Langerhans cell histiocytosis of thyroid: Case report with review of literature.

Langerhans cell histiocytosis (LCH) is a rare monoclonal disease of antigen presenting cells. Involvement of thyroid gland by LCH is exceedingly rare. Herein, we present a case of LCH involving the thyroid in a 38-year-old woman. Our patient presented clinically as a case of primary thyroid neoplasm. Presence of elongated, epithelioid neoplastic cells with grooved nuclei along with presence of background eosinophils were seen on fine-needle aspiration cytology (FNAC) and histopathology. Positive staining for CD1a and S100 immunohistochemistry confirmed the diagnosis of LCH. Patient was given combination chemotherapy and has responded well to the same without any complaints for last 6 months. With this report, our goal is to expand awareness of this rare tumor in the thyroid. Consideration at the time of FNAC and its correct diagnosis on subsequent excision is imperative for patient management.

Pulmonary inflammatory myofibroblastic tumor coexisting with lymphangitis carcinomatosis: Mimicking metastatic papillary thyroid carcinoma with nodular fasciitis-like stroma.

Inflammatory myofibroblastic tumors (IMTs) are uncommon; intermediate grade soft tissue tumors occurring in young individuals with an uncertain behaviour. The incidence of pulmonary lymphangitis carcinomatosis (PLC) is around 6-8% of all pulmonary metastases. However, PLC due to papillary thyroid carcinoma (PTC) is very uncommon. We present a case of a 26-year-old male, who presented with a solitary left lung nodule on radiological scans. There was also a past history of thyroid surgery done two years back for PTC. Histology revealed a soft tissue tumor reminiscent of IMT. The periphery of the IMT nodule showed metastatic PTC in the form of extensive PLC. In view of this unusual histology, a diagnosis of PTC with nodular fasciitis-like stroma (PTC-NFS) was initially considered. However, molecular studies for anaplastic lymphoma kinase (ALK) gene rearrangement confirmed the diagnosis of IMT. This case highlights the unusual occurrence of tumor-to-tumor metastasis causing diagnostic challenges and also the importance of molecular testing.

Familial Gigantiform Cementoma with Calcium Steal Phenomenon and Social Stigma: A Case Report with Review of Literature.

Cemento-ossifying fibromas are benign fibro-osseous lesions characterized by deposition of cementum and fibrous tissue. Familial gigantiform cementoma (FGC) is an exceeding rare and distinct subtype of cemento-osseous-fibrous lesion. We hereby present a case of FGC in a young boy who was left to die due to the social stigma caused by the massive bony growth in the upper and lower jaw. The patient was somehow rescued by a non-governmental organization and underwent his surgical management at our hospital. On family screening, the mother also had similar smaller asymptomatic lesions in the jaw, but she refused further investigations and treatment. FGC is frequently associated with "calcium-steal phenomenon," which was also seen in our patient. Family screening is therefore necessary to identify asymptomatic patients in the family and follow them up with radiology and whole body dual-energy absorptiometry scans.

Eosinophilic solid cystic renal cell carcinoma: A series of 3 cases elucidating the spectrum of morphological and clinical features of an emerging new entity.

Eosinophilic solid cystic renal cell carcinoma (ESC-RCC) is a recently described entity, which demonstrates distinct clinical, pathological and molecular features. We present a series of three cases, the first to be reported from the Indian subcontinent. All three patients were over 50 years of age; and presented with a large kidney mass. One patient had a locally advanced disease while the other two presented with metastases. Microscopic examination revealed a tumor displaying solid-cystic and/or papillary areas composed of clear as well as eosinophilic cells in all three cases. On immunohistochemistry, all the three cases showed a unique CK20+/α-methyl-acyl-CoA-racemase + immunophenotype. Melan-A was focally positive in Case 2. Cytokeratin 7 was focally but strongly positive in Case 3. The two patients with metastatic disease were diagnosed on core biopsies and were advised oral tyrosine kinase inhibitor therapy. The third patient underwent upfront radical nephrectomy. Due to its peculiar morphology and immunoprofile, the diagnosis of ESC-RCC can be confidently made even on a core biopsy. Most cases reported till date had an indolent course. The metastatic presentation in two of our patients emphasizes the need to gather further evidence to ascertain the biological behavior of this emerging entity.

Gastrointestinal stromal tumor presenting with lower urinary tract symptoms - A series of five cases with unusual clinical presentation.

Spindle cell tumors of the prostate are very uncommon and the majority involve the prostate secondarily from adjacent organs. Gastrointestinal stromal tumors (GISTs) are specific C-kit (CD 117) expressing mesenchymal tumors occurring in the gastrointestinal tract, commonly in the stomach and intestine; however, it is seldom seen involving the prostate. Although primary prostatic GISTs have been described, majority of them are secondary involvement from rectal GIST. The patient usually presents with urinary tract symptoms or prostate enlargement simulating a prostatic neoplasm. GIST as a differential diagnosis for prostatic mass is never thought of. We present a series of five cases of GIST arising from/involving the prostate mimicking a primary prostatic malignancy and the challenges associated with them for diagnosis and treatment.

