Sensory ataxic polyneuropathy unmasking late-onset urea cycle defect.

A 63-year-old man with type 2 diabetes mellitus, alcohol consumption in moderation, and three episodes of hepatic encephalopathy presented with symmetrical lower limb distal weakness, sensory ataxia, thickened palpable nerves, mood disturbances for seven years, and a family history of schizophreniform disorders. Nerve conduction studies showed demyelinating sensorimotor polyradiculoneuropathy. CSF analysis showed mild albumino-cytological dissociation. MRI brain and lumbosacral plexus showed thickened fifth cranial nerves and lumbosacral roots. He was treated with steroids for a provisional diagnosis of chronic inflammatory polyneuropathy and became encephalopathic. EEG showed triphasic waves. Serum ammonia was 201 micrograms/dL. Further evaluation suggested ornithine transcarbamylase (OTC) deficiency. The patient underwent hemodialysis with a low protein diet, rifaximin, and sodium benzoate, with subsequent recovery.

Primary Diffuse Leptomeningeal Melanomatosis in an Indian Child With Review of Literature.

BACKGROUND: Primary diffuse leptomeningeal melanomatosis (PDLM) is an extremely rare, aggressive malignant neoplasia of the central nervous system. We report the first case of pediatric PDLM from India. METHODS: A review of literature was done to describe the 15 pediatric cases reported so far. RESULTS: A 12-year-old male child presented with fever, vomiting, and headache for 2 months. Cerebrospinal fluid examination was normal. An MRI of the brain revealed hydrocephalus, for which antitubercular therapy was started and external ventricular drainage followed by ventriculoperitoneal shunt was done. Repeat MRI revealed a suprasellar lesion, nodular enhancement of cranial nerves along with dural enhancement of spinal cord with arachnoiditis, and long-segment myelomalacia. Repeat cerebrospinal fluid examination was negative for malignant cells. During biopsy, blackish dura with diffuse blackish deposits in ventricle were noted. Histopathological examination revealed tumor cells with intracytoplasmic coarse brown pigment melanoma, frequent mitotic figures, and immunohistochemistry testing was positive for human melanoma black-45 and MelanA, suggestive of PDLM. He expired 4 months after the diagnosis. CONCLUSION: Diagnosing PDLM can be daunting in light of its slow but malignant progression mimicking TBM leading to improper management. However, the absence of any supportive microbiological evidence and failure to respond to the standard antitubercular therapy with subsequent progression of the symptoms should prompt the need for finding an alternative diagnosis. A targeted molecular diagnosis and precision medicine may provide a favorable outcome in children with PDLM.

Epithelial myoepithelial carcinoma of the parotid gland with high-grade transformation.

A woman presented with a painless swelling in front of her right auricle, which, on examination, seemed to be a hard, immobile mass arising from the right parotid gland. CT scan showed a heterogeneously enhancing mass lesion in the superficial lobe of the parotid gland with partial extension into the deep lobe. Fine needle aspiration cytology suggested a high-grade transformation (HGT) with the presence of bizarre tumour cells. She underwent a right-sided total parotidectomy with transient facial neuropraxia in the postoperative period. The final pathological diagnosis of the specimen came out to be epithelial myoepithelial carcinoma with HGT, which is a relatively rare entity, with no defined guidelines for management. Our patient was managed by surgical resection alone without any postoperative radiation therapy, and short-term follow-up results seem to suggest no recurrence.

A thylakoid biogenesis BtpA protein is required for the initial step of tetrapyrrole biosynthesis in cyanobacteria.

Biogenesis of the photosynthetic apparatus requires complicated molecular machinery, individual components of which are either poorly characterized or unknown. The BtpA protein has been described as a factor required for the stability of photosystem I (PSI) in cyanobacteria; however, how the BtpA stabilized PSI remains unexplained. To clarify the role of BtpA, we constructed and characterized the btpA-null mutant (ΔbtpA) in the cyanobacterium Synechocystis sp. PCC 6803. The mutant contained only c. 1% of chlorophyll and nearly no thylakoid membranes. However, this strain, growing only in the presence of glucose, was genetically unstable and readily generated suppressor mutations that restore the photoautotrophy. Two suppressor mutations were mapped into the hemA gene encoding glutamyl-tRNA reductase (GluTR) - the first enzyme of tetrapyrrole biosynthesis. Indeed, the GluTR was not detectable in the ΔbtpA mutant and the suppressor mutations restored biosynthesis of tetrapyrroles and photoautotrophy by increased GluTR expression or by improved GluTR stability/processivity. We further demonstrated that GluTR associates with a large BtpA oligomer and that BtpA is required for the stability of GluTR. Our results show that the BtpA protein is involved in the biogenesis of photosystems at the level of regulation of tetrapyrrole biosynthesis.

