Histopathological Evaluation of Angiogenic Markers in Non-Hodgkin's Lymphoma.

Background Angiogenesis plays a key role in the development, maintenance, and progression of tumor. The incidence of non-Hodgkin's lymphoma (NHL) is increasing from the past three decades. Materials and Methods The aim of the study is to evaluate microvessel density (MVD) using CD34 monoclonal antibody and vascular endothelial growth factor (VEGF) using monoclonal antibody that were studied in pretreatment paraffin-embedded tissue samples of 60 cases. Results MVD was found to be increased in parallel with increasing grade of tumor. B-NHL had a mean MVD of 79.5 ± 8.8 (no./mm 2 ), while T-NHL had a mean MVD of 183 ± 37.6 (no./mm 2 ). VEGF expression was seen in 42 cases (70%), 20 cases (33.3%) showed strong VEGF expression, and the remainder showed either weak (36.6%) or no (30%) staining. Strong VEGF expression is seen in 100% cases of T-NHL and 77.7% cases of B-NHL. Mean MVD and VEGF expression was found to be correlated significantly with the histological grade of NHL ( p = 0.001 and p = 0.000, respectively). Average microvessel counts were 53, 82.9, and 130.8 vessels (no./mm 2 ) for negative, weak, and strong VEGF staining, respectively. These differences were statistically significant ( p = 0.005 for strong vs. negative and p = 0.091 for strong vs. weak VEGF staining individually). Conclusion As the grade of tumor progresses, the angiogenic potential also advances which seems to depend on VEGF. The presence of higher MVD in high-grade lymphomas can be utilized for antiangiogenic drugs.

Role of Intraoperative Pathology Consultation by Imprint and Scrape Cytology in Soft Tissue Tumors and Tumor-Like Lesions.

Intraoperative pathologic consultation plays an essential role in therapeutic decision making, possibly avoiding under or overtreatment of the patient. Common indications for intraoperative consultation include obtaining a diagnosis in an unknown pathology, ruling out malignancy, confirming a provisional diagnosis, and assessing margin status. Fifty patients undergoing surgery for soft tissue tumors or tumor-like lesions were included in the present prospective study to evaluate the role of intraoperative pathologic consultation by imprint and scrape cytology. Careful and quick gross examination of the specimen was performed, followed by processing for imprint and scrape smears. The prepared smears were evaluated by three pathologists and the cytological diagnosis compared subsequently with final histopathological diagnosis. Intraoperative consultation was primarily requested to make or confirm preoperative diagnosis. In 44.0% cases, no previous tissue/cytological diagnosis was available. In 56.0% cases, previous pathological diagnosis was available, but the reports were inconclusive or were reported from outside our institute. The diagnostic yield of imprint smears was 24% (5 malignant, 6 benign, and 1 inconclusive), and scrape smears was 100% (10 malignant, 38 benign, and 2 inconclusive). Paraffin-embedded sections yielded diagnosis in 100% cases (11 malignant, 38 benign, and 1 nonneoplastic). Imprint smears alone were not of much help in intraoperative diagnosis. Scrape smears were found to be superior to imprint smears in terms of diagnostic yield and accuracy. Combined imprint and scrape smear cytology did not provide any advantage in intraoperative provisional tissue diagnosis in soft tissue tumors.

Evaluation of DNA ploidy and S-phase fraction in fine needle aspirates from breast carcinoma.

