|Year : 2016 | Volume
| Issue : 2 | Page : 296-299
Profile of pancreatic tumors at a tertiary care center
P Nandan1, M Nirupama1, JR Kini1, S Gopal2, KK Sahu1, S Rai1
1 Department of Pathology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
2 Department of Gastroenterology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
|Date of Web Publication||6-Jan-2017|
Department of Pathology, Kasturba Medical College, Manipal University, Mangalore, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Pancreas, a relatively inaccessible organ, poses diagnostic difficulties with overlapping presentation among benign and malignant tumors. In the present study, pancreatic aspirates obtained by computed tomography (CT) guided procedures were used for cytodiagnosis. Our study aims at correlating clinical, cytological, biochemical, and histopathological results in obtaining a final diagnosis. Methodology: A retrospective study of 2 years was done which included 32 cases of pancreatic tumors at a tertiary care center. Patient data were retrieved and analyzed. Results: Twenty-seven of the 32 (84.37%) cases were malignant tumors. Age distribution in malignant tumors was predominantly seen in the fourth to eighth decade, whereas in benign, it ranged in the second to third decade. Thirteen out of the 32 (40.62%) cases reported were females, with male:female ratio of 1.46:1. The most common presenting symptom was abdominal pain followed by jaundice and vomiting. Three of the 32 cases had visceral metastasis at the time of diagnosis. CT-guided aspirates in most cases yielded diagnostic material. Cytological and histopathological results concurred except for three cases. Cancer Antigen 19-9 was worked up for 14 of 27 malignant cases, 11 of which showed grossly elevated values (700–7000), and three cases showed mildly elevated values (100–300). Three of the four benign cases worked up for CA 19-9 showed normal values. Conclusions: Among the mass forming lesions in pancreas, malignancy was more common compared to benign tumors. A multidisciplinary approach in the assessment and diagnosis of pancreatic tumors yields accurate results in spite of the limitations faced in obtaining adequate samples by needle aspirates.
Keywords: CA 19-9 antigen, pancreas, pancreatic ductal carcinoma, pancreatic neoplasms
|How to cite this article:|
Nandan P, Nirupama M, Kini J R, Gopal S, Sahu K K, Rai S. Profile of pancreatic tumors at a tertiary care center. Indian J Cancer 2016;53:296-9
| » Introduction|| |
The classification and diagnosis of pancreatic tumor is struck with a major difficulty, which incorporates etiology, pathogenesis, clinical features, and pathological findings. It is a difficult organ to access and its imagery is limited to ultrasound and cross-sectional imaging. Tumors arising from the pancreas present a peculiar challenge of early detection at preinvasive stages. The clinical presentation with symptoms is often in advanced stages.
Core needle biopsy and fine needle aspiration (FNA) are more likely to provide satisfactory results than wedge biopsy of abnormal pancreatic tissue. Pancreatic biopsy is considered to be the gold standard against other diagnostic approaches.
Aims and objectives
- To determine the age and sex distribution and percentage of malignancy in the study
- To correlate clinical, morphological, cytological, and biochemical results in obtaining a diagnosis
- To compare the diagnostic value of cytology of pancreas with the histomorphological results, wherever applicable.
| » Methodology|| |
Approval from the Institutional Ethics Committee was obtained.
A retrospective study period of 2 years was conducted in a tertiary care center. Study included collection of data from the patients' record sheets available in the Medical Records Department. Information pertaining to the cases was recorded and tabulated.
All investigated cases of primary pancreatic tumors of 2 years which were confirmed by histopathology were included in the study. Metastatic tumors and tumor-like lesions were excluded. Tumors were classified according to the WHO classification of tumors of endocrine and exocrine pancreas.
Data were entered and analyzed using SPSS version 23.0 (Armonk, NY: IBM Corp.). It is represented as proportions and percentages.
We encountered twenty cases of ductal adenocarcinoma (DAC), four cases of solid pseudopapillary neoplasm (SPN), three cases of neuroendocrine carcinoma, one case each of intraductal papillary mucinous neoplasm (IPMN), acinar cell carcinoma (ACC), spindle cell lesion, gastrointestinal stromal tumor (GIST), and mixed acinar-endocrine carcinoma (MAEC).
