Human epidermal growth factor receptor 2/neu expression in urothelial carcinomas.

Introduction: Urothelial carcinomas of the bladder are more common in males, making them the sixth-most common cancer in men and the tenth-most common cancer overall, worldwide. Current guidelines do not recommend routine testing for human epidermal growth factor receptor (HER2/neu) expression on the biopsy specimens of patients with urothelial carcinoma. This study was aimed at determining the expression pattern of HER2/neu and its usefulness in muscle-invasive and nonmuscle-invasive urothelial carcinoma. Methods: HER2/neu expression was assessed in 89 specimens of urothelial cancer by immunohistochemistry (IHC), and equivocal cases were subjected to fluorescent in situ hybridization (FISH). Results: On IHC for HER2/neu, 17.9% (7/39) of the muscle-invasive bladder cancers (MIBCs) showed a 3+ expression, whereas 22% (11/50) of the non-muscle invasive cancers were positive with a score of 3+. A significant correlation between HER2/neu status and muscle invasion could not be established in the current study (P = 0.74, Fisher's exact test). Three cases of muscle-invasive (7.7%) and 2 cases (4%) among nonmuscle invasive cancers showed equivocal expression. All the cases with equivocal (2+) expression on IHC were subjected to FISH and none showed gene amplification on hybridization and were considered as negative. Conclusion: Overexpression of HER-2/neu was seen in 17.9% of MIBCs and 22% of non-MIBCs. There are no norms for routine testing of HER2/neu expression in the biopsy specimens of urothelial carcinoma. There is an unmet need to establish guidelines for HER2/neu scoring, similar to that for breast and gastric cancers, to determine the proportion of positive cases and help in identification of those who may benefit from targeted therapies.

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. METHODS: Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. RESULTS: Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. CONCLUSIONS: Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Primary amelanotic malignant melanoma masquerading as adenocarcinoma prostate - A pathological dilemma.

A rare disease at an aberrant location can mimic a usual presentation of another disease. We report a case of primary amelanotic malignant melanoma of the prostate with clinical and histological characteristics that closely mimic poorly differentiated adenocarcinoma prostate.

Pediatric onset lupus nephritis in western India-is it different from the rest of the country?

AIM: To determine the clinicopathological characteristics and outcomes of children diagnosed with lupus nephritis in a tertiary hospital in western Rajasthan and compare it with the data available from other parts of India. MATERIAL AND METHODS: A retrospective review of children presenting to a tertiary care center in western Rajasthan, India, with a diagnosis of pediatric Systemic Lupus Erythematosus (p SLE), between July 2017 and July 2020 was done. Comparisons of pediatric lupus in western India to other parts of country were done. RESULTS: 19 children with SLE with Renal involvement were enrolled and followed up. The median age at presentation was 15 years (IQR-16-9.5) (73% females). 8/19 (42%) children presented with AKI, of which 62% children presented as rapidly progressive renal failure. Six (37.5%) patients required dialysis at presentation. 84.21% of children were evaluated with renal biopsy, 16 biopsies were done in 19 children, among which class II, III, and IV lupus nephritis were reported in 21%,42%, and 35% respectively(4 crescentic). Antiphospholipid antibodies were positive in 8/15(53%), children which is much higher than a reported incidence of 30% in other Indian studies. Ten patients (52%) had neurological involvement, with seizures being the most common form of presentation (60%). Seven patients (36%) developed hepatitis. We noted many uncommon presentations in the small group like Autoimmune Pancreatitis, Mononeuritis multiplex, and peripheral digital gangrene. Cyclophosphamide was used in 10 out of 19 patients for inducing remission with class 3 and 4 nephritis and MMF in 8 children. 55% patients attained remission (after completing induction), of which 4 relapsed during the follow up. Four patients were lost to follow-up. A total of 27% patients died and 10% patients developed end stage renal failure. It was seen that those who died had more cardiac and neurological involvement at presentation, higher grade of proteinuria, lower GFR, and need for dialysis at admission. CONCLUSION: We found a more severe form of clinical manifestation in pediatric SLE patients at the time of the first presentation in the form of severe renal and extrarenal manifestation compared to other parts of the country.