Lymph node involvement in an ovarian borderline serous tumor: a rare clinicopathologic presentation with management dilemma.

Borderline serous tumor (BST), earlier known as atypical proliferative serous tumor, is an ovarian neoplasm of low malignant potential. Extraovarian spread in the form of peritoneal implants is common in these tumors; however, lymph node (LN) involvement is infrequent. The prognostic implication of LN involvement in BST is controversial. We present a case of a 25-year-old female presenting with dull-aching abdominal pain in the left iliac fossa for the past 3 years, which was associated with constipation and abdominal bloating. Her serum Cancer antigen 125 (CA125) level was 841.3 units/ml. Pelvic ultrasonography and magnetic resonance imaging showed a large well-defined, solid-cystic, abdominopelvic mass arising from the right ovary, measuring 21×18×10 cm. The left ovary was also solid-cystic and measured 7×4×3 cm. A provisional clinico-radiologic diagnosis of ovarian malignancy was rendered. The patient underwent bilateral salpingo-oophorectomy with omentectomy and right-sided pelvic and para-aortic lymph node dissection. Histopathology revealed bilateral ovarian BST with involvement of pelvic and para-aortic lymph nodes. This was followed by adjuvant chemotherapy (in view of stage IIIA). She is disease-free at 3 years of regular follow-up. The prognosis and management of BST with LN is not yet fully elucidated. Nevertheless, the finding of such an involvement mandates thorough sampling of the primary ovarian tumor to exclude a possibility of low-grade serous carcinoma with LN metastasis.

Cytohistological and Immunohistochemical Correlation of Cutaneous Mixed Tumors: A Series of Four Cases and Review of Recent Molecular Updates.

Fine needle aspiration cytology (FNAC) is an established diagnostic modality today, but its utilization in skin tumors is limited by the fact that most of these lesions are small and easily accessible for clinicians to perform an excision biopsy. As a result, our knowledge of the cytological features of some of the uncommonly encountered skin tumors is still lacking. The aim of this study was to correlate the cytological features of cutaneous mixed tumors (CMTs) with histological and immunohistochemical findings in four cases of CMT in commonly and uncommonly encountered locations. We also review the recent updates highlighting the various genetic rearrangements and newer more specific immunohistochemical markers described so far. This was a retrospective study, and all the slides were taken from our departmental archives. Case 1 was a 25-year-old male who presented with a gradually increasing painless swelling over the right angle of the mouth of 1.5 years duration. Case 2 was a 45-year-old male with swelling on the right forearm for the last three years. Case 3 was a 35-year-old female with a forehead swelling of one year duration. Case 4 was a 55-year-old female with left cheek swelling for two years. On clinical examination, all four nodular swellings were predominantly in the skin/subcutaneous tissue. On cytology, all cases showed abundant chondromyxoid material with clusters of benign epithelial cells and a fair number of predominantly singly scattered myoepithelial cells. The diagnosis of all four cases was further confirmed on histopathology and immunohistochemistry, and the findings correlated well with cytology. The cytological features of CMT closely correlate with their histopathological and immunohistochemical features. Newer immunohistochemistry (IHC) marker pleomorphic adenoma gene 1 (PLAG1) may be helpful in making a definitive diagnosis of CMT on cytology and cell block preparation along with a good clinical correlation. Complete surgical excision is the treatment of choice, and recurrence is rare.

Carcinosarcoma of the Esophagus-A Diagnostic Challenge.

