Metastatic Signet Ring Cell Carcinoma Research Articles

Metastatic signet-ring cell carcinoma of the urinary bladder: A novel management approach to a rare tumour.

Primary signet-ring cell carcinoma (SRCC) of the urinary bladder, a variant of adenocarcinoma, is exceedingly rare and as a result no gold standard exists for its management. We report a case of primary SRCC of the bladder with recurrent metastases; we utilized an innovative diagnostic approach and the patient exhibited a treatment response to palliative FOLFOX-6 chemotherapy.

Genital lymphoedema as an early symptom of a signet-ring cell carcinoma

ZusammenfassungEin 51-jähriger Mann stellt sich wegen eines rasch progredienten Bein- und Genitallymphödems vor. Die komplexe physikalische Entstauung bleibt ohne Erfolg. Nach ergebnisloser Bildgebung wird in der endoskopischen Exploration ein metastasierendes Siegelring-Karzinom der Kardia als Ursache nachgewiesen.

Metastatic signet-ring cell carcinoma of unknown primary origin

About 3–5% of metastatic cancers originate from an unknown primary origin. Some have a signet-ring cell (SRC) component. We report the medical history of three patients with SRC carcinoma expressing both the oestrogen (ER) and progesterone receptors (PR). Although no primary breast cancer could be identified, we considered these three patients as having metastatic breast cancer. All of them were therefore treated with standard breast anti-hormonal therapies and all demonstrated benefit. The pitfalls of clinical presentation, diagnostic work-up, and treatment are discussed.

Cytologic features of pancreatic adenocarcinoma with “vacuolated cell pattern.” report of a case diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

The "vacuolated cell pattern" has only been recently described as a distinct morphologic variant of pancreatobiliary adenocarcinoma. Herein, we report the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytologic features of a case of pancreatic adenocarcinoma with "vacuolated cell pattern" occurring in a 60-year-old man. The aspirate smears and cell block sections from the EUS-FNA of a 23.5 mm hypoechoic pancreatic head mass were highly cellular, showing variably-sized crowded three-dimensional cell clusters, flat sheets, and numerous highly atypical single cells. The background was bloody and showed necrotic debris, but no discernible mucus. The most striking feature of the aspirate was the presence of numerous very large (20-50 µm) vacuoles, occupying the entire cytoplasm, pushing the nuclei to the side and indenting them, that imparted a cribriform appearance to the sheets of neoplastic cells. The non-vacuolated neoplastic cells were large, had abundant dense (squamoid) cytoplasm, irregularly contoured hyperchromatic nuclei, and prominent macronucleoli. Histologic evaluation of the pancreatectomy specimen showed a "vacuolated cell pattern" adenocarcinoma composed of poorly formed glands, solid sheets, and infiltrating single cells with pleomorphic nuclei and large cytoplasmic vacuoles. To our knowledge, this is the first report describing the cytologic features of this rather uncommon morphologic variant of pancreatic adenocarcinoma. Recognition of this morphologic variant of pancreatic adenocarcinoma in ESU-FNA samples allows its differentiation from primary and metastatic signet-ring cell carcinomas.

A Case of Metastatic Signet Ring Cell Carcinoma Presenting as Tuberculous Peritonitis in an HIV/HCV Coinfected Patient

