Background: An alarming increase in incidence of high-risk human papillomavirus (HPV) positive tumors in head and neck squamous cell carcinoma (HNSCC) by 25% and 70% in oropharyngeal HNSCC cannot be ignored. The early oncogenes of HPV, E6, and E7 play a key role in carcinogenesis. HPV associated tumors have a better clinical outcome and a favorable prognosis. The p16 expression has high concordance with other methods of HPV detection, ascertaining p16 as a surrogate marker for HPV. Objective: To assess the immunohistochemical expression of p16 in oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) with and without coexistent OSF as a marker for high-risk HPV detection. Materials and Methods: Tissue blocks of 70 cases including normal, OSF, OSCC with and without OSF were subjected to IHC staining with a p16^INK4A monoclonal antibody. (Biogenex, San Roman). The p16 expression was noted according to percent positivity and pattern. The data were tabulated, statistically analyzed using the Chi-square test and the P value was assessed. Results: The percentage of p16 positive cells raised from normal to OSF to OSCC with and without OSF. In addition, a shift from nuclear to cytoplasmic expression from normal to OSCC was noted with a statistical significance (P < 0.001). However, no statistical significance was established with any clinicopathologic parameters except age (P = 0.012) and habits (P= 0.023). Conclusion: The presence of HPV using p16 was not detected in OSF but was positive in OSCC. Altered pattern of expression from normal to OSF to OSCC indicates promising use of p16 as a diagnostic marker.

Background: In recent years, high-throughput omics technologies have been widely used globally to identify potential biomarkers and therapeutic targets in various cancers. However, apart from large consortiums such as The Cancer Genome Atlas, limited attempts have been made to mine existing datasets pertaining to cancers. Methods and Results: In the current study, we used an omics data analysis approach wherein publicly available protein expression data were integrated to identify functionally important proteins that revealed consistent dysregulated expression in head and neck squamous cell carcinomas. Our analysis revealed members of the integrin family of proteins to be consistently altered in expression across disparate datasets. Additionally, through association evidence and network analysis, we also identified members of the laminin family to be significantly altered in head and neck cancers. Members of both integrin and laminin families are known to be involved in cell-extracellular matrix adhesion and have been implicated in tumor metastatic processes in several cancers. To this end, we carried out immunohistochemical analyses to validate the findings in a cohort (n = 50) of oral cancer cases. Laminin-111 expression (composed of LAMA1, LAMB1, and LAMC1) was found to correlate with cell differentiation in oral cancer, showing a gradual decrease from well differentiated to poorly differentiated cases. Conclusion: This study serves as a proof-of-principle for the mining of multiple omics datasets coupled with selection of functionally important group of molecules to provide novel insights into tumorigenesis and cancer progression.

Background: Oral submucous fibrosis (OSMF), a well-recognized oral potentially malignant disorder, results due to increased collagen production and reduced collagen degradation. Aims and Objectives: To qualitatively compare the staining properties of collagen in OSMF using two special stains based on their birefringent property using polarizing microscopy. The study also assessed the distribution and orientation of collagen fibers in different grades of OSMF. Materials and Methods: A total of 73 subjects with different clinical and histopathological staging of OSMF comprised the study population. Histopathological examination was done using hematoxylin and eosin stain, Van Gieson and picrosirius red. Collagen fibers were analyzed for polarization colors, distribution, and orientation. Results: Picrosirius red stained both thick and thin collagen fibers. Irrespective of the histopathological grades reddish orange and yellowish orange were the most predominant colors. Parallel arrangement of fibers was observed when stained with Van Gieson but picrosirius red stained sections showed a majority of parallel type I fibers with perpendicular type III fibers which increased with advancement in the histopathological grade. Yellowish orange and greenish yellow fibers were predominant in the lamina propria, while reddish orange fibers were predominant in the submucosa. Conclusion: Picrosirius red was found to be a better stain. Histopathological grading and polarization colors showed no association with each other. Collagen fibers were more thickly and tightly packed in the submucosa indicating that the process of fibrosis began there. The increase in perpendicular type III fibers with advancing histopathological grades suggested their role in fibrosis.

