Case Of Signet Ring Cell Carcinoma Research Articles

Comparative analysis of tumor biology and prognosis in mucinous and signet-ring cell colon cancers versus classical adenocarcinoma.

Background: Limited information is currently available on the natural history and prognosis of two distinct histological subtypes of adenocarcinoma (AC) in the colon: mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC). Therefore, the aim of this study is to examine the clinicopathological characteristics of colon MAC and SRCC, comparing them to classical AC, using a large cohort of cases from the United States. Methods: Patients diagnosed with colon AC, MAC, or SRCC from the SEER database between 2000 and 2018 were included in our study. Incidence trends, patient demographics, tumor characteristics, treatment, and survival were analyzed. Results: In our study, we analyzed a total of 310,813 patients with colon cancers, including 271,382 cases of classical AC, 34,750 cases of MAC, and 4,681 cases of SRCC. Over the study period, we observed a decline in the age-adjusted incidence rates of colon AC, MAC, and SRCC. Notably, the MAC and SRCC cohorts differed significantly from AC in terms of patient characteristics, tumor locations, and treatment patterns. Patients with MAC and SRCC had poorer survival outcomes compared to those with AC. Factors associated with worse survival included older age, male sex, poorly differentiated tumors, advanced stage, and the presence of MAC or SRCC histology. On the other hand, surgical intervention was associated with improved survival. Conclusion: Our study underscores the significance of recognizing the distinct features and outcomes associated with different histological subtypes of colon cancer. Further research is warranted to delve into the underlying biological traits that contribute to these differences and to develop more tailored treatment strategies.

Primary Signet Ring Cell Mucinous Adenocarcinoma of the Urinary Bladder: A Rare Case Report

Primary ‘signet ring mucinous adenocarcinoma’ is most commonly located in the stomach. The bladder is an uncommon presentation site for the primary location of this tumor. Mucinous signet-ring adenocarcinoma with urinary bladder as the primary origin is uncommon, accounting for fewer than two percent of all upper urinary tract carcinomas. The presence of signet ring cells, which is caused by compression and displaced nucleus of the cell into a crescent placed in the periphery along the cell wall, is a distinguishing feature of signet ring cell carcinoma. These cells are loaded with cytoplasmic mucus-containing vacuoles. Lower than one-third of primary bladder signet ring cell carcinoma cases show this gross morphology showing linitis plastica pattern with subepithelial infiltration without producing an exophytic mass in a pure signet ring cell carcinoma. Because this tumor shares histological features with the adenocarcinomas originating in several other sites, such as the prostate, digestive tract, and reproductive system, immunohistochemistry tests are required to confirm the bladder as the primary origin. Owing to the paucity of the neoplasm and the difficulty in locating the underlying tumor, site identification is frequently prolonged, leaving palliative care as the only choice for roughly half of the patients. This study depicts a rare case report of primary vesicular signet ring cell mucinous adenocarcinoma that considerably invades the pelvis and retroperitoneum's prostate and lymph nodes. This case emphasizes the significant characteristics of bladder mucinous adenocarcinoma, such as the sequence of tumor spread, the propensity for preliminary diagnostic errors, the microscopic pattern, and the significance of immunohistochemistry for defining its primary root from the bladder and selecting the most suitable intervention from the start.

Role of crush cytology in detecting gastrointestinal malignancies

Background: Adenocarcinomas are the most common malignancy of the gastrointestinal (GI) tract. Crush cytology is an effective method which can be used to detect neoplastic conditions of GI tract, especially in combination with biopsies. Materials and Methods: The objectives of the study were to study the efficacy of crush cytology as a convenient and near accurate method to evaluate endoscopic biopsy of GI neoplasms. Study Design: Retrospective and Prospective. The original cytopathology diagnoses were correlated with histology report on cases sent over 2-year period. In consecutive 89 patients attending the department of gastroenterology with clinical suspicion of malignancy, an endoscopy was performed. The material obtained was subjected to cytology as well as histopathology. The stained cytology slides along with corresponding histopathology slides were studied. Results: Out of 89 cases, both crush smear and histopathology sections were positive for malignant cells (65 cases), both negative for malignant cells (seven cases), crush smear positive and histopathology negative (three cases), and crush smear-negative and histopathology positive (14 cases). Out of the 14 cases which were negative in crush smears for malignancy, on histopathological examination, eight were signet-ring cell carcinoma, three were poorly differentiated adenocarcinoma, two turned out to be neuroendocrine carcinoma, and one non-Hodgkin lymphoma (NHL). Conclusion: Crush cytology smears can be used to diagnose malignant GI cases fairly accurately. Cases of signet-ring cell carcinoma, neuroendocrine tumor, poorly differentiated malignancy, and NHL may be missed by crush cytology technique alone. A special stain for mucin can be used to identify the signet-ring cells in signet-ring cell carcinoma cases.

