Shilpa Jain - Academia.edu (original) (raw)

Papers by Shilpa Jain

American Journal of Clinical Pathology, 2018

Case Reports in Gastrointestinal Medicine, 2017

Disseminated toxoplasmosis is uncommon in both immunocompetent and immunocompromised hosts with g... more Disseminated toxoplasmosis is uncommon in both immunocompetent and immunocompromised hosts with gastrointestinal involvement being rarely described. We report a case of disseminated gastrointestinal toxoplasmosis in an immunocompromised man who presented with one month of diarrhea and abdominal pain. Imaging showed thickening of the ascending colon and cecum. Esophagogastroduodenoscopy and colonoscopy biopsies revealedToxoplasma gondii, confirmed by immunostain. Symptoms completely resolved following treatment with pyrimethamine, sulfadiazine, and leucovorin. This case highlights the importance of including toxoplasmosis in the differential diagnosis of any immunocompromised individual presenting with gastrointestinal symptoms.

American Journal of Clinical Pathology, 2012

Ectopic urate crystal deposition at sites other than joints, connective tissue, and kidney is ext... more Ectopic urate crystal deposition at sites other than joints, connective tissue, and kidney is extremely rare in a patient with gout. We report a case of intestinal perforation secondary to urate crystals in a pancreatic pseudocyst in a patient with concomitant gout and rheumatoid arthritis. A 52-year-old man with a medical history of coronary artery disease, pancreatitis, pancreatic pseudocyst, gout, and rheumatoid arthritis presented to the hospital with abdominal pain, nausea, vomiting, and fever. Radiology showed a 10.4 × 7.8-cm pseudocyst of the pancreas directly abutting adjacent distal transverse colon and inferior aspect of the stomach. Serum uric acid level was normal, and rheumatoid factor level was raised at this time. A resected specimen of the transverse colon and the necrotic content of the pseudocyst were received in our pathology department. Grossly, the transverse colon showed ulcerated necrotic area on the serosal surface with a tract communicating with the luminal surface. The perforation site was confirmed microscopically. Nonaqueous alcoholic eosin staining (NAES) was used on formalin-fixed tissue to preserve the water-soluble urate crystals. Positively birefringent, needle-shaped urate crystals were demonstrated in the necrotic tissue from the pseudocyst and on the serosal surface and site of perforation of the transverse colon. Urate crystals in pancreatic pseudocyst most likely lead to intestinal perforation. To our knowledge, urate crystal deposition as a possible cause of intestinal perforation in a pancreatic pseudocyst has not been reported in the literature.

International journal of clinical and experimental pathology, Jan 23, 2010

Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the m... more Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the morphology and type of tissue that they resemble, such as rhabdomyosarcoma, which resembles skeletal muscle. However, the cell of origin is unclear in numerous sarcomas. Molecular genetics analyses have not only assisted in understanding the molecular mechanism in sarcoma pathogenesis but also demonstrated new relationships within different types of sarcomas leading to a more proper classification of sarcomas. Molecular classification based on the genetic alteration divides sarcomas into two main categories: (i) sarcomas with specific genetic alterations; which can further be subclassified based on a) reciprocal translocations resulting in oncogenic fusion transcripts (e.g. EWSR1-FLI1 in Ewing sarcoma) and b) specific oncogenic mutations (e.g. KIT and PDGFRA mutations in gastrointestinal stromal tumors) and (ii) sarcomas displaying multiple, complex karyotypic abnormalities with no specif...

International journal of clinical and experimental pathology, Jan 10, 2010

Carney complex is a syndrome that may include cardiac and mucocutaneous myxomas, spotting skin pi... more Carney complex is a syndrome that may include cardiac and mucocutaneous myxomas, spotting skin pigmentation, and endocrine lesions. Many patients with Carney complex have been shown to have a stop codon mutation in the PRKAR1A gene in the 17q22-24 region. Here we present the case of a 57 year-old man with multiple skin lesions and cardiac myxomas. Histology of the skin lesions showed lentigenous melanocytic hyperplasia and cutaneous myxomas, confirming the diagnosis of Carney complex. Lesional and control normal tissue from the patient were identified and sequenced for the PRKAR1A gene. A germline missense mutation was identified at exon 1A. This is the first report of this mutation, and one of the few reported missense mutation associated with Carney complex. This finding strengthens the argument that there are alternative ways in which the protein kinase A 1-alpha subunit plays a role in tumorigenesis.