Context: Atypia of undetermined significance/Follicular lesion of undetermined significance [AUS/FLUS] is a heterogeneous category with a wide range of risk of malignancy [ROM] reported in the literature. The Bethesda system for reporting thyroid cytopathology [TBSRTC], 2017 has recommended subcategorization of AUS/FLUS. Aims: To evaluate the ROM in thyroid nodules categorized as AUS/FLUS, as well as separate ROM for each of the five subcategories. Settings and Design: Retrospective analytic study. Methods and Materials: A retrospective audit was conducted for all thyroid fine-needle aspiration cytology (FNAC) from January 2013 to December 2017. Slides for cases with follow-up histopathology were reviewed, classified into the five recommended subcategories, and differential ROM was calculated. Statistical Analysis Used: z test for comparison of proportions was done to evaluate the difference in ROM among different subcategories of AUS/FLUS. The P value of less than 0.05 was taken as statistically significant. Results: Total number of thyroid FNACs reported was 1,630, of which 122 were AUS/FLUS (7.5%). Histopathology was available in 49 cases, out of which 18 were malignant (ROM = 36.7%). The risk of malignancy (ROM) for nodules with architectural and cytologic atypia was higher (43.8%) than ROM for nodules with only architectural atypia (16.7%). Conclusions: The sub-classification of AUS/FLUS into subcategories as recommended by TBSRTC, 2017 may better stratify the malignancy risk and guide future management guidelines.

Context: C-Cbl is an important negative regulator of the cell signaling that acts as an adaptor protein and E3 ubiquitin ligase. The role of c-Cbl in development and regulation of human cancer has aroused intensive attention. Aims: In this study, we aimed to assess the correlation between the expression of c-Cbl and clinicopathological parameters and explored the role of c-Cbl in the development and progression of GC. Settings and Design: This is a Pilot study. Methods and Materials: In total, 84 tissue samples including 44 gastric cancers (GC) and 40 matched adjacent normal tissues were collected after surgery. Then tissue microarray (TMA) and immunohistochemistry (IHC) technology were combined to detect the protein expression of c-Cbl. Statistical Analysis Used: Statistical analysis was performed using SPSS 22.0 (IBM Corporation, Armonk, NY, USA). Results: We have studied the correlation between c-Cbl expression and clinicopathological parameters. Our study showed that c-Cbl has a low expression in 61.4% (27/44) of GC tissues, and the incidence of cases was significantly higher than that in adjacent normal tissues (P < 0.0001). In addition, the correlation between c-Cbl expression and gastric carcinoma subtype (P = 0.027), histological type (P = 0.033), Borrmann classification (P = 0.009), histological differentiation (P = 0.0005), lymph node metastasis (P = 0.007), and intravascular tumor thrombus (P = 0.036) has also been revealed. Conclusions: Our results show that c-Cbl is down-regulated in GC tissues compared with normal gastric tissue, which may play an important role in the development and progression of GC.

Background: Hepatoblastoma is the most common primary hepatic malignancy in the pediatric population. Advances in pathological evaluation, imaging, risk stratification, neo-adjuvant chemotherapy, and surgery including transplantation have improved survival of these children in the western countries. However, a successful outcome in developing countries such as India with limited resources poses great challenges to the clinician and the family. Histology plays a major role in determining the prognosis of these patients. Methods: A retrospective study was done on 10 children diagnosed with hepatoblastoma between January 2010 and December 2015 in our institution. Clinical, laboratory, radiological, histopathological diagnoses, treatment, and outcome data were collected and analyzed. Results: The median age of these children at diagnosis was 11 months, and only 1 child was premature at birth. Most children were presented with abdominal distension. One child had lung metastasis at presentation. Elevated alpha fetoprotein levels were present in 90% of the children. The histological types were fetal, embryonal, macrotrabecular, and mixed epithelial-mesenchymal types. SIOPEL risk stratification was done, which showed 40% of the children to be of high risk. Three children had PRETEXT 1, 2, and 4, respectively. Conclusion: Our study is significant with respect to the information on PRETEXT staging, risk status, and histological favorability. In developing countries with limited resources and low-socioeconomic status, it is important to have a multidisciplinary team approach and tailor treatment to manage these patients effectively and improve the overall survival.

