Mismatch repair protein deficiency assessed by immunohistochemistry in sporadic colorectal carcinoma.

Context: Globally, colorectal carcinoma (CRC) ranks the third most commonly diagnosed malignant disease, one of the leading causes of cancer deaths. Aims: To study the spectrum of clinicopathological characteristics of sporadic colorectal carcinoma and to assess mismatch repair gene deficiency by the expression pattern of the proteins assessed by immunohistochemistry. Setting and Design: Observational study conducted in a tertiary care hospital in West Bengal. Materials and Methods: Fifty-two surgically resected specimens of CRC received from January 2018 to May 2019 were studied for clinical, morphological, MSI status. Statistical Analysis Used: IBM SPSS 23. Results: A total of 50% of the cases belonged to younger and 50% to the older population, with male predominance being 53.8%. The most common histologic type was adenocarcinoma (88.5%). The majority was found to be well-differentiated carcinoma (50%). The majority cases were of the T3 stage accounting to 38.5%. A total of 24 out of 52 cases (46.15%) had an absent expression of at least one mismatch repair (MMR) protein. A significant correlation was found between the young age group and microsatellite instability (MSI) with a P value of 0.001. A significant association was found between MSI and tumor differentiation with P value of 0.018. A significant association was found between MSH6 and histological type with P value of 0.012. A significant association was found between MSI and tumor stage with P value of 0.032. Conclusions: This study shows a significantly higher number of sporadic colon cancers involving the young age group, and younger cases showed significant association with MSI. This alarming trend needs validation by studies involving larger populations and can be helpful prognostically as well as in formulating chemotherapeutic regimens.

Utility of cell block to detect malignancy in fluid cytology: Adjunct or necessity?

AIM OF THE STUDY: Cell block (CB) technique when supplemented with conventional smear, provides increased cellularity, preservation of architectural pattern with excellent morphology, and a clear background. We compare the utility of CB technique compared to conventional smear in detection of malignancy in serous effusions. MATERIALS AND METHODS: An institution-based observational and analytical study was carried out over 1 year on 50 patients with effusions. The residual amount of centrifuged deposit after preparation of conventional smear was mixed with 10% alcohol-formalin solution, and CBs were prepared. Calretinin and cytokeratin 5 were used for reactive mesothelial cells and Wilms tumor 1, thyroid transcription factor 1, CDX2, and estrogen receptor were used to confirm the adenocarcinoma cells. RESULTS: Maximum patients belonged to the age group of 61-70 years. Male:female ratio 1:1.17. Most common cause of malignant peritoneal effusion was due to ovarian malignancies in females and adenocarcinoma of stomach in males while, in case of pleural effusion, it was breast carcinoma in females and lung carcinoma in males. Thirteen suspicious cases were subjected to immunohistochemistry (IHC). In 70% cases, CB findings were consistent with the findings of conventional smears. In 20% cases, the conventional smears were suspicious for malignancy, and malignancy was confirmed by CB technique, whereas in 10% cases, both smears and CB were suspicious for malignancy and the original nature of the lesion was confirmed by the IHC. Sensitivity and specificity of CB compared to conventional smear were 88.88% and 86.98%, respectively. CONCLUSION: CB produced significantly better results (P = 0.0271) while detecting malignant lesions and reducing suspicious results (P = 0.0226).

Etiological study of lymphadenopathy in HIV-infected patients in a tertiary care hospital.

INTRODUCTION: Human immunodeficiency virus (HIV) infection has become a global pandemic. Persistent generalized lymphadenopathy (PGL) is very common manifestation of HIV infection. Moreover, different opportunistic infections such as tuberculosis (TB) and malignancies may present with lymphadenopathy. Mycobacterium avium complex (MAC) infection is most common with cluster of differentiation (CD)4+ count ≤50 cells/µL. Fine-needle aspiration cytology (FNAC) offers a simple and effective modality for obtaining a representative sample of the material from lymph nodes, permitting cytological evaluation and other investigations. AIMS AND OBJECTIVES: The aim of this study is to find out the different etiologies of lymphadenopathy in HIV-infected patients and to establish a possible correlation with CD4+ count. MATERIALS AND METHODS: A total of 100 HIV-infected patients having significant (>1 cm) extrainguinal lymphadenopathy were studied in 1 year at the Department of Pathology by FNAC and the stains used were Leishman-Giemsa, Ziehl-Neelsen (ZN), Papanicoloau, and Gram stains. For tubercular culture, Löwenstein-Jensen (LJ) medium was used. CD4+count was done by flow cytometer. RESULT: The present study revealed four types of cytomorphological variants in lymphadenopathy cases by FNAC, which include: Reactive hyperplasia and caseation necrosis; caseation necrosis and ill-formed granuloma; well-formed granuloma without any necrosis; and non-Hodgkin lymphoma (NHL). The highest acid-fast bacilli (AFB) positivity was among the patients showing caseation necrosis. Tubercular culture in LJ media turned out as a more sensitive method for diagnosis than routine ZN staining. The 2 cases that showed well-formed epithelioid granuloma without any necrosis turned out to be histoplasmosis and cryptococcosis, respectively. In this study, we found 2 cases of NHL. The study also revealed that caseation necrosis and AFB positivity along with opportunistic infections increases with decreased CD4+ count.