In the present study, a total number of twenty pancreatic DAC cases were studied. Out of the 20 cases, 11 cases were biopsies and the remaining were Whipple resection specimens.
Presentation was more common among males (70.0%). Age range varied from 28 to 73 with mean being 54.95 and median of 55.5 years. The most common presenting symptom was pain in the abdomen followed by jaundice in 4 cases and vomiting in 2 cases.
Cytological findings – most of the cases showed high cellularity smears with cells arranged in clusters having high nuclear:cytoplamic (N:C) ratio and prominent nucleoli in blood and necrotic background.
Histopathology showed features of well-differentiated DAC infiltrating into surrounding tissue with desmoplastic stroma.
Solid pseudopapillary neoplasm
The present study included a total of four cases of SPN. Two of the cases presented with pain in the abdomen while two others with incidental findings. All the four cases reported were females aged 13–29 years with a mean of 23 years.
Necrotic area was noted in one of the cases during computed tomography (CT) diagnosis.
Cytology of the tumor aspirates showed smears of high cellularity in branching papillary clusters and sheets, acini and singly scattered cells were monomorphic with round-to-oval nuclei. Nuclei showed fine granular chromatin and small nucleoli.
Distal pancreatectomy was planned for two of the cases and core needle biopsy specimen was received in two other cases for histopathological diagnosis. Microscopy of the tumor tissue was composed of pseudopapillae with hyalinized fibrovascular cores lined by serosal layers of bland epithelial cells with clear to eosinophilic granular cytoplasm, round-to-oval nuclei, finely stippled chromatin, indistinct nucleoli, occasional nuclear grooves, and few mitotic figures. Clusters of foamy cells were also seen. Few of the cells showed hyaline intracytoplasmic globules.
Intraductal papillary mucinous neoplasm
A 65-year-old man presented with abdominal mass and abdominal pain. CT revealed a huge solid cystic mass lesion in the body and tail of the pancreas and with multiple necrotic retroperitoneal lymph nodes. Lab results showed CA 19–9 129.3, carcinoembryonic antigen (CEA) 52.51, Random blood glucose (RBG) 245, urea 48, alanine aminotransferase, bilirubin normal, hemoglobin (Hb) 8.9, packed cell volume 28.0, white blood cell (WBC) 13,100, and erythrocyte sedimentation rate 76 with mild neutrophilia. Hbs and HIV were negative.
Cytology of the guided aspirates showed papillary clusters of cells with oval vesicular nuclei in a proteinaceous background, suggestive of cystic papillary neoplasm.
Microscopy of the core biopsy tissue was composed of fibrous stroma having a few scattered glands and a lining columnar epithelium, which is thrown into small papillary folds and composed of mucinous cells having nuclear hyperchromasia, mild atypia and stratification, and occasional mitosis with moderate amounts of granular eosinophilic cytoplasm.
Diagnosis of cystic IPMN of borderline malignant potential was made.
Acinar cell carcinoma
A 60-year-old man presented with painless obstructive jaundice, had a 5 cm mass in the head of pancreas resected by Whipple's operation; histopathological examination showed a typical ACC.
Spindle cell lesion
A 48-year-old male diabetic presented with abdominal pain for 2 weeks. Lab reports showed CEA 3.61, postprandial blood glucose 186, and fasting blood glucose 126 with normal serum amylase. Hbs and HIV were negative. Hb was 10.8 and WBC was 17,800, with neutrophilia, lymphocytopenia, and hypoalbuminemia.
CT revealed chronic calcific pancreatitis with mass-like lesion in tail. CT-guided FNA was performed and cytology showed features of chronic calcific pancreatitis. Gastrojejunostomy was carried out, and intraoperatively, a mass-like lesion adhered to the posterior wall of stomach, and duodenojejunal flexure was noted.
Sections from the core biopsy shows tumor tissue composed of spindle cells with scant cytoplasm. Nuclei were oval-to-spindle, elongated, and hyperchromatic. Background showed myxoid areas with sprinkling of spindle cells. Lymphocytes and eosinophils with prominent blood vessels were noted. No areas of necrosis was seen. Diagnosis of spindle cell lesion was made.