Introduction: We have aimed to evaluate the difference between the expression of p53, Ki-67, and laminin in keratoacanthoma and well-differentiated SCC (SCC) and to determine its importance in differential diagnosis. Methods: This study totally included 46 cases consisting of 23 cases with keratoacanthoma and 23 with SCC. As well as age, gender, localization, and diameter of the lesion, the expression of p53, Ki-67 and laminin was evaluated. Results: No statistically significant difference was found between KA and well-differentiated SCC in terms of diameter, age, and localization. There was a statistically significant difference between KA and well-differentiated SCC in terms of p53 and Ki-67 staining (P < 0.001). Increased expression of p53 and Ki-67 was found in well-differentiated SCC. A statistically significant correlation was present between the expression of p53 and Ki-67 in KA. A statistically significant difference was detected between KA and well-differentiated SCC in terms of laminin staining (P = 0.018). Increased laminin expression was determined in well-differentiated SCC. Conclusion: We have determined in this study that p53, Ki-67 and laminin may be used as adjuvant immunohistochemical markers in differential diagnosis of KA and well-differentiated SCC.

Context: Malignant pericardial effusions (MPCEs) is a common complication observed in advanced pulmonary adenocarcinoma. In such cases, investigating molecular alterations can have significant therapeutic implication in determining anticancer drugs. Aim: The objective was to evaluate the significance of cell block technique in the diagnosis of MPCE and further investigate the morphological and molecular profiles of MPCE in patients with pulmonary adenocarcinoma. Setting and Design: Cytopathological and molecular profiles of 19 MPCE cases in patients with pulmonary adenocarcinoma were retrospectively analyzed. The control group consisted of 14 malignant pleural effusion (MPE) cases in patients with pulmonary adenocarcinoma. Materials and Methods: Anaplastic lymphoma kinase (ALK) and tyrosine-protein kinase Met (C-MET) expression was evaluated by fluorescence in situ hybridization (FISH). Epithelial growth factor receptor (EGFR) and K-Ras (KRAS) mutations were detected by ARMS real-time polymerase chain reaction (RT-PCR). Statistical Analysis Used: Associations between MPCE and MPE were analyzed using Fisher's exact test. Results: MPCE was found to have micropapillary and solid pattern predominant with mucin secretion compared to acinar patterns, as seen in MPE. Seventeen MPCE cases (89.5%) and all MPE cases (100%) underwent molecular analysis. Mutations in EGFR and KRAS, ALK rearrangement, and C-MET amplification were observed in MPCE and MPE with statistical differences. Additionally, two MPCE cases demonstrated EGFR T790M mutation and multiple insertions at L858. Conclusions: MPCE shows micropapillary and solid cytological patterns predominant with mucin secretion. MPCE are suitable to analyze oncogenic mutations and to develop targeted therapy for patients with pulmonary adenocarcinoma. Further molecular investigations may reveal novel molecular alterations.

Introduction: Automated body fluid (BF) analysis is gradually replacing the traditional methods of cell counting in all BFs. This study was done to analyze the high-fluorescence (HF)-BF parameter generated on Sysmex XN-1000 and study its correlation with the presence of malignant cells in the body fluids. A correlation between manual and automated differential counts was also done. Materials and Methods: A total of 1985 samples including 797 ascitic fluids (AF), 532 pleural fluids (PF), and 656 cerebrospinal fluids (CSF) were run on Sysmex XN-1000 in BF mode and cytopathology was available for 924 BFs including 389 AF, 379 PF, and 156 CSF. Both manual and automated methods were used for cell differential and cell morphology. Results: Of the 924 samples with corresponding cytopathology, malignancy was found in 59 samples. The HF-BF%/100 WBCs (24.8 ± 72.5) and HF-BF#/μL (329.86 ± 932.35) for malignant BF samples were found to be significantly higher than the nonmalignant samples (4.41 ± 8.1) and (19.57 ± 61.91), respectively. Receiver–operator-characteristic curve cutoffs for all BF for percentage and absolute HF-BF were 2.85%/100 WBCs and >12/μL. A good correlation was found between the manual and automated WBC differential counts in all fluids except CSF with total count <5/μL. Conclusions: BFs can be reliably analyzed on automated analyzers. HF-BF parameter is helpful in identifying malignant samples but cannot be totally relied upon. If HF-BF%/# are above the lab-generated cutoffs, microscopy should be done. A complete validation study on HF-BF parameter in BF mode is desired to set the standards for the analysis of serious effusions.

