Pitfalls in Cytological Diagnosis of Extra Adrenal Paraganglioma and Pheochromocytoma: Experience From a Tertiary Care Center.

BACKGROUND: Pheochromocytoma and extra-adrenal paragangliomas increasingly coming into light nowadays because of improved imaging techniques and biochemical investigations. There is sparse literature available regarding cytological findings of adrenal and extra-adrenal paragangliomas. MATERIAL AND METHODS: We studied 16 cytological specimens retrospectively over a period of 3 years, where subsequent histological diagnosis of phaeochromocytoma or paraganglioma was available. RESULTS: A total of 16 cytology specimens were studied. Nine patients had adrenal SOLs and seven patients had extra-adrenal lesions. Age range was 12 to 60 years Majority of the cytology smears were cellular (87.5%). The smears were composed of small clusters as well as dispersed plasmacytoid cells with eccentric nuclei containing salt and pepper chromatin and moderate to abundant granular cytoplasm. Large cellular clusters mimicking the Zellballen pattern was present in one case. Anisonucleosis was mild to moderate, except in three cases where marked anisonucleosis posed diagnostic challenges. The background was hemorrhagic in all cases, however, two cases in addition had necroinflammatory background. All cases lacked mitotic activity and cytoplasm was delicate with indistinct cell borders. Bare oval nuclei were a frequent finding. Nuclear grooves or cytoplasmic vacuoles were absent. In 12 out of 16 cases, the initial cytological diagnosis correlated with final histological diagnosis, with an overall diagnostic accuracy of 75%. Four misdiagnosed cases had some atypical cytological features like marked anisonucleosis, necroinflammatory background, and presence of prominent nucleoli. CONCLUSION: Here we have highlighted some of the distinguishing cytological features that can help in cytological diagnosis of paragangliomas. Hemorrhagic background with plasmacytoid morphology, granular cytoplasm, naked nuclei, and absence of mitosis are useful clues.

Clinicopathological study of adrenal pheochromocytoma and extra-adrenal paragangliomas with reference to GAPP and PASS scoring systems.

BACKGROUND: The presence of distant metastasis is known to drastically reduce survival of adrenal pheochromocytoma (PH) and extra-adrenal paraganglioma (PGL). Therefore, predicting malignant potential has an immense impact on prognosis. Pheochtomocytoma of adrenal gland scaled score (PASS) and the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score are two histological algorithms used to predict metastatic potential, but neither has been regarded as 'gold-standard'. Both these scoring systems are yet to be validated. Here, we tried to validate the association of GAPP/PASS scores with disease outcome and strength of association between individual GAPP/PASS parameters with prognosis. MATERIALS AND METHODS: This was a prospective study comprising 22 pheochromocytomas and eight paragangliomas. GAPP score was calculated in paraganglioma cases, and both GAPP/PASS scores were calculated for pheochromocytomas. Disease outcome was then tallied with risk stratification of the GAPP/PASS scoring system. Succinate dehydrogenase B (SDHB) immunohistochemistry was done in 15 cases to see its impact on prognosis. RESULTS: The common PASS parameters associated with malignancy were 'high cellularity', 'tumor cell spindling' and 'extension into adipose tissue'. PASS score showed high sensitivity and negative predictive value but low specificity and positive predictive value. Similarly, GAPP score also showed high sensitivity and negative predictive value but low specificity and positive predictive value. CONCLUSION: In our study, GAPP/PASS scores successfully segregated tumor with low malignant potential from tumor with higher risk of metastasis, although specificity of GAPP was more than PASS. We also found that addition of objective parameters like SDHB immunohistochemistry may further increase the specificity of the existing scoring system.

Efficacy and safety of an early response-based tapering regimen of tocilizumab in children with systemic juvenile idiopathic arthritis.