Background: Esophageal carcinosarcoma is an uncommon histologic variant of esophageal malignancy, occurring in approximately 0.5% to 2.8% of patients. Esophageal carcinosarcoma usually involves the middle and lower esophagus and consists of both epithelial and mesenchymal components. Case Report: A 54-year-old male presented with painless progressive dysphagia associated with loss of weight for 2 months. Esophagogastroduodenoscopy suggested an ulceroproliferative polypoidal growth in the lower thoracic esophagus. Biopsies from the growth showed leiomyosarcoma with tumor cells immunopositive for vimentin, h-Caldesmon, and smooth muscle actin and negative for pan-cytokeratin. Imaging suggested a heterogeneously enhancing polypoidal growth arising in the lower third of the esophagus. Thoracoscopic-assisted McKeown esophagectomy with gastric pull-up and standard 2-field lymphadenectomy was performed. A minor epithelial component was identified on final pathologic examination in addition to the leiomyosarcoma found on the preoperative biopsy. This epithelial component was invasive squamous cell carcinoma and was positive for pan-cytokeratin and p40, both of which were negative in the sarcomatous component. The patient received 4 cycles of adjuvant chemotherapy (carboplatin and paclitaxel). However, he developed a recurrence in the left cervical lymph node 4 months after adjuvant treatment and died 2 months after the diagnosis of recurrence. Conclusion: Carcinosarcoma can be easily missed in the presence of predominantly sarcomatous components even on immunohistochemical analysis. These tumors may be associated with poor prognosis and may have early recurrence despite surgery and adjuvant treatment.

Is Hypoglycemia Secondary to Metastatic Retroperitoneal Sarcoma - A Therapeutic Challenge? Case Report and Review of Literature.

Most soft tissue sarcomas afflict the extremities; however, the retro peritoneum can also be affected rarely. Retroperitoneal sarcomas are relatively asymptomatic. Although tumor-induced hypoglycemia is rare in tumors other than insulinomas, extrapancreatic tumors are a subset that displays this phenomenon. The occurrence of hypo-insulinemic hypoglycemia with low GH and IGF-1 should prompt consideration of the secretion of a hypoglycemic substance impeding the secretion of insulin and GH, such as IGF-2 or one of its related substances. The present case report is of a 38-year-old male with retroperitoneal round cell sarcoma with liver metastasis with severe symptomatic hypoglycemia who was managed with multipronged symptomatic therapy and oncological management after which he had shown significant improvement in hypoglycemic episodes and symptom profile. A literature review revealed our case report to be the first reported case of a young male (preponderance in the older population) with hypoglycemia associated with retroperitoneal sarcoma which presented with liver metastasis and the only one treated with Gemcitabine /Docetaxel. The presence of these features might point toward a poorer prognosis in a disease with an already dismal course. All these points towards the need for further research regarding intensified oncological treatment after evidence-based prognostication of high-risk groups and modalities for the management of symptomatic hypoglycemia such as Somatostatin analogs and glucagon which aid in symptom control.

Primary retroperitoneal fibrosis presenting as a renal mass.

A 67-year-old male was incidentally found to have a large left perinephric mass with a poorly functioning left kidney. A differential diagnosis of renal cell carcinoma, lymphoma, retroperitoneal fibrosis (RPF), and IgG4 renal disease was suggested on imaging studies and biopsy of the mass. A left radical nephrectomy was performed as malignancy could not be ruled out. The final diagnosis was RPF without periaortitis and the patient is doing well at 9 months of follow-up. RPF, although characterized as a manifestation of periaortitis and large vessel vasculitis, might also present as an isolated perinephric mass without aortic involvement. Surgical management is an alternative, especially when malignancy is suspected.

Mucormycosis: An Epidemic Complicating the COVID-19 Pandemic.

COVID-19 is a relatively new disease whose complete pathogenesis and complications have not been elucidated. Apart from the morbidity and mortality caused by the virus itself, it is noted that patients affected with this virus have a higher susceptibility to bacterial and fungal co-infections. Mucormycosis is a rare and life-threatening fungal infection generally associated with uncontrolled diabetes mellitus and immunosuppression. It tends to rapid disease progression and poor prognosis if not diagnosed and managed promptly. There has been a sudden increase in the number of mucormycosis cases in patients with moderate to severe COVID-19 infection in the past few months. Herein, we present a series of 10 mucormycosis cases diagnosed over one week.

Late Onset Pompe's Disease: Clinical, Pathological & Molecular Analysis of Two Adolescent Patients.