Signet Ring Cell Carcinoma at the Ampulla of Vater: A Very Rare Diagnosis

Signet ring cell carcinoma (SRCC) is a rare lesion in the gastrointestinal tract. Further, the condition is very uncommonat the ampulla of Vater. A majority of the reported cases are typical, gland-forming adenocarcinomas. In our case, a patient aged 59 years, was diagnosed as a case of peri-ampullary carcinoma based on physical exam findings and imaging. Ultrasonography (USG) abdomen and magnetic resonance cholangiopancreatography (MRCP) revealed an enlarged common bile duct (CBD)and there was a presence of stricture at the terminal CBD. Endoscopic retrograde cholangiopancreatography (ERCP)showed growth at the ampulla of Vater. An endoscopic ultrasound guided needle core biopsywas obtained.Histopathological examination revealed the case as SRCC at the ampulla of Vater.We presentthis as an uncommon case of SRCC at the ampulla of Vater.

S2124 Shisto or No?: A Rare Case of Signet Ring Cell Carcinoma of the Rectum Mimicking Schistosomiasis

Introduction: Signet ring cell carcinoma (SRCC) of the rectum is a rare type of colorectal cancer with an incidence of less than 2%. SRCC is associated with poor prognosis, and often diagnosed at an advanced stage. While rare in the general population, SRCC occurs in up to 25% of schistosomiasis associated colorectal cancer. We report a case of SRCC in a patient with clinical features that mimicked colorectal and genitourinary schistosomiasis. Case Description/Methods: A 38-year-old male immigrant from rural Cuba presented with a 3 month history of urinary retention, intermittent fevers, and hematuria requiring placement of indwelling foley. Physical exam and vital signs were otherwise normal. Hb was 8.5 G/DL, MCV 85 fl, Creatinine 1.7 mg/dL. CT of the abdomen and pelvis with IV contrast revealed severe bilateral hydroureteronephrosis, concentric bladder wall thickening, splenomegaly, enlarged bilateral inguinal lymph nodes, and concentric submucosal thickening of the distal sigmoid/rectum with extensive calcifications. Colonoscopy revealed severe, diffuse, circumferential inflammation, narrowing, and ulceration from anus to sigmoid. While colitis was suspected, rectosigmoid biopsy showed mucinous adenocarcinoma with signet ring cell features. While we suspected schistosomiasis, Schistosoma IgG Ab was normal. The patient was advised to undergo further workup and chemotherapy, but he declined further treatment (Figure). Discussion: Schistosomiasis is a parasitic disease known to have an association with bladder neoplasia and gastrointestinal manifestations in the form of colitis and rectal calcifications. We suspect that due to his extensive rectosigmoid cancer our patient presented with features mimicking schistosomiasis, namely extrinsic genitourinary compression causing hydroureteronephrosis with hematuria, and cancer appearing like colitis. This case is instructive in that we are reminded of the interesting presentation of schistosomiasis as well as the occasional presence of signet cell cancer in the lower gastrointestinal tract. While the majority of SRCC arise in the stomach, occasionally this entity can present as an isolated primary SRCC of the rectum. Treatment with targeted therapy and chemotherapy have limited effect on improving survival. In conclusion, though SRCC of the rectum is rare, clinicians should consider this in the differential in patients presenting with risk factors for both schistosomiasis and SRCC of the rectum.Figure 1.: A, CT of the pelvis with IV contrast showing concentric submucosal thickening of the distal sigmoid/rectum with calcifications. B, Colonoscopy showing severe circumferential inflammation, narrowing, and ulceration of the sigmoid colon.