Objectives: To study the role of serum procalcitonin as a diagnostic biomarker in sepsis and to compare it with other sepsis markers (IL-6, CRP) in patients of suspected sepsis. Materials and Methods: A total of 80 patients were included in this study from ICU and each patient was investigated for serum Procalcitonin, Interleukin-6 and C-reactive protein levels by ELISA along with blood cultures by BacT/Alert system. Result: Procalcitonin along with CRP is a better diagnostic tool for sepsis.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and is a leading cause of cancer-related death worldwide. It has a very aggressive clinical course, with a mean survival rate of much less than a year if left untreated. Here, we present a case of a 68-year-old male with progressively enlarging painful right facial swelling, involving the ramus and condyle of mandible on contrast-enhanced computed tomography mimicking an osteosarcoma. Eventually, the final diagnosis of HCC metastatic to the right parotid gland was made. We report a case of a rare metastasis of HCC to the parotid gland. Furthermore, the present case demonstrates the importance of tissue biopsy and immunohistochemistry for obtaining an accurate final diagnosis.

The follicular variant of peripheral T-cell lymphoma, not otherwise specified, is very rare. Primary epiglottic follicular variant of peripheral T-cell lymphoma is extremely rare in clinical practice. Here, we report the first case of a follicular variant of peripheral T-cell lymphoma not otherwise specified in a 44-year-old Chinese man, who presented with a tumor in the middle of the epiglottis tongue surface. Microscopically, the tumor had a vague nodular growth pattern and the morphology of the nodules was different from each other at low power. Atypical lymphoid cells were medium to large in size and had round nuclei, with an irregular nuclear membrane, distinct nucleoli, and rapid mitotic activity. Plasma cells were found surrounding the nodules. The tumor cells were positive for follicular helper T-cell markers (CD10, PD-1, CXCL13, and BCL-6). The EBER was negative by in situ hybridization. Polymerase chain reaction-based analysis showed monoclonal rearrangements of TCRβ, TCRγ, and polyclonal rearrangements of IgH, IgK, and IgL. The clinical and imaging features and the prognostic factors of FV PTCL-NOS remain poorly understood. Thus, investigation of more cases and longer follow-up is necessary to understand the disease and to identify the best treatment to improve prognosis.

Endocarditis caused by Mycobacterium abscessus is rare and often missed without appropriate blood cultures. It does not respond to standard antitubercular treatment and is also resistant to many other antibiotics. The course of the disease may be indolent and often results in a fatal outcome. Accurate identification and sensitivity, combination therapy, and prolonged duration of antibiotics are, therefore, important for a successful outcome.

Sympathetic ophthalmia (SO) is a rare bilateral diffuse granulomatous panuveitis that occurs in few days to several years after penetrating injury. This intraocular inflammation can occur in any age group without a sex predilection. Pathology and immunohistochemistry-supported evidence is important to know the disease in a better way. We present a case of a 24-year-old female with clinical diagnosis of SO with an atypical past history of chicken pox in that eye and residual corneal opacity.

