobserver agreement design to study the reproducibility of the WHO 2015 classification on thymic epithelial tumors. METHODS: Four pathologists have independently reviewed histopathology slides of 65 cases of thymomas and classified them into predefined categories. Kappa statistics was applied to the observations. RESULTS: There was a substantial interobserver agreement in overall classification of thymomas with a Cohen's kappa score of 0.66. A better score was achieved for the classification of Group B thymomas. The WHO subtypes correlate well with the Masaoka-Koga staging system, and this finding is statistically significant. This article also presents the clinical details of a large number of thymoma cases. CONCLUSION: The new WHO classification has good reproducibility among pathologists in thymoma reporting.

Mucoepidermoid Carcinoma in Carcinosarcoma of the Lung - A Rare Combination.

Carcinosarcomas of the lung are uncommon neoplasms and are presently categorized along with sarcomatoid carcinomas in the WHO 2004 classification. Morphological recognition of individual components in a surgical specimen is usually straightforward. The respiratory epithelium is also a rare site for salivary gland type tumors. A 72-year-old lady who was investigated for an episode of hemoptysis was found to have a well circumscribed intraluminal tumor. The histo-morphological features were unique and composed of mucoepidermoid carcinoma and undifferentiated sarcoma. To the best of our knowledge, this unusual morphological combination has never been reported in literature.

Sclerosing Angiomatoid Nodular Transformation of the Spleen: A New Entity or a New Name?

Sclerosing angiomatoid nodular transformation of the splenic red pulp has been described quite recently; many of the lesions previously diagnosed as splenic exuberant granulation tissue, multinodular hemangioma, and inflammatory pseudotumor could actually belong to this category. The lesion has been well reported intermittently in the past, but new cases with still newer associations keep appearing from time to time. There are no known risk factors and no inciting triggers have been proven. We report two such cases- one of which has extensive extramedullary haematopoiesis; a feature that has never been reported earlier. Clinico-morphological and radiological features along with pathogenesis are discussed in detail.

Extensive osteolytic skull base amyloidoma simulating malignancy: A rare pseudotumor producing a diagnostic dilemma.

Although amyloidomas are quite well-known, intracranial, and especially skull base lesions have been rarely reported. Extensive lesions in the skull base frequently simulate malignancy clinicoradiologically. Diagnosis of these lesions is important as they offer a favorable prognosis. We describe a large infiltrating osteolytic skull base tumor-like lesion in a 45-year-old male without evidence of associated plasma cell dyscrasia. Squash smears and histopathology revealed a plasma cell-rich lesion with abundant amyloid, confirming amyloidoma. To conclude, amyloidoma of the skull base is a rare tumor-like lesion, with timely diagnosis and management offering a good prognosis.

Aspergillus colonization in hydatid cyst: Addition of a case.

Aspergillus is a common saprophytic fungus that causes invasive or non-invasive disease in humans. It commonly colonizes pre-existing lung cavities. It has been earlier reported to coexist in previously operated or ruptured hydatid cysts. However there have been only few case reports of its occurrence in previously unoperated cysts in immunocompetent hosts. The present case adds to this category.

A forgotten disease reminds itself with a rare complication.

Diagnosed cases of sexually transmitted diseases (STD) represent tip of the iceberg and Donovanosis in one of them. Donovanosis, in most cases is obvious clinically, but rely for its confirmation on the demonstration of donovan bodies in histological sections and cytological preparation. In an extremely rare setting, this disease may get complicated by the development of squamous cell carcinoma. We report this occurrence in an 18-year-old girl to review the currently forgotten status of donovanosis amongst the STDs and the poor outcome of the disease if left untreated.

Experimental therapeutics for patients with myeloproliferative neoplasias.

Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) are characterized by stem cell-derived, unrestrained clonal myeloproliferation. The World Health Organization classification system, proposed in 2008, identifies 7 distinct categories of Ph-negative MPNs including essential thrombocythemia (ET); polycythemia vera (PV); primary myelofibrosis (PMF); mastocytosis; chronic eosinophilic leukemia; chronic neutrophilic leukemia; and MPN, unclassifiable. For many years, the treatment of ET, PV, and PMF, the most frequently diagnosed Ph-negative MPNs, has been largely supportive. In recent years, that paradigm has been challenged because of the discovery of a recurrent point mutation in the Janus kinase 2 (JAK2) gene (JAK2(V617F)). This mutation can be detected in the vast majority of patients with PV and approximately half of patients with ET or PMF and serves as both a diagnostic marker as well as representing a putative molecular target for drug development. Several putative targeted agents with significant in vitro JAK2 inhibitory activity and various degrees of JAK2 specificity are currently undergoing clinical evaluation. Furthermore, other investigational non-tyrosine kinase inhibitor approaches such as immunomodulatory agents and pegylated interferon- have also shown promising results in MPNs.

Teratomas in central nervous system: a clinico-morphological study with review of literature.

BACKGROUND: Cranio-spinal axis teratomas are rare. This subset is interesting because symptoms can be varied, depending on the location. Histopathology is diagnostic; most of the lesions are benign. Rarely, malignancy develops in any of the somatic components. AIMS: To study the demographic, clinico-morphological and follow-up data of central nervous system (CNS) teratomas. MATERIALS AND METHODS: Cases diagnosed as mature or immature teratomas in the CNS over a 20-year period were included in the study. Clinico-radiological, demographic and follow-up data of these cases were analyzed. RESULTS: A total of 14 tumors were diagnosed as teratomas. Of these, 11 were mature cystic teratomas; and 1 case each, of teratoma with malignant transformation, terato-carcinoma and mixed germ cell tumor (immature teratoma with germinoma). Six of the 14 cases were intracranial and 8 were spinal. Presenting features varied according to the location. Radiologically, contrast enhancement with predominantly solid component was suggestive of malignancy or an aggressive tumor. Morphologically, a variety of tissue derivatives were seen in the cases. Excision was curative or provided symptomatic relief in most cases; terato-carcinoma and mixed germ cell tumor patients needed adjuvant radiotherapy. CONCLUSION: CNS teratomas are rare. Morphology and location decide outcome.

Chronic myeloid leukemia in the tyrosine kinase inhibitor era: what is the "best" therapy?

The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-alpha and vaccines. This review highlights progress made in the treatment of CML in the past year.

Tyrosine kinase inhibitors: the first decade.

The treatment of chronic myeloid leukemia (CML) drastically changed with the introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), in 1998. By directly targeting this leukemogenic protein kinase, imatinib affords patients with CML sustained chromosomal remissions, which translate into prolonged survival. However, there has been concern over the emergence of resistance to imatinib, and some patients fail to respond or are intolerant of imatinib therapy because of untoward toxicity. This has spurred interest in developing novel TKIs to overcome the mechanisms of resistance that lead to treatment failure-most importantly, Bcr-Abl1 kinase domain mutations. Two of these second-generation TKIs, nilotinib and dasatinib, are approved worldwide for the treatment of CML after imatinib failure or intolerance. Although these agents are active, they fail in many patients because of the development of highly resistant mutations such as the T315I, against which several novel agents are currently being tested in clinical trials. This review provides an account of the progress made in the field of TKI therapy for CML over the past decade.