Expression of COX-2 and p53 in juvenile polyposis coli and its correlation with adenomatous changes.

INTRODUCTION: Gastrointestinal polyps commonly affect the pediatric population. The commoner variety amongst these is the solitary rectal polyp. Juvenile polyposis coli (JPC) is rare, characterized by multiple polyps occurring throughout the gut. AIM: The role of cyclooxygenase-2 (COX-2) has been implicated in gastrointestinal tumorigenesis. We aimed to look at the clinicopathological spectrum of solitary vs juvenile polyposis and compare their differences in expression of COX-2 and p53. MATERIALS AND METHODS: We studied 38 polyps from eight cases of JPC, collected over the past 10 years along with 40 solitary rectal polyps (SRP). RESULTS: The size of polyps was significantly more in cases of JPC compared to SRP. Adenomatous change was observed significantly more often in JPC. COX-2 expression was also significantly higher in the JPC group compared to SRPs. All cases of JPC polyps with adenomatous change showed strong COX-2 expression. There was no significant difference in expression of p53 in the JPC and SRP groups. CONCLUSION: We observed significantly higher COX-2 expression in JPC. Establishment of the role of COX-2 in JPC will help us formulate chemopreventive therapies as an adjunct to its surgical management.

Conservative management of Beta-thalassemia major cases in the sub-division level hospital of rural West Bengal, India.

BACKGROUND: The ideal management of thalassemia involves a multidisciplinary therapeutic team approach and should be preferably done at a comprehensive thalassemia care center with all sorts of specialists and the backup of a well-equipped blood bank. However, in developing country like ours, these facilities are not available in rural set up. So, a situation where conservative therapy with regular blood transfusion is the only choice left to innumerable thalassemic children. OBJECTIVE: To evaluate the existing conservative management protocol of Beta-thalassemia major patients in the setup of a subdivision level Government Hospital of rural West Bengal, India. MATERIALS AND METHODS: The study was performed between December 2009 and December 2011. Beta-thalassemia major patients, registered in blood bank for moderate transfusion regimen, were taken in study. All the patients were screened for Transfusion Transmittable Infections at the time of registration and thereafter periodically every six months. Iron chelation therapy was given simultaneously with transfusion at a dose of 20 to 40 mg/kg/day for six days. The patients were advised to follow up with chelation therapy at home by daily infusion with a goal of maintaining serum ferritin level below 1000 ng/ml. Over this long period of study, the patients were periodically evaluated for complications. RESULTS: The average blood requirement (ml/kg/year) in 1-5 years, 6-10 years, and 11-15 years were 110, 150, and 180, respectively. Incidence of Hepatitis C Virus infection in 1-5 years and 6-10 years were 1.75% and 2.08%, respectively. It is well seen that serum ferritin level increase with ascending age as does the blood consumption. CONCLUSION: Conservative management may be the best alternative and at times the only hope for patients in developing country like ours. However, in order to decrease the disease load, steps need to be taken to introduce preventive measures.

Evaluation of the category high-grade squamous intraepithelial lesion in The Bethesda System for reporting cervical cytology.

BACKGROUND: High grade squamous intraepithelial lesion (HSIL) is a category of The Bethesda System (TBS) for reporting cervical cytology that is in vogue since the introduction of the said system in 1988 and it was not modified in 2001 modification of TBS. The term includes moderate dysplasia (CIN II), severe dysplasia (CIN III) and squamous cell carcinoma in situ. Terms like ASC-US used in TBS are being considered to be not very useful in the prediction about the possible behavior of the pathological status of the cervix. After more than 10 years of use the term HSIL also needs fresh evaluation as in this category two entities of potentially different outcome are clubbed. AIMS: The aim was to find out whether it is justified to have a term like HSIL which includes different points of the spectrum of intraepithelial pathology of cervix from moderate hyperplasia through carcinoma in situ, all having different significance. MATERIALS AND METHODS: In this study 619 cases of cervical cytology reported by TBS were evaluated by comparing them with biopsy reports of the same lesion for the assessment of the sensitivity, specificity and positive predictive value of HSIL as a category of diagnosis in TBS. RESULTS: As a category, HSIL had the diagnostic sensitivity of 96.4%, specificity of 87.5%. The positive predictive value was 96.4%. CONCLUSION: HSIL as a diagnostic category shows a very good predictive accuracy, which implies that it provides a very high probability of the accurate diagnosis collectively of all the conditions in the disease spectrum from moderate dysplasia through in situ carcinoma. Hence, HSIL was found to be a very useful diagnostic category in TBS that conveys proper message to the clinician.