Clinicopathological characteristics of signet-ring cell carcinoma derived from gastric fovelar epithelium.

We aimed to investigate the immunophenotype, differential diagnosis, and clinicopathological characteristics of signet-ring cell carcinoma (SRCC) derived from gastric foveolar epithelium. Clinical characteristics, endoscopic findings, histopathological features, and follow-up data of seven cases of SRCC derived from gastric foveolar epithelium with small intramucosal lesions were analyzed. Seven patients with a mean age of 38.3 years were diagnosed with SRCC derived from gastric foveolar epithelium and small intramucosal lesions, all of them were negative for CDH-1 germline mutation. The glands proliferated and expanded, and then morphologically transformed into signet-ring cells and formed clonal hyperplastic SRCC, which expanded laterally along the gastric foveolar cells to a length of 3-6 mm. Periodic acid Schiff staining was positive, while CK7 and MUC6 were negative, in all cases. Ki-67-positive cells ranged 37%-60%. During a follow-up period of 6-30 months, no patients experienced tumor recurrence or metastasis. SRCC derived from gastric foveolar epithelium is originated from the proliferative region of the bottom of the gastric pit and gland neck. It is easily missed diagnosed or misdiagnosed as it grows laterally along the gastric foveolar cells. Biological behavior, genetics, and etiology of such SRCC, as well as the clinicopathological characteristics, need to be further studied.

Application of Imaging Indicators Based on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Colorectal Peritoneal Carcinomatosis.

ObjectiveThe imaging features of peritoneal carcinomatosis (PC) with different locations and pathological types of colorectal cancer (CRC) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were analyzed and discussed.MethodsThe PET/CT data of 132 patients with colorectal peritoneal carcinomatosis (CRPC) who met the inclusion and exclusion criteria between May 30, 2016, and December 31, 2019, were collected and analyzed. Observations included the location and pathological type of CRC, the peritoneal cancer index (PCI), standardized uptake maximum value (SUVmax), and retention index (RI) of the CRPC. Statistical analysis was performed using SPSS 20.0 software, and P < 0.05 was considered statistically significant.Results(1) The range of the PCI in the 132 patients studied was 2–30, with a mean value of 7.40 ± 8.14. The maximum long diameter of the CRPC lesions ranged from 0.6 to 12.1 cm, with an average of 3.23 ± 1.94 cm. The SUVmax ranged from 1.2 to 31.0, with a mean value of 9.65 ± 6.01. The SUVmax and size correlation coefficient for maximal CRPC lesions was r = 0.47 (P < 0.001). The RI range of the 72 patients who underwent time-lapse scanning was -10.0–112.2%, with RI quartiles of 13.5–48.9%; RI was ≥5% in 65 cases and <5% in seven cases. (2) The patients were grouped by the location of their CRC: the right-sided colon cancer (RCC, n = 37), left-sided colon cancer (LCC, n = 44), and rectal cancer groups (RC, n = 51). There were significant differences in the CRC pathological types (P = 0.009) and PCI scores (P = 0.02) between the RCC and RC groups and the RI between the RCC group and the other two groups (P < 0.001). (3) There were 88 patients organized into three groups by the pathology of their CRC: the moderately well-differentiated adenocarcinoma (group A, n = 57), poorly differentiated adenocarcinoma (group B, n = 16), and mucinous adenocarcinoma groups (group C, n = 15 cases, including one case of signet-ring cell carcinoma). There were significant differences in the CRC position (P = 0.003) and SUVmax (P = 0.03) between groups A and C.ConclusionThe PCI, SUVmax, and RI of peritoneal metastatic carcinoma caused by CRC in different locations and pathological types vary. Mucinous adenocarcinoma and poorly differentiated adenocarcinoma are relatively common in the right colon, and the PCI of peritoneal metastatic carcinoma is fairly high, but the SUVmax and RI are somewhat low.