Purpose: New onset ascites is most commonly due to chronic liver disease, but infectious and malignant causes must also be considered. This is a case of new onset ascites due to metastatic gastric signet cell adenocarcinoma in a patient with chronic hepatitis C and HIV coinfection. Case: A 59-year-old male with HIV (CD4 54) and chronic hepatitis C presented with abdominal pain, nausea, weight loss, and increasing abdominal girth for 2 months. Physical exam revealed bulging flanks with fluid wave and dullness to percussion. Laboratory findings were significant for hypoalbuminemia, absence of transaminitis, or thrombocytopenia, and elevated INR. PPD and Quantiferon-TB tests were negative. Right upper quadrant ultrasound with vascular dopplers did not show cirrhotic features or vascular thrombus. Abdominal CT was negative for intraabdominal organ abnormality. Diagnostic and therapeutic paracentesis revealed a low serum albumin-ascites albumin gradient (SAAG) and high WBC count with monocytic predominance. Peritoneal fluid was tested for cytology, acid-fast bacilli smear, culture, and gram stain, which were all negative. Repeat diagnostic and therapeutic paracentesis again revealed a low SAAG, and adenosine deaminase (ADA) testing was elevated at 26.3 IU/mL. The patient underwent a diagnostic laparoscopy with peritoneal biopsy. On laparoscopy, innumerable peritoneal lesions were noted, grossly resembling tuberculous seeding of the peritoneum. The presumed diagnosis of tuberculosis peritonitis was made and anti-tuberculin therapy was initiated. The following day, pathology from the peritoneal biopsy specimen returned as metastatic signet cell adenocarcinoma. An esophagoduodenoscopy was performed revealing a large, firm ulcerated tumor in the greater curvature of the gastric body. Pathology was consistent with diffuse signet ring cell carcinoma. Conclusion: As demonstrated by a recent meta-analysis, the ADA test has a high sensitivity and high specificity for revealing tuberculous peritonitis in ascitic fluid. This case underscores the importance of the ADA pre-test probability and of confirming the diagnosis with peritoneal biopsy, as malignancy may also present with high ADA levels.Figure: Ulcerated gastric mass, greater curvature.

Metastatic Signet Ring Cell Carcinoma Presenting as a Thyroid Diffuse Involvement: Report of a Case Studied with Q-elastographic and Acoustic Radiation Force Impulse Imaging Features

Metastatic carcinomas to the thyroid are rare in daily clinical practice. However, when encountered they represent a diagnostic challenge, since it is difficult to distinguish them from primary thyroid lesions, especially when occurring in patients with occult malignant history. Nevertheless, it is critical to differentiate a metastatic tumor from primary thyroid lesions, as the clinical management and the prognosis are different for the two entities. More recently, elastosonography opened new possibilities to ultrasound in different fields, such as thyroid nodule differentiation. Herein, we report a case of metastatic signet ring cell carcinoma to the thyroid studied with quantitative elastography and acoustic radiation force impulse imaging.

Metastatic tumour of spermatic cords, epididymis and seminiferous duct from gastric carcinoma.

Metastatic tumour of spermatic cords, epididymis and seminiferous duct from gastric carcinoma has been recently reported but rarely seen.A case of metastatic tumour from gastric carcinoma in a 50-year old man is herein reported. The initial diagnosis was thickening of both spermatic cords. Needle biopsy of the spermatic cord, testicle and epididymis was performed. Pathological findings showed a gastric signet ring cell carcinoma. Thus, double radical orchiectomy was performed and metastatic signet ring cell carcinoma of the spermatic cord and testis was diagnosed through histological xamination and immunohistochemistry. Physicians should be aware that gastric carcinoma is one of the possibilities for metastasis to the seminal duct.

Endobronchial ultrasound‐guided transbronchial needle aspiration diagnosis of mediastinal lymph node metastasis of mucinous adenocarcinoma: Arborizing stromal meshwork fragments as a diagnostic clue

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is a reliable and accurate method for the diagnosis of mediastinal metastases in patients with pulmonary and extrathoracic neoplasms. We report the cytopathologic findings of a case of metastatic signet-ring cell carcinoma with abundant extracellular mucin production in the mediastinal lymph nodes of a 41-year-old woman, who presented with nausea, abdominal pain, and weight loss. Imaging studies showed a renal mass, numerous lung nodules, and mediastinal and retroperitoneal lymphadenopathy. EBUS-TBNA of level 4R and 7 lymph nodes showed abundant, thick, "clean" mucus with entrapped ciliated bronchial cells, rare histiocytes, and fragments of cartilage. No neoplastic cells could be identified in Diff-Quik®-stained smears during the rapid on-site evaluation, but rare signet-ring cells were identified in the Papanicolaou-stained smears and cellblock sections. A distinctive feature of the aspirates was the presence of large branching (arborizing), "spidery" stromal fiber meshwork fragments. These stained metachromatically (magenta) with Romanowsky-type stains and cyanophilic to orangeophilic with Papanicolaou stains and showed occasional attached bland spindle cells, but had no capillary lumina or CD31-staining endothelial cells. The tumor cells were strongly and diffusely positive for CEA, CDX2, CK7, CK20, and MUC2, supporting the diagnosis of a metastatic signet-ring cell adenocarcinoma, most likely of gastrointestinal origin. We believe that the presence of the large spidery stromal fiber fragments is a useful clue to the presence of a mucinous neoplasm in EBUS-TBNA and allows the differentiation of the neoplastic mucus from contaminating endobronchial mucus.