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is a distinct disease subset, with a poorer prognosis compared with other JIA subsets. Tocilizumab has an important role in the management of sJIA refractory to standard initial therapy. However, no specific guidelines exist for the tapering of tocilizumab therapy in sJIA, which could have implications on the overall cost and side effects of treatment. METHODS: This was an observational study which included 21 children with refractory sJIA, who were initially put on injection tocilizumab every 2 weekly, with subsequent dosing tapered to 4 weekly and 6 weekly intervals based on JIA ACR 70 responses at 12 and 24 weeks, respectively. The primary outcome at week 36 included JIA ACR 30, 50, 70, and 90 response rates with other efficacy and safety measures as secondary outcomes. RESULTS: At 36 weeks, JIA ACR 30, 50, 70, and 90 responses were observed in 90.5%, 90.5%, 71.4%, and 52.4% patients respectively along with significant improvement in hematological and inflammatory parameters. The mean prednisolone dose could be reduced from 0.54 to 0.13 mg/kg/day and around 29% patients were able to discontinue steroids altogether. No serious adverse events were recorded. With drug tapering, we could curtail on 26% of the total tocilizumab dose that would have been otherwise required on the continuous 2 weekly protocol. CONCLUSIONS: Tocilizumab, used in an early response-based tapering regimen, was both safe and efficacious in children with sJIA refractory to standard therapy. Larger and longer duration studies are required to further validate our observations.

Uncovering tetrazoles as building blocks for constructing discrete and polymeric assemblies.

Metal-organic self-assembly with flexible moieties is a budding field of research due to the possibility of the formation of unique architectures. Tetrazole, characterised by four nitrogen atoms in a five-member ring, exhibits immense potential as a component. Tetrazole offers four coordination sites for binding to the metal centre with nine distinct binding modes, leading to various assemblies. This review highlights different polymeric and discrete tetrazole-based assemblies and their functions. The meticulous manipulation of stoichiometry, ligands, and metal ions required for constructing discrete assemblies has also been discussed. The different applications of these architectures in separation, catalysis and detection have also been accentuated. The latter section of the review consolidates tetrazole-based cage composites, highlighting their applications in cell imaging and photocatalytic applications.

A case of superficial CD34 positive fibroblastic tumor: Diagnostic challenges and pitfalls.

ABSTRACT: Superficial CD34 positive fibroblastic tumor (SCPFT) is a recently described soft tissue tumor of intermediate grade with predilection for subcutaneous and superficial fascial planes. Morphological diagnosis of these tumors can be challenging because of overlapping features with other benign and malignant soft tissue tumors of fibroblastic and myofibroblastic origin. A middle-aged man came with a subcutaneous mass in the left thigh. Microscopic examination showed features of an SCPFT comprised of a circumscribed spindle cell tumor with focal striking pleomorphism and bizarre hyperchromatic nuclei. Immunohistochemically (IHC), the tumor cells showed diffuse positivity for CD34 and focally for cytokeratin. Diagnosis of SCPFT on the basis of morphology alone can be challenging. A constellation of clinicoradiological profiles, IHC features, and sometimes molecular studies clinch the definitive diagnosis which can be helpful in avoiding overtreatment and chemotherapy. Here we highlight the diagnostic challenges and pitfalls in a case of SCPFT.

Cytological findings of phosphaturic mesenchymal tumor: Report of a case with summary of prior published cases.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing tumor-induced osteomalacia (TIO) and is characterized by secretion of FGF23, renal phosphate wasting and hypophosphataemia. It can be completely cured by resection and therefore its diagnosis is of utmost importance. Although the histology is well described, there is sparse literature on cytology of PMT and only three cases have been described so far. A 45-year-old lady presented with a non-tender mass in hard palate for 2 years from which fine-needle aspiration was done. The smears were paucicellular and showed bland spindle cells embedded in osteoid-like stromal matrix in a hemorrhagic background. Here we take the opportunity to describe the cytological findings of PMT along with its cytological differentials and a summary of prior published cases.

Testicular Mixed Teratoma and Yolk Sac Tumor, Prepubertal Type: A Case Report with Summary of Prior Published Cases.

BACKGROUND: Testicular mixed germ cell tumor is common in the post-pubertal age, less so in prepuberty. There are only 3 reports of prepubertal mixed teratoma and yolk sac tumor. Two of these cases had immature teratoma component and were in the neonatal age group. The third case in a toddler had a mature teratoma component. CASE REPORT: An 18-month-old boy presented with a testicular mass. Serum AFP was elevated (2200 ng/ml). The orchidectomy specimen contained a yolk-sac tumor and a small epidermoid cyst, indicating a mature teratomatous component. CONCLUSION: We report a testicular mixed teratoma and yolk sac tumor, prepubertal type along with summary of prior published cases. There is only one report describing this combination of mature teratoma with yolk sac tumor in the prepubertal testis.