Pilomatricoma with florid osseous metaplasia: A common tumor with rare histopathological finding.

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a common benign skin adnexal tumor with differentiation toward hair cortex cells, commonly seen in head and neck region of children. It is usually solitary. Herein, we present a rare case of pilomatricoma with extensive osseous metaplasia as a thigh swelling in an adult female, considered clinically to be a sebaceous cyst. Florid osseous metaplasia is extremely rare in cases of pilomatricoma. To date, fewer than 10 cases of pilomatricoma with extensive osseous metaplasia at different sites have been reported in the English literature.

Pseudolinear C4d deposits in a hereditary glomerulopathy caused by a rare NC1 collagen-4-alpha-5 missense mutation: a "new disease entity"?

C4d positive glomerulopathies with pseudolinear capillary wall deposits caused by basement membrane (GBM) remodeling have sporadically been reported in renal transplants. Here we describe the case of a hypertensive 60 year-old male with a 5 month history of nephrotic range proteinuria in the setting of normal serum creatinine, complement and ANA levels. Work-up showed MGUS (IgG/kappa restricted). A diagnostic renal biopsy to search for monoclonal gammopathy of renal significance demonstrated thickened glomerular capillary walls with strong pseudolinear complement factor C4d deposits by immunofluorescence microscopy (IF); all other IF studies including stains for Col4A3 were unrevealing with only minor abnormalities seen for Col4A5. The strong and unusual C4d staining of undetermined direct diagnostic significance triggered additional electron microscopic studies uncovering marked structural GBM changes suggestive of a hereditary nephropathy. Further genetic testing revealed a very rare X-linked single missense mutation in the NC1 domain of Col4A5 (exon 51) with a single amino acid substitution (COL4A5 p.A1581S) that has thus far not been reported in hereditary nephropathies. Our case provides further support for pseudolinear glomerular C4d deposits as general markers of GBM remodeling, in our case an unexpected hereditary nephropathy in an older male. Pseudolinear C4d: a general signpost for architectural GBM disturbance and a stimulus for in-depth studies including electron microscopy.

Childhood macrophagic myofasciitis: A series from the Indian subcontinent.

INTRODUCTION: Macrophagic myofasciitis (MMF) is a rare disorder, reported mainly in European adults, with occasional childhood cases. We report a series of 6 patients with pediatric MMF from the Indian subcontinent. METHODS: Clinical details, creatine kinase levels, and results of electromyography are described for patients diagnosed with MMF. Fresh-frozen and formalin-fixed muscle biopsies were evaluated by hematoxylin-eosin staining, histochemistry, immunohistochemistry, and electron microscopy. RESULTS: Six of 2,218 muscle biopsies were diagnosed as MMF; patient charts were reviewed. The 6 patients were all children; all presented with hypotonia and/or motor delay. Mean age at diagnosis was 16.2 months. There were 4 boys and 2 girls. All had a history of hepatitis B vaccination. Histopathology revealed infiltration by sheets of large periodic acid-Schiff stain-positive histiocytes. Ultrastructural examination demonstrated needle-shaped crystals within histiocytes. One patient had a co-existent neuromuscular disorder, merosin-deficient congenital muscular dystrophy. CONCLUSIONS: MMF is a rare inflammatory myopathy that should be considered in the differential diagnosis of congenital myopathies in children. Muscle Nerve 56: 71-77, 2017.

Intracranial Aspergillosis in an Immunocompetent Young Woman.

Intracranial aspergillosis (ICA) is very rare in the immunocompetent individuals, usually misdiagnosed as a tumor or an abscess. A high index of clinical suspicion is required in patients who present with focal neurological deficits, headache, or seizures. We report the case of a 25-year-old immunocompetent female, who presented with a 15-month history of headache, seizures, left-sided proptosis and ophthalmoplegia, and right hemiparesis. Recovery from the symptoms and decrease in the lesion size seen on the radiological assessment were achieved through two decompressive craniotomies followed by prolonged combined systemic antifungal therapies. Although the initial neuroimaging suggested a mitotic pathology, the surgical sample confirmed ICA. Now the patient is on single antifungal therapy (Tab. voriconazole, 200 mg twice daily) and doing her daily activities, but with a reduced intelligent quotient. We report a challenging case of ICA where multiple courses of combined antifungal therapies and repeat surgeries paved the way for a good prognosis.