Atypical fibroxanthoma: an unusual skin neoplasm in xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder related to defective deoxyribonucleic acid (DNA) repair. Various cutaneous manifestations related to ultraviolet (UV) damage characterize the clinical course. Primary malignant cutaneous neoplasms like squamous cell carcinoma, basal cell carcinoma and malignant melanoma have been reported. Atypical fibroxanthoma is a rare dermal neoplasm occurring in UV-damaged skin. We report an unusual case of atypical fibroxanthoma in a 20-year-old male with XP.

Hypopituitarism following poisonous viperbite.

A 28 years old male had the history of viperbite 3 years back. He has treated in a nearby rural hospital with snake venom antiserum along with other supportive therapy. He responded and discharged from hospital within a week. Three years later he had history of fever, drowsiness which progressed to unconsciousness. On examination he was found to have scanty body hairs, smooth, shiny skin with superficial oral ulcers. Serum hormone estimation confirmed the deficiency of gonadotrophins, thyrotrophin and corticotrophin while growth hormone failed to rise >3ng/ml after insulin intolerance test. MRI brain revealed loss of pituitary mass with positive infundibular sign and filling of sella with cerebrospinal fluid. He was managed with hormone replacement therapy and recovered gradually.

Vanishing bone disease (Gorham's disease) - a rare occurrence of unknown etiology.

A 20-year-old male patient presented with painful swelling around left elbow joint. Radiographic examination revealed osteolytic lesion with pathological fracture of lower end of humerus and upper radius. Upper end of ulna was completely absent along with bony erosion. Histopathology of the bony tissue revealed hemangioma-like lesion composed of vascular channels lined by benign endothelium replacing bone. The diagnosis of Gorham's massive osteolysis was made. Gorham's disease is a benign self-limiting condition affecting any age, may involve any part of the skeleton and is characterized by replacement of bone by hemangiomatous tissue resulting in formation of lesions exhibiting massive osteolysis, which may be to the extent of disappearance of the affected bone in radiograph. This nonhereditary case was not associated with nephropathy, which is often a coexistent condition. The case is being reported for its rarity.

Neonatal sepsis: Role of a battery of immunohematological tests in early diagnosis.

BACKGROUND AND OBJECTIVE: Worldwide, many neonates with sepsis die due to lack of early diagnosis. In this study we attempt to analyze the value of various immunological and hematological parameters, singly and in combination, for the diagnosis of neonatal sepsis, with the aim being to formulate guidelines for the early diagnosis of the condition. MATERIALS AND METHODS: In this prospective study, 62 patients having clinical suspicion of neonatal sepsis were evaluated with a battery of investigations. Neonates admitted for other causes and without clinical suspicion of sepsis were selected as controls (n=40). The tests included blood culture, hemoglobin level, total and differential blood count, absolute neutrophil count, ratio of immature to total neutrophil count (I/T ratio), micro-erythrocyte sedimentation rate (m-ESR), C-reactive protein (CRP), platelet count, serum IgM level, and plasma fibrinogen level. Patients were divided into proven cases (positive blood culture) and probable cases (negative blood culture). RESULTS: Positive blood culture was seen in 38 cases (61.3%). Raised m-ESR (>8 mm in the first hour) was seen in 63.2% of proven and 66.7% of probable cases. I/T ratio of ≥0.2 was seen in 63.2% and 58.3% of proven and probable cases, respectively. Morphological changes in neutrophils were detected in 68.4% of proven cases and 91.7% of probable cases. Positive CRP test (≥6 mg/l) was found in 84.2% of proven cases and 100% of probable cases. Raised serum IgM, leucopenia, and neutropenia were seen in a small number of patients (11%-37%). Raised fibrinogen level (>400 mg/l) was seen in patients as well as in controls. CONCLUSIONS: The four useful tests that we identified were m-ESR, I/T ratio, morphological changes in neutrophils, and CRP; and role of these tests in early diagnosis of neonatal sepis were statistically significant (P<.05). The most sensitive test was CRP (84%) and the most specific test was m-ESR (94%). A combination of three or all of these four tests was highly specific (95%-100%).