Signet-ring cell carcinoma of the duodenal bulb presenting with gastrointestinal hemorrhage: a case report and literature review

BackgroundPrimary duodenal cancer (PDC) is rare, especially signet-ring cell carcinoma (SRCC) of the duodenal bulb, and it is commonly misdiagnosed as an ulceration. Here, we report a rare case of SRCC of the duodenal bulb presenting with gastrointestinal hemorrhage in an 82-year-old man.Case presentationAn 82-year-old man was admitted for gastrointestinal hemorrhage. Physical examination revealed upper abdominal tenderness and pale appearance, but was otherwise unrevealing. Laboratory workup was significant for anemia. Imaging showed no abnormalities. Two endoscopic evaluations along with interventional embolization were attempted and, unfortunately, adequate hemostasis was not achieved, resulting in distal subtotal gastrectomy, including the duodenal bulb. SRCC of the duodenal bulb was diagnosed based on pathology after surgery. Post-operatively, the patient experienced persistent gastrointestinal bleeding. Family declined further intervention and the patient eventually died one month post-resection.ConclusionsSRCC in the duodenal bulb is difficult to diagnose. For those with high-risk factors, endoscopic examination and biopsy are recommended. For patients who can receive radical tumor resection, pancreaticoduodenectomy (PD) is considered a first-line option. Early diagnosis and resection have been shown to improve prognosis.

The correlation of epithelial-mesenchymal transition-related gene expression and the clinicopathologic features of colorectal cancer patients in Taiwan.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the world. It has been the most prevalent malignancy in Taiwan for consecutive thirteen years. Despite the diversity of its etiologic and pathophysiologic factors, a biological process named as epithelial-mesenchymal transition (EMT) is indispensable in the progression of epithelial cancer. Our aim is to investigate the correlation between the expression of 8 EMT-related proteins (E-cadherin, β-catenin, claudin-1, CD44, N-cadherin, fibronectin, vimentin, S100A4) and the clinicopathologic features of CRC in Taiwan, along with the DNA CpG epigenetic status of CD44 gene. In immunohistochemical assessment, decreased expression of E-cadherin is statistically associated with the progression of cancer stage, while decreased expression of claudin-1 as well as increased β-catenin nuclear translocation and N-cadherin expression is statistically associated with the progression of histopathologic grade. E-cadherin, nuclear β-catenin and claudin-1 are also associated with other important prognostic factors, including nodal metastasis, tumor deposits, and elevated serum CA 19–9 levels. In addition, the left-sided colon and rectal cancers show increased nuclear translocation of β-catenin compared to the right-sided colon cancers, while the rectal cancers show increased fibronectin expression compared to the right-sided and left-sided colon cancers. Moreover, vimentin is aberrantly expressed in one case of signet-ring cell carcinoma. The DNA methylation levels of CD44 gene promoter between the tumoral and non-tumorous tissues by NGS comparison showed statistical difference on six CpG sites. However, such difference may not be sufficient because these DNA methylation proportions are too low to inactivate CD44 gene. Our results demonstrate the expression of E-cadherin, claudin-1, and nuclear β-catenin is closely related to the clinicopathologic prognostic determinants of CRC in Taiwan. The DNA methylation level of CD44 gene and its protein expression, however, show no correlation with the clinicopathologic features in CRC.

Diagnostic and treatment challenges of a case of primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid

BackgroundPrimary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is an extremely rare but aggressive neoplasm diagnosed primarily in elderly men. Until now there are 32 published cases of signet-ring cell carcinoma or histiocytoid carcinoma of the eyelid. We report the clinical, radiographic and histological features of the 33rd reported case of PCSRCC in the eyelid of a 73-year-old male, and review diagnostic and treatment challenges of this rare entity.Case presentationOur case highlights a 73-year-old male who was referred for surgical correction of right eye ptosis that was present for 2 years. Upon assessment, he was noted to have an upper lateral orbital rim mass. Computed tomography (CT) noted ill-defined soft tissue thickening anterior to the right globe, predominantly pre-septal but with slight post-septal extension. The pathology revealed diffusely and deeply infiltrating tumour cells extending through the dermis, subcutis, orbicularis muscle bundles and nerve fibers; the tumour cells were noted to have a monotonous histiocytoid appearance with foamy granular eosinophilic cytoplasm. At high magnification, intracytoplasmic vacuoles and occasional intermixed signet ring cells were identified. Immunohistochemical staining revealed the tumour cells to be AE1/AE3, CK7, GCDFP-15, E-cadherin, androgen receptor stain and GATA3 positive. Final pathology report confirmed the diagnosis of primary cutaneous signet-ring cell/histiocytoid carcinoma. Further imaging failed to identify a distant primary malignancy or metastatic disease. The decision was made to attempt surgical excision of the tumor. After the bulk of the grossly apparent tumor was removed, intraoperative frozen sections were sent. Superficial biopsies of the right periorbital region were performed, which revealed extension significantly further than the gross disease. Thereafter, the patient underwent a wide orbital exenteration with reconstruction using a temporary split-thickness skin graft. Due to positive margins on final permanent sections, the patient underwent further wide resection with free muscle-skin flap reconstruction followed by adjuvant radiation treatment.ConclusionOur case represents the 33rd case of primary signet-ring cell/histiocytoid carcinoma of the eyelid in a 73-year-old male, the first documented case with GATA3 positivity and the second documented case with androgen receptor stain positivity.

S1710 Signet Ring Cell Mucinous Adenocarcinoma of the Colon Manifesting as Intermittent Hiccups

INTRODUCTION: Signet-ring cell mucinous adenocarcinoma is an unusual phenomenon, accounting for less than one percent of all colorectal cancers. In this case report, we describe the instance of an adult male whose symptoms of intermittent hiccups and right lower quadrant pain were actually bellwethers of an exceedingly rare and aggressive underlying malignant process. CASE DESCRIPTION/METHODS: A 59 year-old male with past medical history of vitiligo, cholelithiasis, and left inguinal hernia repair, presented to the Emergency Department (ED) with intermittent hiccups and abdominal discomfort. He described that these symptoms had progressed to nausea, vomiting, and a thirty-pound weight loss over a two-month period. Prior ED visits at two separate hospitals had diagnosed the patient with constipation and discharged him home. Upon admission, the patient was hemodynamically stable and labs were significant for a leukocytosis of 16.6 K/uL, potassium of 2.1 mmol/L, BUN/creatinine of 74/2.78 mg/dL, total bilirubin of 1.5 mg/dL, and a lipase of 843 U/L. Computed tomography (CT) of the abdomen and pelvis revealed a new small ascites collection and peritoneal carcinomatosis, suggestive of adenocarcinoma (Figure 1). CA 19-9 and CEA were elevated to 1477 U/mL and 4.9 ng/mL, respectively. Colonoscopy was performed, which identified friable mucosa at the sigmoid colon that was sent for biopsy (Figure 2). Based on histologic analysis, the patient was diagnosed with signet-ring cell mucinous adenocarcinoma of the sigmoid colon (Figure 3). Further work-up found evidence of metastases to the gallbladder and peritoneum, and the patient ultimately died from complications of his disease less than two months from the initial date of diagnosis. DISCUSSION: Signet-ring cell carcinoma (SRCC), with a reported incidence of 0.1% to 0.9% in the colon, is known for its distinctive “linitis plastica” appearance and aggressive disease pattern. In healthcare, we tend to attribute benign symptoms to common and less harmful diagnoses, often to the detriment of the patient. As with the patient described here, cases of signet-ring cell carcinoma are typically diagnosed at a more advanced tumor stage and in younger individuals compared to other colorectal cancers. SRCC most frequently metastasizes to the peritoneum and confers a particularly poor prognosis once it has done so, despite systemic or intraperitoneal chemotherapy. This case illustrates the need for critical thinking and thorough evaluation of even the most benign presenting symptoms.Figure 1.: CT Abdomen/Pelvis demonstrating peritoneal carcinomatosis.Figure 2.: Colonoscopy revealing erythema and friable mucosa at the sigmoid colon.Figure 3.: Sigmoid biopsy reveals pools of mucin dissecting through the lamina propria and submucosa. Within the mucin pools are malignant appearing epithelial cells, some showing signet ring morphology.