BACKGROUND: The use of fine-needle aspiration (FNA) as a primary tool in the diagnosis of breast carcinoma provides opportunity for early proliferative characterization of the tumor. This study was undertaken to assess DNA ploidy and S-phase (SPF) fraction by flow cytometry in fine needle aspirates of patients with breast cancer. METHOD: Fifty patients of breast cancer diagnosed on fine needle aspiration cytology (FNAC) and who subsequently underwent either mastectomy or lumpectomy were included. Material obtained by FNAC was subjected to DNA ploidy and SPF analysis. Immunohistochemical estimation of Ki-67 was done on histopathology sections. The proliferation markers (SPF and Ki-67) were compared with each other and with the histopathologic parameters. RESULTS: On DNA flow cytometry, 27 (54%) cases were aneuploid and 23 (46%) cases were diploid. The median SPF was 12.43% and 4.03% in aneuploid and diploid tumors respectively. Median Ki-67 among aneuploid tumors was 28.6% compared to 8.7% among diploid tumors. Aneuploid tumors were significantly associated with higher values of SPF and Ki-67, with Kappa 0.437 and agreement of 72%. Diploid tumors showed lower values of SPF and Ki-67, with Kappa 0.455 and agreement of 72.7%. Correlation among SPF and Ki-67 was highly significant with Kappa value 0.446, P value of .002 and agreement of 72.3%. CONCLUSION: DNA ploidy and proliferative activity by flow cytometric SPF estimation on fine needle aspirates from breast cancer can provide valuable prognostic and predictive information at the time of diagnosis in patients with breast cancer. This might help in selection of appropriate treatment modality.

Imprint Cytology for Intra-operative Assessment of Surgical Margins for Skeletal Tumours in COVID-19 Pandemic.

In the current COVID-19 pandemic, tremendous pressure is been exerted on the existing health infrastructure of many developing nations. Limb salvage surgeries in bone and soft tissue sarcomas cannot be delayed beyond a certain time-period and constitute an orthopaedic emergency in certain situations. Evaluation of intra-operative surgical margins forms an important step especially in cases with planned close margins or intercalary resections. Techniques such as imprint cytology can be preferred over frozen sections for evaluation of the surgical margins especially in COVID-19 positive patients. The advantages it offers such as completion of the procedure within the operation room complex, no generation of aerosols, and almost equal sensitivity and specificity when compared with frozen section method do warrant a modification of current surgical practice in the current health crisis especially in resource-constrained nations. Awareness and better communication regarding the same from the pathologist to the surgical team will go a long way in conserving resources and avoid unnecessary exposure to potentially infected aerosols.

Clinico-pathological spectrum of cutaneous sarcoidosis: an experience from a government institute in North India.

BACKGROUND AND AIMS: Sarcoidosis is a multisystem granulomatous disease of unknown etiology and cutaneous involvement is the second most frequent manifestation in systemic sarcoidosis.The aim of the present study is to evaluate the clinical and pathological spectrum of cutaneous sarcoidosis and compare the same with literature available. METHODS: The present retrospective study was conducted from January 2010-March 2015 and fifteen cases diagnosed as cutaneous sarcoidosis on biopsy were reviewed. The histological spectrum of cutaneous sarcoidosis was evaluated. RESULTS: The mean age at diagnosis was 46 years. Nine (60%) cases out of 15 were females. Most common cutaneous lesions were nodules (46.6%) followed by papules (40%). Classically, lymphocyte-poor, non-caseating epithelioid cell granulomas, was the most common histologic finding. Inclusion bodies were seen in 20% cases with occasional presence of fibrinoid necrosis (13.3%). Peri-adnexal granuloma, seen in one case, raised the possibility of tuberculoid leprosy. Foreign body was seen in one case supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive. Epidermal changes including atrophy, loss of rete pegs, acanthosis, papillomatosis, hyperkeratosis, parakeratosis and basal cell vacuolation were seen in 46.6% cases. Reticulin was positive in all the cases while special stains for acid fast bacilli and fungi were negative. CONCLUSION: The clinical presentation of cutaneous sarcoidosis may be variable. Presence of naked, reticulin-rich granulomas is the most characteristic histopathological finding. Correlation of clinical history with histologic examination is essential to exclude other granulomatous diseases including leprosy, syphilis, other infectious granulomatous diseases and foreign body reaction.

Diagnostic Utility of Endometrial Aspiration Cytology in Women with Abnormal Uterine Bleeding.