Microangiopathic Hemolytic Anemia as the First Manifestation of Metastatic Signet Ring Cell Carcinoma of Unknown Origin: A Case Report and Review of Literature

Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in some solid tumors, but MAHA accompanied by signet ring cell carcinoma of an unknown origin is very rare. In this study, we present the case of an 80-yr-old man who was admitted to the hospital because of a 1-month history of lower back pain and dyspnea. He was diagnosed with MAHA on the basis of the laboratory findings that revealed anemia with schistocytes, decreased haptoglobin levels, and a negative direct Coombs' test. Bone marrow examination, which was performed because of the progression of anemia, revealed bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis. However, the primary origin of this signet ring cell carcinoma was not found. When the cause of progressive MAHA is unknown, the possibility of cancer-associated MAHA must be excluded by performing additional tumor workup, including the detection of tumor markers, gastric and colorectal endoscopic examinations, bone marrow examinations, and positron emission tomography-computed tomography or bone scans.

Metastatic Signet Ring Cell Carcinoma of the Bilateral Breasts and Ovaries from Gastrointestinal Tract in a Young Breastfeeding Female - A Case Report

We report a case of a metastatic signet ring cell carcinoma (SRCC) of gastrointestinal tract. The case is very rare because gastrointestinal tract SRCC was metastatic to bilateral breasts and ovaries (Krukenberg tumor) in the same young woman almost synchronously under breastfeeding condition. Though the primary site was not detected, IHC results fully verified that the tumor originated from gastrointestinal tract. The severe situation of the patient was believed to be connected to her high estrogen hormone.

Ovarian malignant Mullerian mixed tumor (heterologous) whose epithelial component is composed predominantly of signet ring cell carcinoma

Ovarian malignant Mullerian mixed tumor (MMMT) (carcinosarcoma) is a relatively rare, very aggressive tumor. Herein is presented an unusual case of heterologous MMMT with an epithelial element composed predominantly of signet ring cell carcinoma. A 60-year-old Japanese woman consulted our hospital because of a pelvic mass. Imaging modalities showed a huge tumor of the right ovary. Laparotomy was performed, and frozen section showed a malignant tumor. Therefore, hysterectomy, bilateral salpingo-oophorectomy, lymph node dissection, and omentectomy were performed. On gross examination, the right ovarian tumor was solid, measuring 12 × 13 × 12 cm. The surface was smooth but bosselated. Histologically, the tumor was composed of epithelial and sarcomatous elements. Curiously, the epithelial element was composed predominantly of signet ring cell carcinoma. A small area showed tubular adenocarcinoma and poorly differentiated carcinoma. The sarcomatous element was homologous with spindle cell sarcoma with many mitotic cells. The signet ring cells had mucins. Immunohistochemically, the epithelial element was positive for cytokeratins, EMA, p53, CEA, CA19-9, and Ki-67 (labeling = 75%). The sarcomatous element was positive for vimentin, α-smooth muscle actin, p53, and Ki-67 (labeling = 36%), indicating that it was a leiomyosarcoma. Metastases were found in many lymph nodes and intravascular spaces in the peritoneum; the metastases were composed of epithelial elements. To the best of our knowledge, there have been no descriptions in the English literature of MMMT composed predominantly of signet ring cell carcinoma. An MMMT in this case, should be differentiated from Krukenberg tumor, metastatic signet ring cell carcinoma, and signet ring stromal tumor.