Primary signet ring cell carcinoma of the breast: A rare entity with unique biological behavior—A clinical study based on pure signet ring cell carcinoma cohort

BackgroundPrimary signet ring cell carcinoma (SRCC) of the breast is a rare entity, and only a few case reports of the pure SRCC cases could be found in English literatures. We summarized the clinicopathological characteristics of a relatively large cohort of pure breast SRCCs for the first time. MethodsWe reviewed the medical records of 23 cases of pure breast SRCC with a median follow-up time of 70 months. ResultsThree patients had bilateral primary breast cancer (BC) and two of them had bilateral pure SRCCs. 30 % of patients had the malignant tumor family history including two bilateral BC patients. Malignant calcification was observed in 35.3 % of mammography images. Multifocal lesions were microscopically found in 26.1 % of cases. 63.6 % of the cases had lymph node metastasis, 45.5 % were classified as Stage III, 69.6 % had high value of Ki-67 index, and 34.8 % were triple negative subtype. 19.0 % of patients had local recurrence, and 52.6 % had distant metastasis. Four in five patients with positive tumor family history and follow-up data had relapse of SRCC. The 5-year overall survival rate was 73.7 %, the 5-year relapse-free survival rate was 54.3 %, and the 5-year breast cancer specific survival rate was 78.3 %. ConclusionPure SRCC of the breast showed an aggressive behavior. Neoadjuvant chemotherapy could be considered, breast-conserving surgery should be prudently chosen, and axillary lymph node dissection may be necessary. The high rate of positive tumor family histories and high bilateral incidence, which showed an adverse effect on prognosis, indicate the unique genetic burden of SRCC.

3230 Metastatic Signet Ring Cell Carcinoma to the Pelvis in a Young Female

INTRODUCTION: Gastric Cancer is the fifth most frequently diagnosed cancer in the world. While the incidence of gastric cancer has been decreasing, the incidence of signet-ring cell carcinoma (SRCC) continues to increase; with data from 2014 SEER analysis showing incidence of 0.4 per 100,000 cases [1-3]. The incidence of SRCC has increased ten-fold between 1970 and 2000 [3]. SRCC tends to occur in younger patients with a mean age ranging from 55 to 61 years [4]. Here we present a case of SRCC in a 23-year-old female with metastasis to the pelvis. CASE DESCRIPTION/METHODS: 23-year-old female w/medical history of iron deficiency anemia presents with 6 months of abdominal pain, nausea, vomiting and 20-pound weight loss. CT scan showed a 4 cm mass of the right pelvic side wall contiguous with the uterus and ascites. Recent endoscopy showed a 4 cm ulcerated mass in the body of the stomach, pathology was positive for poorly differentiated adenocarcinoma with signet ring cell features invading the lamina propria positive for CK20, CK7, AE1/3, EMA. Patient underwent laparoscopy, pelvic washing and peritoneal biopsy, which was positive for malignant cells. The immunostains were positive for CK7, Ber-EP4, MOC31; consistent with gastric adenocarcinoma. Further imaging did not show any distant metastasis and she was referred to oncology after discharge for further treatment. DISCUSSION: SRCC carries a poor prognosis and therapeutic strategy remains unclear; overall prognosis depends on the stage of the cancer [3]. Some studies have shown that prognosis of early stage SRCC cancer might be equivalent to other gastric adenocarcinomas. On the other hand, prognosis of advanced SRCC is very poor with a 5-year survival rate as low as 9% [3]. SRCC differs significantly from non-SRCC oncogenic pathway, as it involves loss of cell-cell adhesion and collection of mucin in large vacuoles. It has been shown that e-cadherin deficiency might initiate carcinogenesis in SRCC at an earlier stage than other cancers [3]. Furthermore, as compared to non-SRCC cancers, gastric SRC patients has reduced sensitivity to chemotherapy [5]. Young patients with SRCC tend to present with more advanced disease; however, they have improved survival as compared to older patients [6]. This is consistent with our young female patient, who presented with metastatic disease. Further studies need to be done concerning treatment strategies and prognostic factors in young patients who present with advanced SRCC.

Potential of Helicobacter pylori-uninfected signet ring cell carcinoma to invade the submucosal layer.