Refractory Takayasu arteritis with recurrent pyoderma gangrenosum: a therapeutic challenge with case-based review.

Takayasu arteritis (TA) is an uncommon chronic granulomatous large-vessel vasculitis affecting the aorta and its branches. Pyoderma gangrenosum (PG) is a chronic neutrophilic dermatosis characterized by rapidly developing painful ulcers. The association of PG with TA is relatively uncommon. We report a case of a 22-year-old lady with a history of recurrent pyoderma lesions for 4 months following which she developed right upper limb claudication. She underwent contrast-enhanced magnetic resonance angiography of the aorta and its branches and was initially diagnosed with type IIb TA. She was put on prednisolone and methotrexate but had a major relapse with new-onset lower limb claudication despite an appropriate course of immunosuppression. She was planned for tocilizumab infusion 8 mg/kg intravenous every 4 weeks. Following the first dose of tocilizumab, her vascular symptoms improved but she had a flare of PG. This was followed by another flare after the second dose. She was switched to tofacitinib which led to sustained remission of her TA activity and healing of her skin lesions, and the prednisolone dose could be reduced to 5 mg daily over the next 1 year. Various immunosuppressives were used to date for treating PG in TA. However, tofacitinib is being reported for the first time in literature for treating PG and controlling TA activity. The paradoxical flare of PG with tocilizumab is quite uncommon and is also reported in our case with literature review.

Adrenal and Mesenteric Teratomas in Infants: Common Tumors in Uncommon Sites.

Teratomas are common tumors in children. The most common sites are gonads, however, several extragonadal sites are well known such as sacrococcygeal region, mediastinum, head and neck, stomach, and vagina. Occasionally, teratomas occur in unusual sites which pose diagnostic difficulties. Here, we describe two cases of infantile teratomas with unusual presentation. The first case was a 6-month-old girl who presented with a mass in the right side of the abdomen. Computed tomography (CT) scan showed a solid-cystic mass in the right suprarenal region. The second was a 4-month-old boy who came with a huge abdominal mass. Contrast-enhanced CT showed a tumor arising from the jejunal mesentery. On microscopic examination, they were diagnosed as mature and immature teratoma, respectively. Although neuroblastoma is the most common infantile adrenal neoplasm, the possibility of teratoma should be considered for cystic adrenal lesions. Mesenteric teratoma can be difficult to distinguish radiologically from the more common lymphangioma; however, accurate diagnosis is important in view of long-term follow-up for teratomas because of the possibility of malignant transformation.

Intramyofiber skeletal muscle invasion: An unusual pattern of muscle infiltration in breast cancer.

Skeletal muscle infiltration in carcinoma is a rare entity. Intramyofiber skeletal muscle invasion is the rarest type of muscle infiltration. Here we present one such case of intramyofiber skeletal muscle invasion in a case of breast carcinoma.

Congenital Sacrococcygeal Neuroblastoma: A Report of Two Cases with Summary of Prior Published Cases.

BackgroundNeuroblastoma can arise from extra-adrenal sites in the paraspinal sympathetic chain, including the presacral region, where they must be differentiated from an immature or malignant neural lesion arising from a teratoma.Case ReportWe describe two congenital presacral neuroblastomas. The main clinical differential diagnoses were sacrococcygeal teratoma and meningomyelocele. Pathologically, they lacked teratomatous tissues, lacked germ cell serum markers, were localized without metastases, and were MYCN non-amplified. Both patients have done well without chemotherapy at 18 and 15 months of follow-up.ConclusionCongenital presacral neuroblastoma should be differentiated from teratomatous lesions, and in general have a good prognosis.

Infantile Myofibroma: A Report of Two Cases with Differential Diagnoses.