Hypertension, 2008

Reduced β-adrenoreceptor signaling is associated with increased sympathoadrenal activity in hyper... more Reduced β-adrenoreceptor signaling is associated with increased sympathoadrenal activity in hypertensive patients and animal models of hypertension. However, the mechanism that accounts for this characteristic decline in β-adrenergic signaling is unclear. In the present study, we investigated renal phosphodiesterase 4B, which metabolizes cAMP. Immunoblot analysis detected only the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive (SS) rats, and Dahl salt-resistant rats. The phosphorylated (activated) form of the protein was present at 2-fold greater levels in Dahl SS rats than in spontaneously hypertensive rats and Dahl salt-resistant rats, whereas the unphosphorylated form of the protein was reduced by approximately one half in SS animals. In accord with immunoblot data, rolipram-inhibitable cAMP hydrolyzing activity, a measure of PDE4 activity, was ≈3-fold greater in kidney cytosolic extracts from SS rats ...

Cases Journal, 2009

Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is most frequently represent... more Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is most frequently represented by the mucosa-associated lymphoid tissue type. We describe a case of a 67-year-old woman who presented with fatigue, mild dyspnea, and consolidation on chest radiograph. The diagnosis of non-Hodgkin's lymphoma was established by transbronchial biopsy, and chemotherapy was then started. The patient was treated with 6 cycles of chemotherapy. She had good response to therapy and no progression of the disease was observed during a 4-year follow-up period. The clinical, radiological and histopathological features are described. This entity has an indolent course, good response to therapy and favorable prognosis. However, despite being an incidental radiological finding in a third of cases, this disease remains highly underdiagnosed.

Cancer, 2013

Background-Androgen receptor (AR) expression in breast cancers may serve as a prognostic and pred... more Background-Androgen receptor (AR) expression in breast cancers may serve as a prognostic and predictive marker. We examined the expression pattern of AR and its phosphorylated forms, Ser-213 (AR-Ser(P)-213) and Ser-650 (AR-Ser(P)-650), in breast cancer and evaluated their association with clinicopathological parameters. Methods-Immunohistochemistry was performed on primary and distant metastatic breast cancers and benign breast tissue using antibodies against AR, AR-Ser(P)-213, and AR-Ser(P)-650. The levels of cytoplasmic and nuclear expression were scored semiquantitatively using a histoscore. Results-Nuclear staining of AR was observed in all benign breast tissue and 67% of cancer cases. Nuclear and cytoplasmic AR-Ser(P)-213 was increased in breast cancers 2-fold (p=0.0014) and 1.7-fold (p= 0.05), respectively, compared to benign controls, whereas nuclear and cytoplasmic AR-Ser(P)-650 expression was decreased in tumors by 1.9-fold and 1.7-fold (both p<0.0001), respectively. Increased expression of nuclear or cytoplasmic AR-Ser(P)-213 was observed in metastatic breast cancers (1.3-fold, p=0.05), ER-negative (2.6-fold, p=0.001) and invasive ductal carcinoma (6.8-fold, p=0.04). AR-Ser(P)-650 expression is downregulated in

ACG case reports journal, 2018

Malignancies of the gallbladder are uncommon in the developed world. Collision tumors are also ex... more Malignancies of the gallbladder are uncommon in the developed world. Collision tumors are also extremely rare neoplastic phenomena. Given their scarcity, there are no guidelines for treatment, and prognosis is based on the more aggressive tumor type. We present a patient with a collision tumor consisting of signet-ring cholangiocarcinoma and large-cell neuroendocrine gallbladder carcinoma of the biliary tract, and we review the literature pertaining to biliary tract collision tumors and their management.