Pleuropulmonary blastoma (PPB) is a rare aggressive intrathoracic tumor which is believed to originate from embryonic uncommitted lung mesenchymal cells, which are important for developing the lung. Type I PPB is cystic, type II is cystic and solid, while type III is predominantly solid. Diagnosing type 1 PPB is a challenge for both radiologists as well as pathologists. Owing to its purely cystic nature, type I PPB it is often mistaken for unrelated entities such as congenital pulmonary airway malformation and congenital lobar emphysema which delays surgical intervention. Here, we report two such cases presenting clinically and radiologically as congenital pulmonary airway malformation. On histology, a final diagnosis of type I pleuropulmonay blastoma was made. Thereafter, chemotherapy was administered following complete surgical excision.

The estimated incidence of primary cardiac tumors is extremely rare. Among it, cardiac myxoma represents the most common benign cardiac tumor constituting about 80% of cases. We are presenting a 30–year-old female with large left atrial myxoma. She was presented with severe dyspnea, palpitations, and systolic murmurs. On 2D echocardiography, left atrial mass obstructing mitral flow was noted. On cardiac magnetic resonance imaging, a single, large, mobile pedunculated mass lesion in left atrium attached to inferior interatrial septum with heterogeneous enhancement was noted, which was likely represented to be myxoma. The mass was surgically excised and valve repairing was done. We received large, solid, lobulated, gray white, soft-to-firm mass measuring 4.5 × 4.1 × 2.5 cm, and on microscopy showed cardiac myxoma with cartilaginous differentiation. We are presenting this case for its clinical, imaging, and uncommon histological features.

Myeloid sarcoma is an extra medullary manifestation of acute myeloid leukemia (AML). Primary involvement of the biliary tract with myeloid sarcoma presenting as obstructive jaundice without evidence of leukemia is very rare. Here we present a case of 72 year old lady, who initially presented with features of biliary obstruction and was clinically considered as cholangiocarcinoma. She was diagnosed as myeloid sarcoma involving right and left hepatic duct, common bile duct (CBD) on histopathological and immunohistochemistry (IHC) examination after surgical resection. Since she did not show evidence of leukemia on peripheral blood and bone marrow examination treatment was deferred. However, she developed full blown picture of AML within two months and succumbed to her disease. We conclude that obstructive jaundice can be the presenting symptom in myeloid sarcoma without evidence of AML in peripheral blood and bone marrow. However, these cases have to be treated aggressively to obtain remission.

Splenic cysts are rare with an overall incidence of 0.07% in a large autopsy series and 0.5% among all the splenectomies done. The parasitic splenic cysts, usually caused by Echinococcus granulosus, account for 60% of all primary splenic cysts. The primary epithelial cysts account for 10% of all splenic cysts. We report a case of 30-year-old female presenting with left upper abdominal pain and heaviness. Computed tomography revealed a multiloculated cyst in spleen. Hydatid serology was negative. Total splenectomy was done. Histopathological evaluation was done and a diagnosis of primary epithelial splenic cyst was given.

Endolymphatic sac tumour (ELST) is a non-metastasizing low grade adenocarcinoma of endolymphatic sac origin. It is also known as Heffner tumour, low grade adenocarcinoma of endolymphatic sac origin and aggressive papillary middle ear tumour. These tumours are closely associated with Von Hippel Lindau (VHL) disease. Here we report a case of Endolymphatic sac tumour in a 63 yr old lady who presented with left sided facial palsy. Since the tumour was highly vascular and required preoperative embolization, initial clinicoradiological diagnosis was Jugulotymphanic paraganglioma. Histopathology showed features of Endolymphatic sac tumour, which was confirmed by immunohistochemistry. Since this tumour is locally aggressive low grade adenocarcinoma, the diagnosis is difficult in advanced cases where there is erosion of petrous temporal bone or the lesion shows extension into cerebellopontine angle as in our case. Since the association of this tumour with VHL disease is well established, it is important to screen all the patients of VHL disease for this lesion and also all the patients of ELST should be screened for other lesions of VHL disease to aid in early diagnosis and treatment. The case is presented here for its rarity and difficulty in initial diagnosis.