Infantile myofibromas (IMs) are benign soft-tissue tumors of children. They are of fibroblastic-myofibroblastic origin and show considerable morphological overlap with other spindle cell neoplasms. Here, we present two cases of solitary myofibromas, one in a neonate and one in a 2-year-old girl. A 2-day-old girl presented with severe respiratory distress and died during intubation. At autopsy, a myofibroma involving the oropharynx with extension up to the larynx was noted. Second case was a 2-year-girl with a myofibroma in the hard palate. IM must be differentiated from other benign and malignant spindle cell tumors of infancy and childhood. Oropharyngeal myofibroma should be considered in the differentials of neonatal respiratory distress.

Infantile Myofibroma: A Series of 2 Cases with Special Reference to Cytological Features.

BackgroundInfantile myofibromas (IM) are benign soft tissue lesions of childhood and represent a significant portion of the benign spectrum of fibroblastic-myofibroblastic tumors. Cytological diagnosis of these tumors can be challenging because of overlapping morphology and limited case report descriptions. We describe the cytological features and the cytological differential diagnoses.Case reportWe describe cytological features of two IMs. The main features were the presence of loose clusters and dispersed bland myofibroblasts in varying stages of maturation with traversing blood vessels and myxoid stroma. The cells typically lacked features of atypia, mitoses and significant pleomorphism.ConclusionDiagnosis of IM on the basis of cytology alone can be tricky and definitive diagnosis should be made only after correlating the cytological features with histology. However, bland morphology of differentiating myofibroblasts can aid in cytological diagnosis and help to exclude other malignant spindle cells neoplasms needing preoperative chemotherapy.

Double parasite in appendicectomy specimen: Causal factor or incidental finding?

Appendicitis is the most common cause of acute abdomen leading to invasive surgery. While the mainstay treatment of appendicitis is appendicectomy, there are a few conditions where conservative medical treatment cures the patient. One such condition is intestinal parasitosis, where only pharmacotherapy causes remission. Although Enterobius vermicularis is the commonest parasite in this regard, others such as Schistosoma, Taenia, Ascaris and Trichuris can also be found. Coexistence of two parasites in appendicectomy specimen is distinctly rare. We present one such case here of double infestation with Enterobius and Trichuris in the appendix.

Measurement of bone mineral density by dual energy X-ray absorptiometry in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate bone mineral density using dual X-ray absorptiometry in Juvenile Idiopathic Arthritis (JIA) patients and factors affecting it, if any. METHODS: A cross sectional study was conducted by enrolling thirty five patients of JIA and age and sex matched controls. Bone Mineral Density (BMD) and Z score of whole body, total body less head, lumbar spine and distal radius were obtained and adjusted for age, sex, weight and BMI in both cases and controls. Dietary intake of calcium, vitamin D intake, sunlight exposure, weight bearing physical activity, age of onset, duration of disease, disease activity score and treatment received (prednisolone and methotrexate) were recorded. RESULTS: BMD was significantly lower among patients as compared to controls. Decreased dietary intake of vitamin D and calcium, decreased weight bearing physical activity and sunlight exposure were the major factors for low BMD. Use of steroid also decreased BMD to some extent, whereas use of methotrexate, disease duration and severity did not have a significant correlation with BMD. CONCLUSIONS: Apart from disease control, it is important to improve the dietary intake of calcium, vitamin D and encourage more physical activities and exposure to sunlight in JIA patients.

Plasmodium vivax presenting as acute glomerulonephritis in a 3-year-old child.

Although acute glomerulonephritis is a rare complication of Plasmodium falciparum malaria, it has not been reported in connection with Plasmodium vivax. We report a case of complicated P. vivax malaria presenting as acute glomerulonephritis. A three-year-old boy presented with high grade fever, a seven-day history of the progressive swelling of his body and a one-day history of vomiting. An examination revealed hypertension (>95th percentile), pallor and hepatosplenomegaly. Investigations showed a platelet count 80,000/mm(3) with haematuria [20-30 red blood cells/high power field with more than 80% dysmorphic red blood cells]. A peripheral smear showed the presence of trophozoites of P. vivax. The patient was diagnosed as having P. vivax causing acute glomerulonephritis and was treated successfully with antimalarials and enalapril. With the changing epidemiological pattern of malaria, especially in endemic areas, unusual complications such as acute glomerulonephritis may sometimes present in cases of P. vivax malaria.