CONTEXT: Abnormal uterine bleeding (AUB) is a common problem for which women seek gynecological consultation. Endometrial aspiration cytology (EAC) has emerged as a minimally invasive and cost-effective diagnostic procedure for screening the endometrial status of these patients that can aid in diagnosis in high-burden and resource-limited settings. AIMS: The study was conducted to evaluate the utility of EAC in women with AUB, and the cytological diagnosis was compared with the histopathology. MATERIALS AND METHODS: A total of 100 patients presenting with AUB were subjected to EAC using a 4-mm Karman's cannula. Later, they also underwent endometrial dilation and curettage. The cytology smears were evaluated for architectural and cytomorphological features. The cytological diagnoses henceforth made were compared with the histopathological diagnosis to calculate sensitivity, specificity, and diagnostic accuracy of EAC. RESULTS: EAC showed a sample adequacy of 89% viz a viz 90% for histopathology. EAC showed a sensitivity of 87.5% and 100% for diagnosing benign and malignant conditions, respectively. There was a good overall agreement between cytological and histopathological diagnosis (κ = 0.585). CONCLUSIONS: EAC is an effective and minimally invasive procedure for the primary investigation of women with AUB.

Role of fine-needle aspiration cytology and core needle biopsy in diagnosing musculoskeletal neoplasms.

BACKGROUND: The management of musculoskeletal neoplasms requires an accurate diagnosis, histologic type, and degree of tumor differentiation. AIM: The present study was undertaken to compare the accuracy of fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) in the diagnosis of musculoskeletal tumors and further to compare the results with histopathological examination of surgical specimens. Grading of malignant tumors was also compared on these techniques. MATERIALS AND METHODS: This prospective study was conducted on 50 patients with musculoskeletal neoplasms. Detailed history, clinical examination, and radiological investigations were undertaken. FNAC followed by CNB were performed in each case. The tumors were categorized as benign and malignant with a definitive histotype diagnosis. For malignant neoplasms, cytologic and histologic gradings were done into three grades. The sensitivity and specificity of FNAC and CNB were compared. RESULTS: Of the 50 cases with musculoskeletal neoplasms, 32 (64%) were bone tumors and 18 (36%) were soft tissue tumors. The sensitivity of FNAC and CNB for categorizing bone tumors into benign and malignant was 94.7%. For soft tissue tumors, FNAC had a sensitivity of 90.9% and CNB had a sensitivity of 100%. The specificity of both the techniques, FNA and CNB for bone and soft tissue tumors was 100%. For malignant bone tumors, cytologic grade was concordant with CNB grade in 72.2% of the cases. Cytologic grade was concordant with the grade on CNB in 81.8% cases for malignant soft tissue neoplasms. CONCLUSION: FNAC and CNB alleviate the need for an open biopsy in diagnosing and grading musculoskeletal neoplasms, thus facilitating appropriate therapeutic intervention.

Fine-needle aspiration cytology of cutaneous granular cell tumor: Report of two cases with special emphasis on cytological differential diagnosis.

Granular cell tumors (GCTs) are uncommon neoplasms with recently postulated origin from Schwann cell or neural crest. It can appear in different parts of the body and is most commonly found in the tongue. The cutaneous presentation is not that uncommon. Fine needle aspiration cytology (FNAC) has been suggested to be the diagnostic modality of choice. It will help to differentiate benign tumors from malignant ones and to differentiate GCT from frequent misdiagnoses such as granular histiocytic reaction, xanthogranuloma, rhabdomyoma, oncocyte rich lesions, alveolar soft part sarcoma (ASPS), epithelioid sarcoma, and carcinoma. We report two cases of GCT who presented with subcutaneous swellings in the right thigh and the left lumbar region for 24 months and 18 months, respectively. In the first case, a cytodiagnosis of chronic inflammation showing histiocytes was suggested while GCT was found in the second case. Subsequent histologic examination of the first case and immunocytochemistry in the second case gave the confirmatory diagnosis of GCT.

Evaluation of brush cytology and DNA image cytometry for the detection of cancer of the oral cavity.