Annals of Cardiothoracic Surgery, 2017

Esophageal cancer is a serious malignancy with high mortality. The two common distinctive patholo... more Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. The precursor lesions are also unique to each subtype. Squamous cell carcinoma is more common in East Asia, is linked to smoking and tobacco use, more commonly involves the middle esophagus, and the precursor lesion is squamous dysplasia. Adenocarcinoma is more common in the United States and certain European countries, associated with obesity and gastroesophageal reflux disease (GERD), more commonly involves the distal esophagus, and the precursor lesion is Barrett's esophagus. Endoscopic surveillance with biopsy evaluation is the standard of care in high-risk groups. Endoscopic ablative therapies for early cancers have lower morbidity than surgery. Despite increased awareness, identification of high-risk groups and endoscopic surveillance, a large proportion of patients present with advanced cancers. Surgery and chemoradiation, either in neo-adjuvant or adjuvant setting, is the usual treatment for patients with advanced but resectable esophageal cancers. The prognosis and further management largely depends upon the pathologic tumor-node-metastasis (TNM) staging provided by the American Joint Committee on Cancer (AJCC) and the International Union against Cancer. Currently, the 7th edition of TNM staging system is being applied for prognostication and this is more focused on pathologic evaluation. Eighth edition of AJCC/UICC TNM staging has been introduced and will be implemented for clinical use in 2018.

Journal of Global Infectious Diseases, 2021

Gallbladder specimens are ditzel in surgical pathology and opportunistic diseases like cryptospor... more Gallbladder specimens are ditzel in surgical pathology and opportunistic diseases like cryptosporidiosis where they are easy to miss. We describe three cases of gallbladders with mucosal papillary hyperplasia with acute and chronic inflammation, all of which revealed cryptosporidiosis on complete histological evaluation. The patients were found to be HIV positive on further chart review. In the absence of clinical history, which is often the case with gallbladder specimens, the finding of mucosal papillary hyperplasia can be a reactive response to an infectious cause and can serve as a helpful clue to look for organisms with patience at higher magnification.

Journal of Gastrointestinal and Liver Diseases, 2017

Barrett’s esophagus (BE) is a premalignant condition. The incidence of adenocarcinoma in BE has b... more Barrett’s esophagus (BE) is a premalignant condition. The incidence of adenocarcinoma in BE has been reported to be between 0.1-3%. Dysplasia in BE is patchy and extensive biopsy sampling is labor intensive, low yield and does not eliminate the sampling error completely. Volumetric laser endomicroscopy (VLE) is expected to enable endoscopists to do targeted biopsy of dysplastic/cancerous lesions (not visible on white light endoscopy) among patients with BE. We reviewed 7 studies with a total of 62 subjects who had undergone VLE. Of 34 patients with available data, VLE correlated with histology in 17 subjects (50%). It missed the underlying diagnosis in one subject (2.9%). VLE led to inadvertent biopsy in 16 patients (47.1%), and led or would have led to upstaging of disease in 11 subjects (32.4%). In the entire cohort, the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of VLE for diagnosis of dysplasia, buried Barrett’s or intramucosal carcin...

American Journal of Clinical Pathology, 2016

World Journal of Gastroenterology, 2011

AIM: To determine the expression and clinical significance of transcriptional intermediary factor... more AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβRⅡ. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1γ was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFβRⅡ was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1γ overexpression were significantly higher in stage Ⅲ than in stage Ⅰ and Ⅱ CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome.

Hepatocellular neoplasms mainly consist of hepatic adenoma, hepatocellular carcinoma (HCC) and pr... more Hepatocellular neoplasms mainly consist of hepatic adenoma, hepatocellular carcinoma (HCC) and precuror lesions. Benign tumors such as hepatic adenoma, while usually not deadly, may cause signfincant clinical challenges inlcuding maligant transformation. HCC due to vaious etiologies is one of the major leading causes of cancer death worldwide. Although knowledge about HCC is expanding exponentially in recent years, treatment and prevention of HCC is still a big challenge, and requires our thorough understanding of the molecular mechanisms of hepatocarcinogenesis. In this review article, we summarize the recent findings on molecular genetic pathology of hepatocellular neoplasms that have potential clinical implication in diagnosis, prognostication, and/or therapy. Hepatic Adenoma Hepatic adenoma predominantly occurs in younger women who are of child-bearing age, with or without prolonged use of oral contraception or abnormal carbohydrate metabolism (i.e. familial diabetes mellitus, glycogen storage disease, or galactosemia). It is usually a single nodule and sporadic, but can present as multiple tumors (adenomatosis) and have a familial inheritance pattern (familial liver adenomatosis).

Applied Immunohistochemistry & Molecular Morphology, 2009

Introduction: Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not... more Introduction: Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. Methods: Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. Results: Immunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH. Conclusions: Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.

Journal of Gastrointestinal Cancer, 2009

Applied Immunohistochemistry & Molecular Morphology, 2009

Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. W... more Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. Immunohistochemical analysis revealed high expression (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) higher in FHF in relation to AVH. Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.