Conjunctival biopsies and ophthalmic lesions: A histopathologic study in eastern India.

BACKGROUND: The conjunctiva is a thin and flexible mucus membrane that provides a protective barrier to the eye. Very few histopathologic studies have been conducted on conjunctival biopsies in eastern India. MATERIALS AND METHODS: 120 conjunctival biopsies from 117 patients (76 males, 41 females) received during 8 years (January 2003-December 2010) were included in this study. RESULTS: HISTOLOGIC DIAGNOSES WERE: degenerative lesions in 38 cases (31.66%), benign epithelial lesions in 23 cases (19.16%), premalignant and malignant epithelial lesions in 27 cases (22.5%), melanocytic lesions in 10 cases (8.33%), lymphoid in 7 cases (5.83%), and miscellaneous in 15 cases (12.5%). CONCLUSION: Squamous papilloma was the commonest benign tumor, whereas the commonest malignant tumor was squamous cell carcinoma. Melanocytic lesions were less prevalent compared to other/western studies.

Primary pediatric gastrointestinal lymphoma.

BACKGROUND: Primary non-Hodgkin's lymphoma (NHL) of the gastrointestinal (GI) tract is the most common extranodal lymphoma in pediatric age group. Yet, the overall incidence is very low. The rarity of the disease as well as variable clinical presentation prevents early detection when the possibility of cure exists. MATERIALS AND METHODS: We studied six cases of primary GI NHL in pediatric age group with reference to their clinical presentation, anatomic distribution and histopathologic characteristics. RESULTS: All were males except one. Intestinal obstruction was the presenting feature in 50%. Half the cases showed ileocaecal involvement, while large bowel was involved in 16%. Histology showed four cases of diffuse large B-cell lymphoma (DLBCL), one case of Burkitt lymphoma, and one Burkitt-like lymphoma. Immunohistochemistry for Tdt, CD20, CD3, CD30, bcl2, bcl6 confirmed the morphological diagnosis. CONCLUSION: Pediatric GI lymphoma commonly involves the ileocaecal region and presents with intestinal obstruction. A higher prevalence of DLBCL is found compared to other series. A high proliferative index is useful in differentiating Burkitt-like lymphoma from DLBCL.

Gauchers disease presenting with portal hypertension.

Gauchers disease is a rare lysosomal storage disorder characterized by abnormal accumulation of lipid-laden macrophages in different organs. Though hepatosplenomegaly is commonly found, symptomatic presentation with portal hypertension is rare. We report a child with liver cirrhosis and bleeding esophageal varices who was diagnosed with Gaucher's disease.

Migration and maturation pattern of fetal enteric ganglia: a study of 16 cases.

AIMS: To study the migration and developmental pattern of ganglion cells in fetuses aged 9-21 weeks, and to document whether the migration was occurring circumferentially equally in the entire axis or if there were discrepancies in different portions at the same level. SETTINGS AND DESIGN: The hypothesis regarding the pathogenesis of Hirschsprung's disease mainly revolves around two schools. One is the single gradient migration of ganglia and the other is a dual gradient migration theory. Understanding the embryological development of enteric ganglia is necessary to study the pathogenesis of intestinal innervation disorders. MATERIALS AND METHODS: We studied the development of intestinal ganglia in fetuses aged 9-21 weeks. Serial longitudinal sections from the colon were studied, the first one including the squamo-columnar junction, for the presence and the nature of ganglion cells with Hematoxylin and Eosin, and neurone-specific enolase immunostaining. Transverse sections from proximal gut were studied in a similar fashion. Thus, we evaluated the migration pattern as well as the nature of ganglia in the fetuses. We also measured the length of distal aganglionic segment in these growing fetuses. RESULTS: We noted that ganglion cells appear first in the myenteric plexus followed by deep and superficial submucous plexus. We also found evidences in favor of dual migration theory, and the distal aganglionic segment varies around the circumference of the rectal wall. CONCLUSIONS: We got evidences in support of a dual migration pattern of intestinal ganglion cells. The level of distal aganglionic segments when measured from squamo-columnar junction varied with the age of gestation and the length was incongruous. The description of distal aganglionic segment may help surgeons while taking biopsies or during operative procedures.

Primary pulmonary neoplasms in children: A report of five cases.