BACKGROUND: Cancer of the oral cavity is the sixth most common malignancy reported worldwide. This study was undertaken to evaluate the efficacy of brush cytology and the adjunctive role of DNA image cytometry (ICM) in the diagnosis of oral cancer. METHOD: Oral brush smears and biopsy were obtained from 100 consecutive patients presenting with suspicious oral lesions. DNA-ICM was performed on 96 cytology smears which had adequate cellularity. RESULTS: On cytology, 54 cases were benign, 36 were malignant, 6 were suspicious for malignancy, and 4 were inadequate due to scanty cellularity. On histopathologic examination, 49 cases were diagnosed as squamous cell carcinoma and 51 cases as benign. The sensitivity of brush cytology for the detection of cancer was 83.3% and the specificity was 95.8%. The positive and negative predictive values were 95.2% and 85.2%, respectively, with a diagnostic accuracy of 86%. Out of 96 cases analyzed by image analysis to assess DNA ploidy, 33 cases were aneuploid and 63 were diploid. The sensitivity, specificity, positive predictive value, and negative predictive value of DNA-ICM were 68.7%, 100%, 100%, and 76.1%, respectively, giving a diagnostic accuracy of 81%. The combination of cytology and DNA cytometry increased the sensitivity to 92% and specificity to 100%. CONCLUSION: The study demonstrates the usefulness of DNA-ICM as an adjunct to brush cytology to diagnose oral cancer. It reduces the false negative cases on cytology and also adds to objectivity in cytologically doubtful cases.

Intraoral and Oropharyngeal Lesions: Role of Fine Needle Aspiration Cytology in the Diagnosis.

The oral cavity is affected by a wide range of pathologic lesions, for which a morphologic diagnosis is required for proper management. Fine needle aspiration (FNA) is being increasingly used for preliminary diagnoses of such lesions. This is retrospective analysis of intraoral and oropharyngeal lesions diagnosed with FNAC over a period of 7 years. Out of total 55 cases, a definite diagnosis could be made on cytology in 50 cases (90.9 %). These 50 cases were further included in the study. Thirty cases were reported as non-neoplastic and 20 as neoplastic (11 benign and nine malignant). The diagnoses were made taking into account the background material (blood, mucin) and the predominant cells present (neutrophils, lymphoid cells, macrophages, hemosiderin laden macrophages, squamous cells, basaloid cells, spindle cells, giant cells). Histopathological diagnosis was available in 17 cases and corresponded with FNA diagnosis in 16 cases (94.12 %). No significant complications were seen in patients undergoing these FNAs. It can be concluded that FNA is a simple and rapid diagnostic test that can be useful for preliminary assessment of oral and oropharyngeal lesions.

Cytological diagnosis of small cell osteosarcoma of the bone.

Small cell osteosarcoma (OS) is a rare histological variant of OS that poses unique diagnostic difficulties. We present a case of a 10-year-old child who underwent fine needle aspiration cytology (FNAC) from a mass in the right thigh. The cytological findings were those of a malignant small round cell tumor, closest to small cell OS. The FNAC findings were confirmed on histopathology.

Pulmonary hydatidosis in a tertiary care hospital.

BACKGROUND: Hydatid disease is caused by the larval stage of Echinococcus. Liver is the most commonly involved organ followed by the lungs. Pulmonary hydatidosis can be primary or secondary. The disease may be asymptomatic for several years. Cause of concern is the fatal anaphylaxis, which may be life threatening. MATERIALS AND METHODS: The present retrospective study is over a period of ten years (2003-2012). The demographic data including the clinical features, radiological findings, other organ involvement, surgical and medical management done and histopathological findings were compiled from the records. RESULTS: During the study period a total of eight cases, five male and three female, with age ranging from eight to 43 years were diagnosed as pulmonary hydatid disease. Five patients had presented with complicated cysts. Six patients had solitary cysts involving the lung while bilateral lung involvement was seen in two cases. One patient had multiple pulmonary cysts. Three patients had associated cysts in liver and two in spleen. Surgical lobectomy was done in four cases. Histopathology showed acellular laminated ectocysts in all the cases, whereas endocyst with brood capsules was seen in five cases. CONCLUSIONS: Pulmonary hydatidosis is not uncommon. Anaphylaxis, although rarely seen, may be a disastrous event. High index of clinical suspicion and mass awareness for interruption of transmission of parasite can lead to proper treatment and possible eradication.

Evaluation of grading and hormone receptor immunostaining on fine needle aspirates in carcinoma breast.