The typical histology of Helicobacter pylori-uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H.pylori-uninfected patient and its prevalence in diffuse-type gastric cancer (DGC) within Japan. We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H.pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA. Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H.pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P<0.01). Twenty-two (6.4%) patients, including two with submucosal invasion, were negative for H.pylori and had mucosal SRCC component in the cancer lesions. Of the 259 SRCC cases (pure SRCC or SRCC+PDA), H.pylori-uninfected cases had different clinicopathological characteristics compared with H.pylori-positive cases. Particularly, the ratio of patients with submucosal invasive SRCC was significantly lower in the H.pylori-uninfected gastric cancer group than in those with H.pylori infection. Helicobacter pylori-uninfected gastric cancer is not rare among pure DGC patients in Japan. SRCC in patients without H.pylori infection is less likely to be invasive.

A Case of Signet-ring Cell Carcinoma of the Breast Estimated by Fine Needle Aspiration Biopsy

A Case of Signet-ring Cell Carcinoma of the Breast Estimated by Fine Needle Aspiration Biopsy

The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas.

Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ(2) analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P<0.05). On multivariable analysis; radiation improved OS and DSS (adjusted hazard ratio [aHR], 0.592 and 0.589, respectively), pancreatectomy improved OS and DSS (aHR, 0.360 and 0.355, respectively), and combination therapy improved OS and DSS (aHR, 0.295 and 0.286, respectively). Age, site, and stage were also independent predictors of OS and DSS. Subgroup analysis demonstrated treatment to be an independent predictor of OS and DSS in localized/regional disease, in distant disease, and in patients diagnosed between 2000 and 2013. Age, site, stage, and treatment independently predict OS and DSS in pancreatic SRCC.

Crohnʼs Disease Masquerading Ileal Signet Ring Cell Carcinoma: Case Report

Introduction: Signet ring cell carcinoma (SRCC) is a rare highly malignant adenocarcinoma that mainly originates in the stomach. Small bowel malignancies are rare, accounting for only 3% of all gastrointestinal tract neoplasms. We report a case of SRCC of the terminal ileum (TI) that was masqueraded by the presence of Crohn's disease (CD). Case Presentation: A 67-year-old man with a 49 year history of ileal CD, symptomatically controlled with Mesalamine, had recent changes in bowel habits. Endoscopy revealed normal-appearing colon and proximal ileal stricture at 10-15 cm from the Ileocecal valve. Six months later, computed tomography enterography demonstrated 2 long segments of ileal wall thickening and enhancement, suspicious of active disease. Over the next 4 months, he continued to have intermittent attacks of abdominal cramping, bloating, and borborygmus. He was treated with oral prednisone for suspected partial inflammatory small-bowel obstruction. Due to lack of improvement and weight loss, he underwent laparoscopic ileocecectomy with ileocolic anastomosis. Histopathological demonstrated 2.5 cm mucin-producing, moderate/poorly differentiated ileal adenocarcinoma with signet ring cell features as well as 6 cm tubulovillous adenoma in the setting of active stricturing CD. Unfortunately, the tumor was metastatic, and chemotherapy was initiated. Discussion: Adenocarcinomas represent 25-40% of small bowel neoplasms and may be associated with longstanding inflammation. It is extremely rare for SRCC to originate from the TI. It is likely that in our patient, SRCC arose, in part, because of longstanding inflammation due to CD. Routine screening for small bowel malignancies should be considered in patients with CD even with symptomatic remission. Aggressive medical therapy (i.e. biologics) to control subclinical inflammation may be warranted.

Colorectal signet ring cell carcinoma: Influence of EGFR, E-cadherin and MMP-13 expression on clinicopathological features and prognosis.

Signet ring cell carcinoma (SRCC) is unique rare subtype of mucin-producing colorectal adenocarcinoma characterized by presence of signet ring cells, in >50% of the tumor tissue. This study aims to investigate expression of EGFR, E-cadherin and MMP-13 expression on clinicopathological features of signet ring cell type and its prognostic effect using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal cancer cases among which 19 cases of SRCC. High density manual tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for EGFR, E-cadherin and MMP-13 expression was done. We found that SRCC was significantly associated with younger age and more frequency of LN metastasis than all other groups. SRCC was also significantly associated with annular gross picture, more depth of invasion, advanced stage, more lymphovascular emboli, more perineural invasion and less arousal from an overlying adenoma. In conclusion, colorectal SRCC has distinctive clinicopathological and histological features with different unique mechanisms of carcinogenesis and more aggressive biologic behavior than other colorectal carcinoma subtypes. Negative/low expressions of EGFR and E-cadherin and MMP-13 were found in SRCC with no effect on the prognosis.