American Journal of Clinical Pathology, 2018

Case Reports in Gastrointestinal Medicine, 2017

Disseminated toxoplasmosis is uncommon in both immunocompetent and immunocompromised hosts with g... more Disseminated toxoplasmosis is uncommon in both immunocompetent and immunocompromised hosts with gastrointestinal involvement being rarely described. We report a case of disseminated gastrointestinal toxoplasmosis in an immunocompromised man who presented with one month of diarrhea and abdominal pain. Imaging showed thickening of the ascending colon and cecum. Esophagogastroduodenoscopy and colonoscopy biopsies revealedToxoplasma gondii, confirmed by immunostain. Symptoms completely resolved following treatment with pyrimethamine, sulfadiazine, and leucovorin. This case highlights the importance of including toxoplasmosis in the differential diagnosis of any immunocompromised individual presenting with gastrointestinal symptoms.

American Journal of Clinical Pathology, 2012

Ectopic urate crystal deposition at sites other than joints, connective tissue, and kidney is ext... more Ectopic urate crystal deposition at sites other than joints, connective tissue, and kidney is extremely rare in a patient with gout. We report a case of intestinal perforation secondary to urate crystals in a pancreatic pseudocyst in a patient with concomitant gout and rheumatoid arthritis. A 52-year-old man with a medical history of coronary artery disease, pancreatitis, pancreatic pseudocyst, gout, and rheumatoid arthritis presented to the hospital with abdominal pain, nausea, vomiting, and fever. Radiology showed a 10.4 × 7.8-cm pseudocyst of the pancreas directly abutting adjacent distal transverse colon and inferior aspect of the stomach. Serum uric acid level was normal, and rheumatoid factor level was raised at this time. A resected specimen of the transverse colon and the necrotic content of the pseudocyst were received in our pathology department. Grossly, the transverse colon showed ulcerated necrotic area on the serosal surface with a tract communicating with the luminal surface. The perforation site was confirmed microscopically. Nonaqueous alcoholic eosin staining (NAES) was used on formalin-fixed tissue to preserve the water-soluble urate crystals. Positively birefringent, needle-shaped urate crystals were demonstrated in the necrotic tissue from the pseudocyst and on the serosal surface and site of perforation of the transverse colon. Urate crystals in pancreatic pseudocyst most likely lead to intestinal perforation. To our knowledge, urate crystal deposition as a possible cause of intestinal perforation in a pancreatic pseudocyst has not been reported in the literature.

International journal of clinical and experimental pathology, Jan 23, 2010

Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the m... more Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the morphology and type of tissue that they resemble, such as rhabdomyosarcoma, which resembles skeletal muscle. However, the cell of origin is unclear in numerous sarcomas. Molecular genetics analyses have not only assisted in understanding the molecular mechanism in sarcoma pathogenesis but also demonstrated new relationships within different types of sarcomas leading to a more proper classification of sarcomas. Molecular classification based on the genetic alteration divides sarcomas into two main categories: (i) sarcomas with specific genetic alterations; which can further be subclassified based on a) reciprocal translocations resulting in oncogenic fusion transcripts (e.g. EWSR1-FLI1 in Ewing sarcoma) and b) specific oncogenic mutations (e.g. KIT and PDGFRA mutations in gastrointestinal stromal tumors) and (ii) sarcomas displaying multiple, complex karyotypic abnormalities with no specif...

International journal of clinical and experimental pathology, Jan 10, 2010

Carney complex is a syndrome that may include cardiac and mucocutaneous myxomas, spotting skin pi... more Carney complex is a syndrome that may include cardiac and mucocutaneous myxomas, spotting skin pigmentation, and endocrine lesions. Many patients with Carney complex have been shown to have a stop codon mutation in the PRKAR1A gene in the 17q22-24 region. Here we present the case of a 57 year-old man with multiple skin lesions and cardiac myxomas. Histology of the skin lesions showed lentigenous melanocytic hyperplasia and cutaneous myxomas, confirming the diagnosis of Carney complex. Lesional and control normal tissue from the patient were identified and sequenced for the PRKAR1A gene. A germline missense mutation was identified at exon 1A. This is the first report of this mutation, and one of the few reported missense mutation associated with Carney complex. This finding strengthens the argument that there are alternative ways in which the protein kinase A 1-alpha subunit plays a role in tumorigenesis.