BACKGROUND: Grading and hormone receptor determination in breast carcinoma are predictive factors for response to hormonal therapy. AIM: This study was undertaken to grade breast carcinoma and to determine estrogen receptor (ER) and progesterone receptor (PR) expression on fine-needle aspiration cytology (FNAC). Furthermore, the objective was to compare the results with histological grading and immunohistochemistry on surgical material. MATERIALS AND METHODS: Fifty cases of breast carcinoma diagnosed on FNAC were included. The cytological grading was done according to the Robinson's grading system. The corresponding histology sections were graded using the modified Bloom-Richardson system. Immunostaining for ER and PR was done on smears and tissue sections. RESULTS: On both cytological and histological evaluation, 49 cases were infiltrating ductal carcinoma and one case was colloid carcinoma. On comparing cytological and histological grading, 78% were correctly graded on cytology. The sensitivity, specificity, positive predictive value and negative predictive value for ER detection on immunocytochemistry (ICC) were 55.6%, 95%, 93.8% and 61.3%, respectively. The sensitivity, specificity, positive and negative predictive value for PR detection on ICC were 57.7%, 95.2%, 93.8% and 64.5%, respectively. The correlation for ER and PR between cytology and histology was 72.3% and 74.5%. CONCLUSION: The grading along with ER and PR immunostaining of breast carcinoma on smears is advocated because of high concordance between cytology and histology. This allows the patient to be treated with hormonal therapy on the basis of FNAC alone.

Multilocular peritoneal inclusion cyst mimicking an ovarian tumor: A case report.

Peritoneal inclusion cysts are uncommon abdominopelvic cysts seen in perimenopausal women. It is often misdiagnosed clinically as an ovarian tumor due to similar presentation and mimicking findings on radiology. We describe a perimenopausal woman presenting with pelvic mass. Her clinical finding on radiology suggested an ovarian tumor; however, biopsy revealed it as peritoneal inclusion cysts. We discuss the possible ways to avoid such mistakes.

Langerhans cell histiocytosis in children diagnosed by fine-needle aspiration.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare intricate pediatric neoplasm with varied clinical manifestations and multiple treatment modalities. AIM: To study the cytological features of LCH and the differential diagnoses on fine-needle aspiration (FNA). MATERIALS AND METHODS: FNA was performed using a 23-gauge needle fitted to a 10 mL syringe mounted on syringe holder. LCH was diagnosed on FNA smears in seven cases confined to the head and neck region, which included three cases of lymphadenopathy, three cases of scalp swelling, and one case of orbital swelling. RESULTS: The age of the patients ranged from 25 days to 11 years and male-to-female ratio was 1:1.3. Clinically, the diagnoses suggested were tuberculosis, inflammatory lesion, abscess, and malignancy. The cytologic findings included high cellularity, isolated Langerhans cells (LCs) with prominent nuclear indentation, grooves and abundant vacuolated cytoplasm, multinucleated giant cells, eosinophils, and lymphocytes. Areas of necrosis were noted in one case. Histopathology, along with positive S-100 immunohistochemistry, confirmed the diagnosis of LCH. CONCLUSIONS: LCH is a rare disease occurring predominantly in children and can be diagnosed with ease on FNA cytology by the presence of characteristic Langerhans cells. The S-100 positivity aids in suggesting a diagnosis of LCH.

Sudden cardiac death in 2 young siblings.

Hypertrophic cardiomyopathy is a disease known for exhibiting phenotypic and genetic heterogeneity. At times, sudden cardiac death may be the first and foremost manifestation of the disease. We report 2 cases of hypertrophic cardiomyopathy causing sudden death, which were diagnosed on autopsy with special emphasis on histopathological findings of this entity. The role of a pathologist cannot be undermined as the disease is a diagnostic challenge often overlooked by the neophytes in the field due to unawareness.

Direct immunofluorescence pattern and histopathological staging in alopecia areata.