Gastrointestinal stromal tumor
A 66-year-old man presented with abdominal pain for 3 weeks. On CT, a well-defined multilobulated mildly enhancing mass abutting the distal second and proximal third part of the duodenum was noted. CT-guided FNA cytology was performed, but sample was inconclusive for definite opinion.
Biopsy sections from the linear tissue bits showed malignant tumor cells disposed in fascicles. These tumor cells were spindle-to-plump and round-to-oval with severe nuclear atypia, high N:C ratio, hyperchromatic nuclei, and scant eosinophilic cytoplasm. Majority of the tumor cells displayed paranuclear vacuoles. Few of the tissue bits showed tumor tissue completely replaced by necrosis. Following differentials were considered – leiomyosarcoma and malignant GIST. Immunotyping was done which revealed CD117-positive and smooth muscle actin focal positive for confirming the diagnosis of malignant GIST.
Mixed acinar–endocrine carcinoma
A 45-year-old woman presented with abdominal pain for 8 months and epigastric tenderness was noted on examination.
Contrast-enhanced CT (CECT) abdomen with angiogram revealed hypervascular mass in the head of pancreas. Whipple's resection was carried out and microscopy of the tumor showed neoplastic cells arranged in solid, lobules, trabecular, and gland-like patterns with scant intervening stroma and traversed by thin-walled blood vessels. At places, fibrohyalinized septae were seen intervening the lobules and solid sheets of tumor. Focally, the stroma was loose and edematous. The neoplastic cells had moderate eosinophilic cytoplasm, round-to-oval nuclei, granular chromatin with some of the cells showing high N:C ratio, enlarged hyperchromatic nuclei, and coarse chromatin-scattered bizarre nuclei.
A 66-year-old female patient presented with abdominal pain and altered bowel habits. The following were noted: CA 19–9 4922, CEA 8.66, Hb 10.5, WBC 21,000, and platelet count of 88,000. DLC revealed neutrophil 39 and lymphocyte 61. Upper gastrointestinal endoscopy reported malignant infiltration at D1–D2 junction. Cytology reported smear-positive for malignancy. Sections from the biopsy specimen showed cells with minimal-to-moderate cytoplasm, fine-stippled chromatin arranged in nests and cords in a desmoplastic stroma. Surrounding mucosa showed lymphoplasmocytic infiltrate admixed with eosinophils. Immunohistochemistry (IHC) revealed positive neuron-specific enolase (NSE) and MIB in 3% of the tumor cells, which was confirmatory for the diagnosis of neuroendocrine carcinoma.
A 50-year-old man presented with abdominal pain. Cytology of CT-guided fine needle aspirates was inconclusive. Whipple's resection was planned, and intraoperatively, mass arising from duodenojejunal flexure was noted. Mesentery was studded with lymph nodes, mass, and small bowel was excised. Sections of tumor tissue showed infiltrating fibroadipose tissue and extensive areas of hemorrhage, infarction, and edema. Immunophenotyping was done and MIB index of 12% was obtained to confirm the diagnosis of intermediate grade neuroendocrine tumor (NET).
A 47-year-old female presented with abdominal pain for 4 months in the epigastric region. CECT revealed a mass arising from the posterior wall of stomach/head of pancreas. Whipple resection was planned; intraoperatively, tumor was found to be arising from the head of pancreas, and was inoperable. Biopsy sections showed tumor tissue composed of medium-to-large-sized polygonal cells arranged in cohesive, sheets, nests, and trabecular pattern. The tumor cells exhibit round-to-oval nucleus, mild anisonucleosis, fine-to-coarse chromatin, and moderate-to-abundant amount of amphophilic cytoplasm. Scattered tumor cells showed prominent nucleoli and 8–10 mitosis/10 high-power fields were noted. Differential diagnosis of NET and ACC was considered. Immunophenotyping revealed synaptophysin strongly positive, chromogranin positive, and cytokeratin strongly positive to confirm the diagnosis of neuroendocrine carcinoma.
| » Results and Analysis|| |
A total of 32 pancreatic tumors were received over a period of 2 years in a tertiary care center. All the cases had both cytology and histopathology reports. Four cases were inadequate for conclusive cytological opinion, where histopathology was confirmative [Table 1] and [Graph 1].
|Table 1: Nature of sample received with cytohistopathological correlations|
Click here to view
The most common clinical presentation was abdominal pain followed by jaundice and vomiting. Two cases of SPN were incidentally detected and two cases were presented with abdominal pain.