INTRODUCTION: The estimated global prevalence of late onset Pompe's disease is 1/57000 live birth(1). We present the case of two patients diagnosed to have Pompe's disease with a rare association of cardiomyopathy. MATERIALS: Two siblings born out of non consanguineous marriage presented with proximal myopathy of 5 years duration. Patient 1 - 19 year female, there was atrophy and weakness of face, neck, girdle and limbs. Her Echocardiogram showed LV dilation with low ejection fraction, ECG showed LV hypertrophy with incomplete LBBB. Her CK-NAC values came to be 918 U/L. Patient 2 - 16 year male; progression, distribution and severity slightly different to his sister but had exertional dyspnea since last one year. His echocardiogram showed LV diastolic dysfunction, ECG showed short PR interval partial LBBB and his CK-NAC came to be 2347 U/L. His skeletal muscle biopsy showed deposition of glycogen. Genetic analysis revealed pathogenic mutation in GAA gene (c.2040G>A) in both patients. RESULT: Late onset Pompe disease is of less severity but progressive. The involvement of heart is less likely compared to infantile onset(2). It is also interesting that the same variant presents differently in both patients. CONCLUSION: Genetic diseases manifest as rare phenotype which in itself is a clinical puzzle. When rare disease present with a rare manifestation of itself, this pose a great diagnostic challenge. Pompe's disease is one of the very few inherited disorder which has definitive treatment- enzyme replacement therapy. Molecular characterization of the variant is absolutely necessary before initiating therapy. References Ausems MG, Verbiest J, Hermans MM, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet 1999;7(6):713-716. Van der Beek NA, Soliman OI, Van Capelle CI, et al. Cardiac evaluation in children and adults with Pompe disease sharing the common c.-32-13T>G genotype rarely reveals abnormalities. J Neurol Sci 2008;275(1-2):46-50.

Synchronous multicentric giant cell tumour of immature skeleton with epiphysiometaphyseal origin.

Giant cell tumour of bone accounts for 5% of all primary bone tumours. Multicentric giant cell tumour is an infrequent variety be it either synchronous or metachronous accounting for less than 1% of all giant cell tumours. Synchronous multicentric giant cell tumour of foot and ankle with epiphysiometaphyseal origin is unheard of. We delineate a case of soap-bubble appearance lytic lesions at left distal tibia and talus in an early adolescent woman with biopsy proven giant cell tumour for its rarity and its successful management by extended curettage and allogenic impaction bone grafting.

Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases.

BACKGROUND: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. AIMS: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. MATERIALS AND METHODS: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. RESULTS: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. LIMITATIONS: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. CONCLUSION: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

Metastasis from Cervical Cancer Presenting as a Pancreatic Head Mass - an Unexpected Diagnosis!

Cervical cancer is the most common malignancy in Indian women. After primary treatment, distant recurrence is rare and occurs at liver, lung or bone. Distant metastases to other abdominal sites are very rare. We present a case of pancreatic metastasis from cervical cancer, which has not been reported in literature. A 53-year-old woman presented with 3-month history of dull upper abdominal pain with anorexia and weight loss. Past medical history revealed a stage 3c squamous cell carcinoma (SCC) cervix treated by chemo-radiotherapy 2 years back. Contrast CT abdomen showed a pancreatic head mass encasing portal vein. CA-19.9 was 30.8 U/ml. 18-Fluorodeoxyglucose(FDG) PET/CT whole body scan showed avid pancreatic head mass and right lung nodule with no uptake in utero-cervix, adnexae or pelvic nodes. Endoscopic ultrasound-guided needle aspiration from the mass showed metastatic SCC, confirming pancreatic metastasis from SCC cervix with no active disease at the cervix. Being aware of recurrence at such atypical locations during post-treatment follow-up, helps in accurate diagnosis and appropriate treatment.

Marked Facial Weakness, Ptosis, and Hanging Jaw: A Case with RYR1 -Related Congenital Centronuclear Myopathy.

Congenital myopathies are an expanding spectrum of neuromuscular disorders with early infantile or childhood onset hypotonia and slowly or nonprogressive skeletal muscle weakness. RYR1 -related myopathies are the most common and frequently diagnosed class of congenital myopathies. Malignant hyperthermia susceptibility and central core disease are autosomal dominant or de novo RYR1 disorder, whereas multiminicore, congenital fiber type disproportion and centronuclear myopathy are autosomal recessive RYR1 disorders. The presence of ptosis, ophthalmoparesis, facial, and proximal muscles weakness, with the presence of dusty cores and multiple internal nuclei on muscle biopsy are clues to the diagnosis. We describe an 18-year-old male, who presented with early infantile onset ptosis, ophthalmoplegia, myopathic facies, hanging lower jaw, and proximal muscle weakness confirmed as an RYR1 -related congenital centronuclear myopathy on genetic analysis and muscle biopsy.