Hypertension, 2008

Reduced β-adrenoreceptor signaling is associated with increased sympathoadrenal activity in hyper... more Reduced β-adrenoreceptor signaling is associated with increased sympathoadrenal activity in hypertensive patients and animal models of hypertension. However, the mechanism that accounts for this characteristic decline in β-adrenergic signaling is unclear. In the present study, we investigated renal phosphodiesterase 4B, which metabolizes cAMP. Immunoblot analysis detected only the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive (SS) rats, and Dahl salt-resistant rats. The phosphorylated (activated) form of the protein was present at 2-fold greater levels in Dahl SS rats than in spontaneously hypertensive rats and Dahl salt-resistant rats, whereas the unphosphorylated form of the protein was reduced by approximately one half in SS animals. In accord with immunoblot data, rolipram-inhibitable cAMP hydrolyzing activity, a measure of PDE4 activity, was ≈3-fold greater in kidney cytosolic extracts from SS rats ...

Cases Journal, 2009

Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is most frequently represent... more Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is most frequently represented by the mucosa-associated lymphoid tissue type. We describe a case of a 67-year-old woman who presented with fatigue, mild dyspnea, and consolidation on chest radiograph. The diagnosis of non-Hodgkin's lymphoma was established by transbronchial biopsy, and chemotherapy was then started. The patient was treated with 6 cycles of chemotherapy. She had good response to therapy and no progression of the disease was observed during a 4-year follow-up period. The clinical, radiological and histopathological features are described. This entity has an indolent course, good response to therapy and favorable prognosis. However, despite being an incidental radiological finding in a third of cases, this disease remains highly underdiagnosed.

Cancer, 2013

Background-Androgen receptor (AR) expression in breast cancers may serve as a prognostic and pred... more Background-Androgen receptor (AR) expression in breast cancers may serve as a prognostic and predictive marker. We examined the expression pattern of AR and its phosphorylated forms, Ser-213 (AR-Ser(P)-213) and Ser-650 (AR-Ser(P)-650), in breast cancer and evaluated their association with clinicopathological parameters. Methods-Immunohistochemistry was performed on primary and distant metastatic breast cancers and benign breast tissue using antibodies against AR, AR-Ser(P)-213, and AR-Ser(P)-650. The levels of cytoplasmic and nuclear expression were scored semiquantitatively using a histoscore. Results-Nuclear staining of AR was observed in all benign breast tissue and 67% of cancer cases. Nuclear and cytoplasmic AR-Ser(P)-213 was increased in breast cancers 2-fold (p=0.0014) and 1.7-fold (p= 0.05), respectively, compared to benign controls, whereas nuclear and cytoplasmic AR-Ser(P)-650 expression was decreased in tumors by 1.9-fold and 1.7-fold (both p<0.0001), respectively. Increased expression of nuclear or cytoplasmic AR-Ser(P)-213 was observed in metastatic breast cancers (1.3-fold, p=0.05), ER-negative (2.6-fold, p=0.001) and invasive ductal carcinoma (6.8-fold, p=0.04). AR-Ser(P)-650 expression is downregulated in

ACG case reports journal, 2018

Malignancies of the gallbladder are uncommon in the developed world. Collision tumors are also ex... more Malignancies of the gallbladder are uncommon in the developed world. Collision tumors are also extremely rare neoplastic phenomena. Given their scarcity, there are no guidelines for treatment, and prognosis is based on the more aggressive tumor type. We present a patient with a collision tumor consisting of signet-ring cholangiocarcinoma and large-cell neuroendocrine gallbladder carcinoma of the biliary tract, and we review the literature pertaining to biliary tract collision tumors and their management.