Metastatic signet ring cell carcinoma presenting as a thyroid nodule: Report of a case with fine‐needle aspiration cytology

Metastatic carcinomas to the thyroid are quite rare in daily cytology practice. However, when present they may produce a diagnostic dilemma, particularly when they share some morphologic similarities with primary thyroid lesions and when occurring in patients with occult malignant history. Herein, we report a case of metastatic gastric signet ring cell carcinoma to the thyroid. Our patient presented with an isolated right thyroid nodule, which was clinically considered to be a primary thyroid neoplasm. Fine-needle aspiration (FNA) cytology of the nodule revealed a cellular specimen with cohesive fragments and scattered individual neoplastic cells. The neoplastic cells had enlarged nuclei, fine chromatin, and inconspicuous nucleoli. Nuclear crowding, molding, and grooving were prominent. Intranuclear inclusion-like clearance was identified. Some tumor cells also had eccentric nuclei, creating a signet ring cell appearance. The colloid was scant. These cytological features may be seen in cases of papillary thyroid carcinoma or signet ring cell follicular adenoma; however, the presence of the signet ring cells is unusual in primary thyroid lesions and raises the possibility of a metastatic lesion to the thyroid. In our case, the tumor cells were positive for AE1/AE3, mucicarmine, and periodic acid-Schiff, but negative for thyroglobulin and thyroid transcription factor-1. The patient was also found to have a 3.7-cm mass in the distal esophagus/proximal stomach. Biopsy of this mass showed an invasive signet ring cell carcinoma. The purpose of our study is to discuss the cytological features and the differential diagnosis of this unusual thyroid FNA case.

Occult gastric signet ring cell carcinoma presenting as spermatic cord and testicular metastases: “Krukenberg tumor” in a male patient

Krukenberg tumor is a well-known ovarian metastasis, usually of gastric signet ring cell carcinoma in female patients. Although gastric carcinoma is more frequent in men, to our knowledge, only few cases of counterpart testicular metastases have been described as yet. We report a 64-year-old patient who complained of right testicular pain. Right-sided orchiectomy was performed, and metastatic signet ring cell carcinoma of spermatic cord and testis was diagnosed through histological examination and immunohistochemistry. The following stomach biopsy confirmed the primary signet ring cell carcinoma in the stomach. This extremely rare form of metastatic dissemination resembles the Krukenberg tumor of ovaries. Immunohistochemical staining plays an important role in the differential diagnosis of spermatic cord enlargement.

Signet-ring stromal tumor of the testis: a case report and literature review

Primary signet-ring stromal tumor of the testis is extremely rare. To our knowledge, only one case has been reported in the literature. Herein, we present a case of testicular signet-ring stromal tumor with positive immunostain for CD99, which has not been reported previously. We also review the literature and discuss the clinicopathological significance of this type of tumor. The most important differential diagnosis of signet-ring stromal tumor is metastatic signet-ring cell carcinoma because of its different management and prognosis. Fortunately, signet-ring stromal tumors have a well-defined growth pattern, bland histological features, no mucin production, and immunoreaction to vimentin rather than cytokeratin, all of which help pathologists to rule out metastatic adenocarcinoma. Although ovarian signet-ring stromal tumors are categorized in the fibroma/thecoma group of sex cord stromal tumors, the cell origin of signet-ring stromal tumors is still debatable. The histological criteria for predicting clinical behavior of signet-ring stromal tumors are not clear. Fortunately, however, all reported signet-ring stromal tumors are benign tumors with excellent prognosis, and they do not recur or metastasize. We consider signet-ring stromal tumor to be a special type of sex cord stromal tumor.

Mucin-producing signet ring cell adenoma of the thyroid

Signet ring cell adenoma of the thyroid, though rare, is well documented. This change is chiefly due to intracellular accumulation of thyroglobulin that appears mucinous. Awareness of this entity is important as it may closely simulate a metastatic mucin-secreting signet ring cell carcinoma. Although the mucinous material in signet ring cells has been reported to stain positive with thyroglobulin, in some cases it may not be so. We herein describe a rare case of a 46-year-old man who was hypothyroid and the mass removed from the thyroid showed a mucin-producing signet ring cell adenoma of the thyroid.