Sirenomelia is a rare congenital anomaly characterized by the presence of a median single lower appendage. The affected fetus is popularly referred to as a “Mermaid baby,” due to the uncanny resemblance to the fictious fable character. The manifestation is a result of the merger of the lower limbs with variable fusion or complete absence of bones. Sirenomelia is universally fatal due to the associated lethal anomalies involving the internal organs, which are usually part of the VACTER or VACTERL complex. However, this sirenomelia-afflicted fetus is unique in being associated with VACTERL as well as congenital hydrocephalus.

Pediatric small round cell tumors (PSRCTs) constitute a large proportion of childhood malignancies with overlapping diagnostic and clinical features but radically different therapies. Here, we report a case of 16-year-old male child presenting with diffuse abdominal and mediastinal mass, axillary lymphadenopathy, and pleural effusion. Bone marrow aspirate showed near total replacement by small round malignant cells. The bone marrow biopsy showed interstitial infiltration by malignant cells, which were CD45− CD3− CD20− MIC2+ FLI1+ and diagnosis of Ewing's sarcoma was established. In contrast, flowcytometric immunophenotyping of the bone marrow aspirate showed CD45− cells, which were CD19+ cytCD79a+ CD10+ CD81+ CD38+ HLA-DR+ CD22+ CD20− consistent with B-cell acute lymphoblastic leukemia (B-ALL). The extended immunostaining panel on bone marrow biopsy also showed positivity for cytCD79a, CD10, CD19, and BCL-2, whereas fluorescent in-situ hybridization for EWSR1 gene rearrangement was negative. Thus, a final diagnosis of CD45− FLI1+ MIC2+ B-ALL was established. Rare cases of CD45− B-ALL with immunoreactivity for MIC2 and Friend leukemia virus integration 1 (FLI1) have posed a diagnostic challenge for PSRCTs in the recent past. This case report highlights the role of multimodality approach in establishing a correct diagnosis in CD45− PSRCTs to ensure definitive therapy and better clinical outcome.

Opportunistic fungal infections occur predominantly in immunocompromised (IC) patients. Mucormycosis has the highest mortality among fungal infections. The organism is ubiquitous in its presence. The infection is commonly acquired by inhalation of fungal spores or by inoculation by direct trauma. Rhinocerebral and pulmonary mucormycosis present commonly with high mortality rates. Cutaneous mucormycosis (CM) is rarely reported and usually presents in two forms, superficial and disseminated. The superficial infection occurs commonly in immunocompetent hosts, and it can sometimes turn angioinvasive and become a fatal and very aggressive disseminated disease, especially in IC hosts. Coexistant risk factors increase the mortality rate. We report a case of posttraumatic, highly lethal, angioinvasive, and gangrenous type of CM of the arm in an IC patient. Diabetic ketoacidosis and cirrhosis due to chronic alcoholic liver disease were the risk factors.

Nocardia spp. are filamentous Gram positive bacteria that are ubiquitous soil saprophytes. The majority of nocardial infections occur in severely immunocompromised patients who are particularly susceptible to pulmonary disease and dissemination. Extrapulmonary nocardiosis is relatively common and can occur through hematogenous dissemination or a contiguous spread of necrotizing pneumonitis. Primary cutaneous and soft tissue nocardiosis can result from traumatic injury to the skin that involves contamination with soil. After skin inoculation, a superficial abscess or localized cellulitis can develop. Co-trimoxazole is the drug of choice for all types of nocardiosis. We are reporting a case of Nocardia cyriacigeorgica presenting as cellulitis followed tooth extraction.

Actinomycosis, a chronic suppurative and granulomatous infection, is caused by Actinomyces israeli. The common clinical presentations are cervicofacial, abdominal, and thoracic regions. Abdominal wall actinomycosis following pelvic or intraperitoneal involvement is known, but isolated abdominal wall involvement is extremely rare and can mimic malignancy. We report a case of primary actinomycosis of anterior abdominal wall, diagnosed on fine needle aspiration cytology (FNAC). Identifying fluffy colonies and branching swirling filaments positive for fungal and Gram stain on cytology smears aid correct diagnosis. FNAC is an effective and reliable tool for early diagnosis of actinomycosis. The treatment is centered around antibiotics, and thus it is essential to diagnose accurately and avoid unnecessary surgery.