Primary pulmonary neoplasms are uncommon in children and represent a wide spectrum of pathology from benign to malignant. They are quite different in their histopathologic distribution from that of adults. This study was done to analyze the histopathologic spectrum of primary lung tumors in children. All the resected specimens of lung in children over a period of 5 years were studied and only the cases of primary pulmonary neoplasms were further analyzed. There were two cases of inflammatory myofibroblastic tumor. The patients were boys aged 10 and 12 years, respectively. One case of bronchial carcinoid was diagnosed in a boy of 12 years. There were one case each of pleuropulmonary blastoma (PPB) in a girl of 9 years and pulmonary blastoma (PB) in a girl of 2 years of age. In our study, the two cases of inflammatory myofibroblastic tumor had excellent prognosis. However, the cases of PPB and PB were both associated with poor clinical outcome, whereas the case of bronchial carcinoid has been doing well on follow-up.

A study on expression pattern of cyclooxygenase-2 in carcinoma of cervix.

OBJECTIVE: The purpose of the present study was to determine the differential expression pattern of cyclooxygenase-2 (COX-2) in patients of carcinoma of uterine cervix and its correlation with tumor differentiation and lymphovascular invasion. MATERIALS AND METHODS: Seventy (70) cases of cervical carcinoma were included (20 in-situ, 42 invasive squamous cell, and 8 cases of adenocarcinoma). Formalin-fixed paraffin-embedded tissue sections were stained by Hematoxylin and Eosin. Immunohistochemistry for COX-2 were performed on these blocks. RESULTS: A higher expression of COX-2 was seen in invasive squamous cell carcinoma than in in-situ carcinoma (P = 0.002). Five out of eight cases of adenocarcinoma showed strong positivity for COX-2 antibody. Among the histopathological correlates, tumor differentiation did not show a positive correlation (P = 0.717), while lymphovascular invasion was associated with positive staining in majority of the cases (P = 0.001). CONCLUSION: Expression of COX-2 is more in cases of invasive than in in-situ carcinoma. Adenocarcinomas showed a strong expression of COX-2. A positive association of COX-2 expression and the presence of lymphovascular emboli were found in the present study. COX-2 inhibitors need to be studied as a therapeutic adjunct for the treatment of carcinoma cervix.

Distinction of phyllodes tumor from fibroadenoma: Cytologists' perspective.

BACKGROUND: Fibroadenomas and phyllodes tumors may have similar cytological appearances. However, a detailed study of cytomorphology of stromal elements may be helpful in differentiation. AIM: To evaluate the cytological features of phyllodes tumor in our study with special reference to features that can help distinguishing it from fibroadenoma. MATERIALS AND METHODS: The archival materials of our hospital were searched from January 2006 to January 2009 for histopathologically-diagnosed cases of phyllodes tumor. The cases in which previous cytopathology smears were available were included in the study. The cytomorphology of 10 such cases were compared with 25 cytologically-diagnosed and histopathologically-confirmed cases of fibroadenoma. RESULTS: The size, cellularity of stromal fragments, and the proportion of spindle cells in the background are important features in such differentiation.

Neurofibroma of kidney: an uncommon neoplasm and diagnostic dilemma with solitary fibrous tumor.

Neurofibroma of kidney is an extremely rare tumor. To our knowledge, only five such cases have been reported worldwide till date. Here, we report a solitary neurofibroma of right kidney in a 54-year-old woman. Radiological investigations (ultrasonography and computed tomography) detected a solid mass in the upper pole of right kidney and clinicoradiologically renal cell carcinoma was suspected. A radical nephrectomy was performed under diagnosis of cancer. Microscopically, tumor consisted of benign spindle-shaped cells accompanied by fibrous tissue. Differential diagnoses of neurofibroma and solitary fibrous tumor (SFT) were made on morphological features. Immunohistochemically, the tumor cells were positive for S-100 protein, but negative for CD34 and CD99. Thus, a diagnosis of neurofibroma was established.

Massive scapular metastasis as a presenting feature of carcinoma of the lip.

Carcinoma of the lip is a slow-growing locally-advanced disease with low metastatic potential. Distant skeletal metastasis is reported very rarely and the vertebral column is the most common site. A 58-year-old male smoker presented with pain and massive swelling of the left scapula for six months. He also noticed a slowly-growing painful ulcerated lesion on the outer aspect of the right lower lip for last two years. Biopsy from the lip ulcer, as well as cytologic smears from the scapular mass, revealed features of squamous cell carcinoma. Though no neck node was detected, patient was found to have extensive skeletal metastasis on whole body bone scan. It is rare as well as clinically appealing to have such disfiguring symptomatic massive scapular metastasis as the chief presenting feature in carcinoma of the lip.