WNT-activated medulloblastoma with melanotic and myogenic differentiation: Report of a rare case.

Medulloblastoma (MB) with melanotic and myogenic differentiation, previously known as melanotic medullomyoblastoma, is an extremely rare histological variant of MB showing melanocytic as well as skeletal muscle differentiation. Only 10 cases of this rare tumor have been reported in the literature to date. We report this case of a 2-year-old male child who presented with a midline cerebellar mass, which on histopathological examination showed classic MB intermixed with cells containing melanin pigment, along with rhabdomyoblasts, spindle cells and occasional strap cells, which corresponded to WNT subgroup on molecular classification. The cell of origin of this MB variant is likely to be neural crest-derived stem cells which are capable of multilineage differentiation. Significant findings from previous reports and important differential diagnoses are discussed. Documentation of these tumors is important to characterize the clinical behaviour and to identify distinct genetic features, if any.

Utility of DOG1 Immunomarker in Fine Needle Aspirates of Gastrointestinal Stromal Tumor.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. DOG1 is a sensitive and specific immunohistochemical marker for the diagnosis of GIST. To date, no study has reported the utility of DOG1 immunocytochemistry on aspirate smears. METHODS: Aspirates with a cytological diagnosis of GIST were retrieved. DOG1 immunocytochemistry was performed on aspirates with adequate material. RESULTS: 23 cases were included (11 primary, 2 recurrent, 10 metastatic). Primary tumors were most frequently located in the stomach; most metastatic tumors were in the liver. Tumor cells were arranged in cohesive clusters with high cellularity. Cells were spindled, had a low N:C ratio, and a moderate amount of cytoplasm, which was elongated and tapering. Characteristic nuclear features included elongated nuclei with blunt or tapering ends, fine chromatin, mild anisonucleosis, and longitudinal grooves. The mitotic count was low, including in metastatic tumors. DOG1 immunopositivity was noted in 57% of the cases examined. Histopathology was available in 5 cases, all diagnosed as GIST. CONCLUSION: Cytology is a sensitive investigative modality for the preoperative diagnosis and confirmation of metastasis of GISTs. In ambiguous cases, DOG1 immunocytochemistry can serve as a valuable adjunct. Cytologic assessment, however, cannot predict malignant potential of GISTs as even metastatic tumors display bland nuclear features.

Myeloid sarcoma of the breast in an aleukemic patient: a rare entity in an uncommon location.

Myeloid sarcoma (MS) is an extramedullary solid neoplasm of immature myeloid cells. These tumours usually develop in concurrence with or following acute leukemia. The breast is an uncommon site for presentation of this tumour, where it is often misdiagnosed as lymphoma or carcinoma.A 33- year-old female presented with a right breast lump in a private hospital, which was diagnosed as ductal carcinoma on lumpectomy. Subsequently she developed a lump in the left breast and a similar diagnosis of carcinoma was made on biopsy. A left mastectomy was performed. Histopathological examination revealed a tumour composed of mononuclear cells arranged in sheets and cords with round to oval vesicular nuclei and occasional prominent nucleoli. IHC for CK was very weak and focal. The tumour cells were immunonegative for ER, PR, Her2neu,epithelial membrane antigen, e-cadherin, CD3 and CD20. Diffuse immunopositivity for myeloperoxidase, CD34 and CD117 established a diagnosis of myeloid sarcoma. A histopathological review of the right breast lesion, with immunohistochemistry, also confirmed the diagnosis of myeloid sarcoma. Investigatory workup for acute myeloid leukemia, including bone marrow aspirate and biopsy and karyotypic studies, proved negative. The patient was treated with high dose cytarabine (HDAC) regimen and was disease free during the 12-month follow-up.Although extremely rare, awareness of such a presentation is crucial. This case also illustrates that careful histopathological review along with an expanded panel of immunohistochemistry is extremely important for recognizing such cases as a misdiagnosis can lead to unnecessary surgery and inappropriate therapy.

Giant cell tumour of tendon sheath with simultaneous two tendon involvement of the foot treated with excision of the tumour and reconstruction of the flexor retinaculum using tibialis posterior tendon in a paediatric patient: A rare case report.