Pulmonary tumor thrombotic microangiopathy resulting from metastatic signet ring cell carcinoma of the stomach

Pulmonary tumor thrombotic microangiopathy is an unusual malignancy-related respiratory complication characterized by multiple microthrombi and intimal myofibroblast proliferation. Its clinical manifestation is subacute respiratory failure with pulmonary hypertension. Herein is reported a case of pulmonary tumor thrombotic microangiopathy associated with gastric signet ring cell carcinoma. A 51-year-old woman with gastric cancer died of subacute respiratory failure. Autopsy showed gastric signet ring cell carcinoma with diffuse metastasis of pulmonary lymphatics and pleurae; every organ examined lacked a space-occupying tumor mass. Histologically, proliferated intimal myofibroblasts obliterated most of the pulmonary vascular lumen, and a few stenosed vascular lumina contained cancer cells. In addition, pulmonary vasculature associated with intimal proliferation contained microthrombi. Most cancer cells in the stomach and pulmonary lymphatics were typical signet ring cells, whereas those in vascular lesions were cells of poorly differentiated adenocarcinoma without mucous production. Consistent with a previous report, the latter expressed vascular endothelial growth factor (VEGF) and tissue factor (TF). The proliferated intimal myofibroblasts also expressed type 2A serotonin receptor (5-HT(2A)). These findings suggest that local expression of VEGF, TF, and 5-HT(2A) may be linked to the pathogenesis of this unusual pulmonary complication.

A Case of Gastric Adenocarcinoma Presenting as Meningeal Carcinomatosis

Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. The most common cancers involving the leptomeninges are breast, lung cancer and melanoma. However, gastric adenocarcinoma has been rarely reported with leptomeningeal carcinomatosis. The presenting manifestations are usually headache, visual disturbances and seizures. We report a case of leptomeningeal metastasis that presented as a gastric cancer. A 49-year-old woman was admitted to our hospital with the symptoms of headache and melena for 10 days. The endoscopy showed a thickening of the folds of the stomach compatible with the diagnosis of a Borrman type IV gastric cancer. The biopsy revealed a signet ring cell carcinoma. The MRI of brain showed no abnormal findings; however, the patient complained of an intractable persistent headache, nausea and vomiting on admission day 6. The cytology examination of the cerebrospinal fluid supported the diagnosis of metastatic signet ring cell carcinoma.

A Case of Metastatic Signet Ring Cell Carcinoma of the Colon in a Child

A Case of Metastatic Signet Ring Cell Carcinoma of the Colon in a Child

Mucin Profiles in Signet-ring Cell Carcinoma

Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas. To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (<5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (>50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1.2.4.5.6v, MUC2.4+/MUC5v/ MUC1.6-, and MUC1+/MUC2.5.6v/MUC4-, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries. Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.

Clinicopathologic Analysis of Solid Papillary Carcinoma of the Breast and Associated Invasive Carcinomas

Solid papillary carcinomas (SPCs) are uncommon tumors composed of circumscribed large cellular nodules separated by bands of dense fibrosis. The aim of this study was to further elucidate the characteristics of SPC, the types and significance of invasive carcinomas associated with these tumors, and the long-term clinical outcome. Fifty-eight SPCs were analyzed (mean follow-up, 9.4 years). Cases were divided into three groups: 1) SPC only (32.7%), 2) SPC with extravasated mucin (8.6%), and 3) SPC with invasive components (58.7%) consisting of neuroendocrine-like (29.5%), colloid (23.5%), ductal not otherwise specified (14.5%), lobular (3%), tubular (3%), or mixed (26.5%). The mean age was 72 years. All were estrogen receptor positive and 86% were histologic grade 1. The total size of the tumor measured 0.3 to 15 cm. In the group with invasive carcinoma, the size of invasion was 0.1 to 4 cm. Axillary nodes were involved in 13% of the cases (6 of 46); all of these had an invasive component in the primary tumor. Local recurrence was seen in 5 patients, all from the group with invasive carcinoma. Overall, 11.7% died of their tumor, 1 to 4 years after diagnosis (mean, 2.3 years); none of them belongs to the group of noninvasive SPC. Five of the 6 patients who died of tumor had invasive components. The sixth patient who died with "metastatic signet-ring cell carcinoma" at 10 years was in the group of patients with SPC with extravasated mucin where the SPC lesion had prominent signet-ring cell features. In conclusion, SPCs are heterogeneous lesions that arise in older women and have an indolent behavior. Lymph node and distant metastases are uncommon and generally limited to cases with (conventional) invasive components.