An Unusual Presentation of Gastric Signet Ring Cell Carcinoma: Lower Back Pain as the Primary Symptom

An Unusual Presentation of Gastric Signet Ring Cell Carcinoma: Lower Back Pain as the Primary Symptom A 50 year old Hispanic woman was admitted with a 6 hour history of severe, shooting mid/lower back pain radiating to the upper left abdomen, sudden in onset, 10/10 intensity. She denied nausea, vomiting, and diarrhea. She had an episode of burning epigastric pain 2 months ago that resolved spontaneously, as well as another episode of back pain. She also reported a recent 15 pound weight loss. She had an H. pylori infection in the past which was treated. Her sister died of breast cancer. She drank alcohol occasionally but denied any drugs or cigarette use. On physical exam, she had normal vital signs but had tenderness in the left upper abdomen and lower paraspinal region. Laboratory studies were unremarkable except for an elevated ALP and CEA. CT scan of the abdomen and pelvis with contrast revealed thickening of the stomach wall and multiple enlarged lymph nodes. CT of the chest without contrast was remarkable for lytic lesions in the sternum and in the T1-L1 spine. An esophagogastroduodenoscopy was done, showing a circumferential, fungating and firm ulcerated mass with friable surfaces in the gastric body. Endoscopic ultrasound showed circumferential mucosal and submucosal thickening with hypoechoic islands in the gastric body, eroding into the propria and serosa with several enlarged lymph nodes. Primary gastric signet ring cell carcinoma (SRCC) was diagnosed on biopsy and was staged as T3N3M1. She declined to have a bone biopsy to confirm metastatic disease. She was not a surgical candidate and was eventually discharged on a course of chemotherapy. This is a unique case of SRCC due to the presenting symptom of back pain. Gastric carcinomas, especially SRCC, typically do not metastasize to the bone. The common sites of metastasis are the lymph nodes (35.4%), peritoneum (30.3%), liver (24.3%), and lung (10.4%). This case highlights the importance of a thorough clinical workup, using a combination of history, physical, labs and imaging. Without this, an uncommon presentation of a serious disease would likely have been missed.FigureFigureFigure

Prognosis of Signet Ring Cell Carcinoma of the Colon and Rectum and their Distinction of Mucinous Adenocarcinoma with Signet Ring Cells. A Comparative Study

Signet ring cell carcinoma (SRCC) of the colorectum is very rare, comprising between <1% and 2.4% cases of colorectal cancer. Patients' prognoses are poor. Several case reports had described as SRCC cases that are mucinous adenocarcinomas (MAC) with signet ring cells (SRC). In order to clearly delineate between MAC with SRC and SRCC, we performed a retrospective study at a national cancer referral center in which survival and clinicopathological characteristics between these two forms were comparedand also SRCC were characterized by immunohistochemistry. We retrieved 32 cases that had been classified as either SRCC or MAC with SRC subtypes. It was noted that SRCC patients presented at older ages, demonstrated more advanced clinical stages, lymphovascular invasion, lymph node metastases, and higher carcinoembrionic levels than MAC with SRC patients. Regarding SRCC immunophenotype, 50% showed loss of CDX2 expression, 33% were CK20 negative, 41.7% were CK7 positive, and 25% were negative for both CK7 and CK20. For the MAC with SRC and SRCC groups, the median disease-specific survival (DSS) was 46.1months (95% CI 36.9-55.25) and 22.4months (95% CI 5.1-39.7 [p=0.039]), respectively. The 3-year DSS was 80.7% and 28.6% (p=0.017) for the MAC and SRCC patients, respectively. Univariate and multivariate analyses showed that SRCC was associated with decreased survival. SRCC had several clinicopathological features that permitted differentiation of MAC with SRC from SRCC patients, who had a poor DSS. A differential diagnosis for metastatic gastric cancer is only possible with a good clinicopathological correlation.