AIM: The present study was designed to categorize alopecia areata (AA) into various stages based on histopathology and further study the direct immunofluorescence (DIF) pattern. MATERIALS AND METHODS: The current study is noninterventional, prospective study on 25 consecutive patients suspected of AA based on clinical assessment. Histomorphologic features and immunoreactivity for IgG, IgM, IgA, and C3, was studied on biopsy material. RESULTS: Age of the patients ranged from 6 years to 48 years with a mean age of 28.56 ± 21.8 years. Majority of patients, 9 (36%) were in the age group of 21-30 years. Of 25 patients, 13 (52%) were males and 12 (48%) were females. Male: female ratio was 1.1:1. On histopathology majority of cases were in subacute stage 9 (36%), followed by chronic 7 (28%), acute 5 (20%) and recovery stages 4 (16%). Three (12%) of 4 cases showed characteristic swarm of bees appearance. Two (8%) of the cases showed presence of giant cells. Increased numbers of catagen hair were seen in 12 (48%) cases. Of 25 cases, 9 (36%) cases showed positive DIF with granular deposits. The most common immunoreactant was IgG in 7 (28%) cases, followed by IgA in 4 (16%), C3 in 6 (24%) and IgM in 3 (12%) cases. Of 9 cases showing positive staining, 3 (12%) were in acute stage and 2 (8%) each in subacute, chronic and recovery stages. CONCLUSION: The observations further reiterate that immune mechanisms play a role in the pathogenesis of AA.

Relative value of immunohistochemistry in detection of mycobacterial antigen in suspected cases of tuberculosis in tissue sections.

BACKGROUND: The diagnosis of tuberculosis (TB) depends on identification of the infecting organism. The diagnosis presents as a challenge due to its diverse clinical presentation and low yield of acid-fast bacilli (AFB) in tissue sections. AIM: The aim of the present study is immunohistochemical localization of tubercle bacilli or their components that persist in the granulomas, but have lost the property of staining with acid-fast stain, assess the advantage of immunostaining over conventional Ziehl-Neelsen (ZN) staining and further to study the staining pattern on immunohistochemistry (IHC). MATERIALS AND METHODS: The study population comprised 100 suspected cases of TB. Tissue sections from these were subjected to hematoxylin and eosin, ZN and IHC staining using polyclonal antibody to Mycobacterium tuberculosis followed by a comparative analysis of the results. Cases of lepromatous leprosy were used as a positive control. RESULTS: Acid-fast bacilli were identified by ZN stain in 23% of cases. IHC identified 72% cases. In the present study, IHC had higher sensitivity (95.56%) and negative predictive value (96.43%), but lower specificity (35.06%) and positive predictive value (30.56%) than ZN stain which had the sensitivity, specificity, positive predictive value and negative predictive values of 30.56%, 96.43%, 95.65% and 41.56% respectively. CONCLUSION: Immunohistochemistry is a simple and sensitive technique for localization of tubercle bacilli and their components on tissue sections. It can be easily incorporated in routine histopathology laboratory and serve as an efficient diagnostic adjunct to conventional ZN staining. This will help reduce the practice of prescribing empirical antitubercular treatment based on clinical suspicion alone.

Spectrum of nonhematological pediatric tumors: A clinicopathologic study of 385 cases.

BACKGROUND: The aim of this study is to understand the epidemiology of tumors in children in our region due to a paucity of studies on the histologic review of the childhood tumors in general and benign tumors in particular. MATERIALS AND METHODS: The records of all the tumors diagnosed histopathologically in children <14 years of age during a period of 8-year (2005-2012) were reviewed. RESULTS: A total of 385 tumors were seen in the age range of 1 month-14 years with 231 (60%) in boys and 154 (40%) in girls. Highest number of cases, 224 (58.18%) were in the age group of 10-14 years. Benign tumors comprised 275 (71.43%) cases while the malignant tumors accounted for 110 (28.57%) cases. In benign tumors, vascular tumors were in majority with 68 cases, while in malignant category bone tumors were most common with 36 cases. CONCLUSIONS: Although the exact incidence rate cannot be provided by this hospital-based study, the information is useful in showing patterns of childhood tumors. We included both benign and malignant tumors, while most of the studies in the past have focused mainly on malignant tumors in children.