CA 19-9 was worked up for 14 of 27 malignant cases, all of which had elevated values. Eleven cases had grossly elevated values (700–7000) and in the rest, it was mildly elevated (100–300). Three of the four cases of SPN were worked up for CA 19-9, all of which had normal values. A case of borderline malignancy (IPMN) showed mildly elevated CA 19–9 value (129.3).
Diagnostic value of cytology: The cytological reports had good sensitivity and specificity in cases of DAC, SPN, and IMPN whereas diagnosis of ACC, GIST, and MAEC was missed out in cytology [Table 2].
| » Discussion|| |
Solid pseudopapillary neoplasm
SPN can be witnessed in patients of all ages, but generally affect young females at a mean of 27.2 years with a female:male ratio of 8.37:1.
The clinical presentation of SPN is vague. It is incidentally detected during complementary imaging investigations such as ultrasound or CT scan of the abdomen. Some patients have indistinct presenting complaints including abdominal pain or discomfort, poor appetite, and nausea, which are attributed to tumor compression on neighboring organs. This is consistent with our findings.
DAC is the most common neoplasm of the pancreas accounting for approximately 85% of all pancreatic neoplasms. The patients are usually between 60 and 80 years of age and rarely less than 40-year-old. Men are affected slightly more common than women.,
Tumor marker CA 19-9 has shown to be 65–75% sensitive and 70–80% specific for pancreatic DAC., Our finding of 100% sensitivity to DAC could be due to the reported cases in advanced stages of the malignancy. Lower specificity of 60% could be due to the presence of tumor variants.
Gastrointestinal stromal tumor
Primary GIST in the pancreas is extremely rare, with only 21 reported cases in the English literature from 2000 to 2013.
The age of patients of the reported cases  varied from 31 to 84 with a mean of 55.0. Ten of the 21 cases were reported in males. Head of the pancreas was involved in 11 (48%) of the cases and in 5 (34%) cases in the tail. Findings of the present study are concordant with these data.
Spindle cell lesion
We encountered a rare spindle cell lesion of the pancreas composed of bland spindle cells with oval nuclei. No frank mitosis/necrosis were seen. Differentials of GIST and myofibroblastic tumors were considered. IHC showed CD117 negativity. Conclusion was limited by financial constraints.
NET frequently grows slowly, but displays a high degree of malignancy. Furthermore, the deficiency of a specific clinical presentation makes preoperative diagnosis the more challenging.
By definition, pancreatic NETs express neuroendocrine markers, synaptophysin and NSE, the proteins associated with the secretory apparatus of endocrine cells. Three cases of NETs reported in our study invariably showed synaptophysin and NSE positivity.
Mixed acinar–endocrine carcinoma
Even though pancreatic endocrine neoplasms and ACC are diverse entities, their pathological and morphological forms are at times very alike, and their components can be pooled. When each component exceeds 25% of the tumor, the state is defined as MAEC.
In our case, microscopy of the tumor tissue showed both acinar and endocrine differentiation and the neoplastic cells diffusely expressed the acinar and endocrine markers (trypsin, chymotrypsin, chromogranin A, and synaptophysin), which indicated that tumor differentiation was toward both acinar and endocrine carcinomas.
Based on these reported cases, 21 of 35 patients with MAEC of the pancreas were male and the male:female ratio was 1.5:1, signifying that MAEC affects both sexes. However, male patients may be more commonly affected, the scenario of which is similar to ACC. MAEC more commonly affects elderly with a mean age of 61.32 in the 35 reviewed cases. Detected at an earlier age in our present study, it was probably due to advanced diagnostic techniques and awareness.
A total of 32 pancreatic tumors were studied, along with the clinical data. DAC was most common in malignant tumors and SPN among benign. Most common presenting complaint of all tumors was abdominal pain.
| » Conclusions|| |
The correlation of clinical, serological, radiological, cytological, and histopathological findings is helpful in the early detection, diagnosis, and management of pancreatic lesions. Elevated CA 19-9 levels were a reliable indicator for DAC. However, histological examination with IHC remains gold standard for diagnosis and confirmation of all pancreatic tumors.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]