Giant cell tumour of tendon sheath is a benign soft tissue tumour arising from the tendon sheath. The involvement of foot and ankle by such tumours is relatively rare. Children are not commonly afflicted by this condition. All such tumours are reported to arise either from a single tendon sheath or one joint. We report a case of giant cell tumour of tendon sheath in a 12-year-old child, arising simultaneously from the tendon sheaths of tibialis posterior and flexor digitorum longus tendons, as well as extending into the ankle joint. It was treated by complete excision of the mass along with the tendon sheaths with reconstruction of the flexor retinaculum. The location of the tumour, age of the patient, diffuse nature of the tumour and novel technique of reconstruction of the flexor retinaculum make this case extremely rare and the first to be reported in literature.

Pathological fracture treated with total femoral replacement in a case of chondrosarcoma involving the entire-length femoral shaft.

INTRODUCTION AND IMPORTANCE: We here present a case of chondrosarcoma of the diaphysis of the femur with extensive involvement of the length of the bone and with the pathological fracture at the mid-shaft level. Total femur replacement was done in this case with a bipolar head and repair of abductors and hip flexors to the implanted prosthesis. CASE PRESENTATION: An elderly female in her late 60s presented to the trauma department with sudden onset pain and inability to bear weight on her left lower limb following a trivial slip and fall. The Radiographs revealed a pathological spiral mid-shaft displaced fracture of the femur with an extensive mixed lesion throughout the femur. Magnetic Resonance imaging revealed involvement of more than 90% of the femur with lesion extension into the quadriceps and hamstrings. Histopathology confirmed grade-II conventional chondrosarcoma. Metastatic work-up showed no distant spread. Wide-local resection and total femur endo-prosthetic reconstruction were done. No recurrence or infection was evident at the 18-month follow-up. In elderly non-metastatic pathological fractures, limb salvage with endo-prosthetic reconstruction can be a preferred treatment. CLINICAL DISCUSSION: This case is unique in describing a rare presentation of chondrosarcoma of the diaphysis of the femur, which eventually landed in a pathological fracture. The fracture may increase the tumour's aggressiveness, but wide-margin resection should be the mainstay treatment for primary or recurrent chondrosarcoma, irrespective of pathological fracture. CONCLUSION: In well-indicated cases (no distant spread - N0M0 disease), Total Femur Replacement (TFR) is an excellent option for limb salvage in tumours with extensive involvement of the femur.

Malignant giant cell tumour of distal ulna.

Giant cell tumour (GCT) accounts for 5% of all primary bone tumours. GCT in the distal third of ulna is quite rare. We present a case of recurrent GCT in distal third of ulna with malignant features involving tenosynovium. The case was treated by wide resection of tumour and on follow up, patient recovered well with no evidence of further recurrence. Considering the features, according to the literature reviewed, is the first case of its type.

Heterotopic Ossification After Reconstruction with Free Fibula Flap - an Ambiguous Mishap.

Heterotopic ossifications (HO) are rare, yet, well reported complications after free flap transfer. We present a case of HO that occurred within a month, and has not been previously described in the literature. This serves as a reminder that bony hard swellings proximal to the free flap within a month should raise the suspicion of HO.

Expression of Programmed Death Ligand 1 [PD-L1] and Mismatch Repair Status in Squamous Cell Carcinomas of Cervix.

Background and Objectives: To assess mismatch repair (MMR) status and programmed death-ligand 1 (PD-L1) expression in squamous cell carcinomas of the cervix and their association with clinicopathologic parameters. Material and Methods: Expression of PD-L1 and MMR status (MSH2, MSH6, MLH1, and PMS2) was assessed on 50 cases of SCCs of the cervix by immunohistochemistry. Results: 80% of tumor cells and 84% of tumor-infiltrating lymphocytes showed PD-L1 expression. 80% of cases had a combined positive score (CPS) of > 1, whereas 20% had a CPS of < 1. 94% of cases showed pMMR proteins, while 6% showed dMMR. 94% of the SCCs were HPV associated, and 6% were HPV-independent. All HPV-independent SCCs of the cervix showed PD-L1 expression, and all HPV-associated SCCs showed MMR deficiency. Between PD-L1 expression in the tumor and the grade of the tumor, a statistically significant association was noted (p = 0.022). All MMR-deficient SCCs were HPV-independent. Conclusion: This research highlighted the HPV association in cervical SCCs in the Indian population. Most of the cervical SCCs were HPV-associated. Furthermore, most of the HPV-associated SCCs were MMR stable. This study found no significant association between MMR status and PD-L1 expression in cervical SCCs.