Overexpression and purification of folded domain of prostate cancer related proteins MSMB and PSA.

Overexpression of domains of a human protein using recombinant DNA technology has been challenging because individual domains intend to accumulate as non-soluble aggregate when expressed separately. Studies on identifying right sequences for a domain to be able to fold independently may help understand the folding pattern and underlying protein-engineering events to isolate the functional domains of a protein. In this report, individual domains of prostate cancer related biomarkers; MSMB and PSA were overexpressed in bacterial system and purified in their folded forms using affinity chromatography. The western blotting experiment using domain specific antibodies further confirmed these proteins. The designed nucleotide sequences domains were truncated using fold index software and folding were predicted by phyre2 and I-TASSER software. Other parameters were optimized for their overexpression and purification using Co-NTA affinity chromatography. Purified domains of each protein showed secondary structures such as α + ß type for PSA, α/ß and ß type for the each domains of PSA and MSMB respectively. This is the first report on producing PSA and MSMB individual domains in functional folded forms. This study may help produce the folded domain of many such proteins to be used for better diagnostic purpose.

Natural antioxidant biomolecules promises future nanomedicine based therapy for cataract.

Cataract is an eye disease of major human concern and its prevention is important to control the global incidences of blindness. The emergence of cataract in the eye lens by strong UV radiation and growing pollution could be effectively reduced by natural antioxidant biomolecules such as flavonoids, phenolic acids, carotenoids and vitamins. This goal can be achieved either by direct external use of antioxidant biomolecules in the form of topical application as an eye drops, food supplements or through nanobiotechnology based formulation without any side effects. In this manuscript, we have discussed the mechanisms of cataract formation and the preventive role of different classes of natural antioxidant biomolecules. Further, role of nanobiotechnology to enhance therapeutic potential of these natural antioxidant molecules by enhancing solubility, stability, bioavailability and sustained release has been briefly discussed.

A novel serine protease cryptolepain from Cryptolepis buchanani: purification and biochemical characterization.

A novel protease is purified to homogeneity from the latex of a medicinally important plant Cryptolepis buchanani of family Apocynaceae (formerly Asclepiadaceae). The enzyme named cryptolepain has a molecular mass of 50.5 kDa. The isoelectric point and extinction coefficient (epsilon280nm1%) are 6.0 and 26.4, respectively. Cryptolepain contains 15 tryptophans, 41 tyrosines, and eight cysteine residues forming four disulfide bridges. The detectable carbohydrate moiety in the enzyme was found to be 6-7%. Cryptolepain hydrolyzes denatured natural substrates like casein, azocasein, and azoalbumin with high specific activity. The protease is exclusively inhibited by serine protease inhibitors phenylmethansulfonyl fluoride and diisopropyl fluorophosphate. Hydrolysis of azoalbumin by the cryptolepain is optimal in the pH range of 8-10 and temperatures of 65-75 degrees C. The enzyme shows high stability against pH (2.5-11.5), temperature (up to 80 degrees C), and chemical denaturants. The Km value of the enzyme was found to be 10 microM with azocasein as the substrate. The N-terminal sequence of cryptolepain is unique and shows only little homology to other known serine proteases, which makes this enzyme an ideal candidate for our ongoing biochemical and structure-function investigations of proteases. Easy availability of the latex and simple purification procedures make the enzyme a good system for exploring the biophysical chemistry of serine proteases as well as applications in the food industry.

Highly stable glycosylated serine protease from the medicinal plant Euphorbia milii.

A serine protease, named as "Milin" was purified to homogeneity from the latex of Euphorbia milii, a medicinal plant of Euphorbiaceae family. The molecular mass (SDS-PAGE), optimum pH and temperature of the enzyme were 51kDa, pH 8.0 and 60 degrees C, respectively. Milin retains full proteolytic activity over a wide range of pH (5.5-12) and temperature (up to 65 degrees C) with casein and azoalbumin as substrates. The activity of milin is inhibited by serine proteases inhibitors like PMSF, APMSF and DFP, but not by any other protease inhibitors such as E-64 and PCMB. Like the other serine proteases from the genus Euphorbia, the activity of milin was not inhibited by the proteinaceous inhibitor soyabean trypsin inhibitor (SBTI) even at very high concentrations that is naturally present in plants. The specific extinction coefficient (epsilon(280 nm)(1%)), molar extinction coefficient (a(m)) and isoelectric point of the enzyme were found to be 29, 152,500 M(-1) cm(-1) and pH 7.2, respectively. The enzyme is a glycoprotein with detectable carbohydrate moiety (7-8%) in its constitution, which is essential for the activity. The numbers of tryptophan, tyrosine and cysteine residues in the sequence of milin were estimated chemically and are 23, 14 and 14, respectively. Of the 14-cysteine residues, 12 constituted 6-disulfide linkages while two are free cysteines. The N-terminal sequence (first 12 amino acid residues) was determined and does not match with any sequence of known plant serine proteases. Perturbation studies by temperature, pH and chaotropes of the enzyme also reveal its high stability as seen by CD, fluorescence and proteolytic activity. Thus, this serine protease may have potential applications in food industry.