Annals of Cardiothoracic Surgery, 2017

Esophageal cancer is a serious malignancy with high mortality. The two common distinctive patholo... more Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. The precursor lesions are also unique to each subtype. Squamous cell carcinoma is more common in East Asia, is linked to smoking and tobacco use, more commonly involves the middle esophagus, and the precursor lesion is squamous dysplasia. Adenocarcinoma is more common in the United States and certain European countries, associated with obesity and gastroesophageal reflux disease (GERD), more commonly involves the distal esophagus, and the precursor lesion is Barrett's esophagus. Endoscopic surveillance with biopsy evaluation is the standard of care in high-risk groups. Endoscopic ablative therapies for early cancers have lower morbidity than surgery. Despite increased awareness, identification of high-risk groups and endoscopic surveillance, a large proportion of patients present with advanced cancers. Surgery and chemoradiation, either in neo-adjuvant or adjuvant setting, is the usual treatment for patients with advanced but resectable esophageal cancers. The prognosis and further management largely depends upon the pathologic tumor-node-metastasis (TNM) staging provided by the American Joint Committee on Cancer (AJCC) and the International Union against Cancer. Currently, the 7th edition of TNM staging system is being applied for prognostication and this is more focused on pathologic evaluation. Eighth edition of AJCC/UICC TNM staging has been introduced and will be implemented for clinical use in 2018.

Journal of Global Infectious Diseases, 2021

Gallbladder specimens are ditzel in surgical pathology and opportunistic diseases like cryptospor... more Gallbladder specimens are ditzel in surgical pathology and opportunistic diseases like cryptosporidiosis where they are easy to miss. We describe three cases of gallbladders with mucosal papillary hyperplasia with acute and chronic inflammation, all of which revealed cryptosporidiosis on complete histological evaluation. The patients were found to be HIV positive on further chart review. In the absence of clinical history, which is often the case with gallbladder specimens, the finding of mucosal papillary hyperplasia can be a reactive response to an infectious cause and can serve as a helpful clue to look for organisms with patience at higher magnification.

Journal of Gastrointestinal and Liver Diseases, 2017

Barrett’s esophagus (BE) is a premalignant condition. The incidence of adenocarcinoma in BE has b... more Barrett’s esophagus (BE) is a premalignant condition. The incidence of adenocarcinoma in BE has been reported to be between 0.1-3%. Dysplasia in BE is patchy and extensive biopsy sampling is labor intensive, low yield and does not eliminate the sampling error completely. Volumetric laser endomicroscopy (VLE) is expected to enable endoscopists to do targeted biopsy of dysplastic/cancerous lesions (not visible on white light endoscopy) among patients with BE. We reviewed 7 studies with a total of 62 subjects who had undergone VLE. Of 34 patients with available data, VLE correlated with histology in 17 subjects (50%). It missed the underlying diagnosis in one subject (2.9%). VLE led to inadvertent biopsy in 16 patients (47.1%), and led or would have led to upstaging of disease in 11 subjects (32.4%). In the entire cohort, the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of VLE for diagnosis of dysplasia, buried Barrett’s or intramucosal carcin...

American Journal of Clinical Pathology, 2016

World Journal of Gastroenterology, 2011

AIM: To determine the expression and clinical significance of transcriptional intermediary factor... more AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβRⅡ. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1γ was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFβRⅡ was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1γ overexpression were significantly higher in stage Ⅲ than in stage Ⅰ and Ⅱ CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome.

Hepatocellular neoplasms mainly consist of hepatic adenoma, hepatocellular carcinoma (HCC) and pr... more Hepatocellular neoplasms mainly consist of hepatic adenoma, hepatocellular carcinoma (HCC) and precuror lesions. Benign tumors such as hepatic adenoma, while usually not deadly, may cause signfincant clinical challenges inlcuding maligant transformation. HCC due to vaious etiologies is one of the major leading causes of cancer death worldwide. Although knowledge about HCC is expanding exponentially in recent years, treatment and prevention of HCC is still a big challenge, and requires our thorough understanding of the molecular mechanisms of hepatocarcinogenesis. In this review article, we summarize the recent findings on molecular genetic pathology of hepatocellular neoplasms that have potential clinical implication in diagnosis, prognostication, and/or therapy. Hepatic Adenoma Hepatic adenoma predominantly occurs in younger women who are of child-bearing age, with or without prolonged use of oral contraception or abnormal carbohydrate metabolism (i.e. familial diabetes mellitus, glycogen storage disease, or galactosemia). It is usually a single nodule and sporadic, but can present as multiple tumors (adenomatosis) and have a familial inheritance pattern (familial liver adenomatosis).

Applied Immunohistochemistry & Molecular Morphology, 2009

Introduction: Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not... more Introduction: Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. Methods: Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. Results: Immunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH. Conclusions: Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.

Journal of Gastrointestinal Cancer, 2009

Applied Immunohistochemistry & Molecular Morphology, 2009

Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. W... more Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. Immunohistochemical analysis revealed high expression (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) higher in FHF in relation to AVH. Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.