Renal Squamous Cell Carcinoma Presenting With Renohepatic Fistula: A Rare Amalgam.

Background: Primary squamous cell carcinoma (SCC) of the kidney, a rare malignancy that accounts for less than 1% of all urinary tract malignancies, is usually diagnosed in late stages because of the lack of characteristic clinical and imaging features and aggressive behavior. Case Report: A 66-year-old male presented with complaints of right flank pain. Imaging suggested the differential diagnoses of xanthogranulomatous pyelonephritis or renal malignancy extending into segment VI of the liver. Right subcapsular nephrectomy was performed, and nonbilious fluid from the liver cavitary lesions was drained. Histopathologic examination showed that the lesion was a renal SCC with contiguous malignant infiltration of the liver that led to a renohepatic fistula. Conclusion: Renal SCC is a rare high-grade neoplasm and can present in an unusual form with a poor prognosis.

Secretory carcinoma of parotid gland masquerading as acinic cell carcinoma on cytology: Case report and review of literature.

Secretory carcinoma is a relatively recently discovered low-grade salivary gland carcinoma with morphological similarities to its breast counterpart. The histopathological features of this entity are well established; however, the cytomorphological features are not well evaluated, leading to diagnostic challenges and pitfalls. We report a case of secretory carcinoma (SC) of the parotid gland, which was misdiagnosed as acinic cell carcinoma (ACC) on fine-needle aspiration cytology, to describe the cytological features.

Pelvic Synovial Sarcoma Clinically Masquerading as an Ovarian Malignancy.

Background: Synovial sarcoma, a malignant mesenchymal tumor, commonly involves the extremities and is rarely found in the pelvis. Cytology with a biphasic pattern can suggest the diagnosis of synovial sarcoma. Case Report: A 32-year-old female presented with complaints of abdominal distension. She was initially evaluated in another hospital where she underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the abdominal mass. The mass was diagnosed as ovarian adenocarcinoma, and the patient underwent 3 cycles of chemotherapy. After 3 months, she was referred to our institute for surgical excision of the mass. Contrast-enhanced computed tomography of the abdomen suggested a well-circumscribed, heterogeneous, solid-cystic mass in the left adnexal region measuring 13.9 × 10 × 9.1 cm and compressing the adjacent structures. No previous radiologic investigations were available. We reviewed the FNAC slide from the outside hospital and made a preliminary diagnosis of biphasic synovial sarcoma. The patient underwent debulking surgery consisting of panhysterectomy with excision of the pelvic mass. Microscopic examination of the pelvic mass showed a biphasic tumor composed of epithelial and mesenchymal components, suggestive of synovial sarcoma. The immunohistochemistry profile supported the morphologic diagnosis. Bilateral ovaries were unremarkable. The patient received 4 cycles of adjuvant chemotherapy and is presently asymptomatic. Conclusion: Although primary pelvic synovial sarcoma is a rare occurrence, this case illustrates that synovial sarcoma can be diagnosed or at least suspected on FNAC. Because of the importance of adjuvant chemotherapy, synovial sarcoma must be high on the list of differential diagnoses of high-grade intra-abdominal masses.

Malignant rhabdoid tumour of liver: Conundrum on ascitic fluid.

Ascitic fluid analysis is an important tool for diagnosis and staging. Cytological analysis is routinely done as a part of workup for ascites. This is challenging in paediatric malignancies where multiple differentials need to be considered at times with limited cellularity. We present a case of malignant rhabdoid tumour of liver in a young child presenting with abdominal lump and ascites. The diagnosis was offered on ascitic fluid cytology based on cytomorphology, supporting immunohistochemistry and later confirmed on biopsy. This report briefly discusses its differentials and approach to diagnosis.