Metastatic Signet Ring Cell Adenocarcinoma Research Articles

S4153 Metastatic Signet Ring Cell Adenocarcinoma Manifesting as Chronic Leg Pain

S4153 Metastatic Signet Ring Cell Adenocarcinoma Manifesting as Chronic Leg Pain

An interesting case of gastric adenocarcinoma presenting as bicytopenia in young adult

Abstract A 28-year-old male with no prior comorbidities came with chief complaints of loss of weight for 4 months, generalised weakness for 1 month and blackish discolouration of stools for 20 days. On general examination, pallor present; rest of the physical examination was normal. Laboratory investigations showed low haemoglobin (4.8 g/dL) and platelet count (10,000/mm3). Atypical cells were present in the peripheral blood smear and accounted for 4%. packed red blood cells and platelet-rich plasma transfusions were given. As the blood counts were not improving, bone marrow aspiration and biopsy were done which showed metastatic signet-ring cell carcinoma. In view of melaena, endoscopy was done, which showed carcinoma stomach with active bleeding. The patient was diagnosed to have metastatic signet-ring cell adenocarcinoma with bone marrow metastasis. In view of the advanced nature of disease, the patient was given palliative and supportive treatment.

Large Pleural Effusion Secondary to Primary Signet-Ring Cell Adenocarcinoma of the Lung

Primary signet-ring cell adenocarcinomas (SRCA) that occur outside the gastrointestinal tract are rare with few cases reported in the literature. They carry a poor prognosis and can be a challenge to diagnose. In this case report, we present the case of a 69-year-old female who presented to our hospital with a large left-sided pleural effusion. The findings seen on histopathology and immunohistochemistry (IHC) staining of the pleural fluid were consistent with primary signet-ring cell adenocarcinoma of the lung, and further investigations excluded a secondary source of malignancy.To the best of our knowledge, this is the first reported case of pleural effusion without an underlying lung mass diagnosed as primary signet-ring cell adenocarcinoma of the lung. Given how rare primary signet-ring cell adenocarcinoma of the lung is, it is important for physicians to carry out a comprehensive diagnostic workup to differentiate between primary and metastatic signet-ring cell adenocarcinoma as this will determine prognosis and treatment.

PD-L1 Expression Predicts a Distinct Prognosis in Krukenberg Tumor with Corresponding Origins.

Krukenberg tumor (KT) is an uncommon ovarian metastatic signet-ring cell adenocarcinoma that mostly metastasizes from gastrointestinal carcinoma. Optimal treatment options for KTs are limited. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have shown remarkable activity in clinical trials for metastatic tumors. Here, we evaluated PD-L1 expression and T cell infiltration in KTs and their corresponding primary tumors. Positive tumor PD-L1 expression was detected in 9 (25.7%) KTs from gastric carcinomas (GCs) and in 20 (66.7%) KTs from colorectal carcinomas (CRCs). Patient survival was assessed according to the PD-L1 status and CD8+ T cell density. Positive tumor PD-L1 expression in KTs from GCs was associated with poor prognosis. In contrast, positive tumor PD-L1 expression in KTs from CRCs was associated with an improved prognosis. We analyzed copy number variations of the PD-L1 gene in KTs. PD-L1 expression was higher in cases with copy number gains. The T cell densities within KTs and their corresponding primary tumors were compared. The densities of CD8+ T cells correlated significantly between the primary tumors and KTs from the same case. Taken together, the research further highlighted targets for immune-based therapy in KTs from GCs and CRCs.

Microangiopathic Hemolytic Anemia in Metastasized Signet Ring Cell Carcinoma: A Report of Three Cases

Systemic manifestations of gastric cancer related to paraneoplastic phenomena are rarely seen at initial presentation. We report three patients who presented with microangiopathic hemolytic anemia (MAHA) with initial symptoms of metastatic signet ring cell adenocarcinoma.

Aggressive Microangiopathic Hemolytic Anemia Associated with Metastatic Signet Ring Cell Adenocarcinoma of the Colon: A Note of Caution Prior to Surgical Intervention

Purpose: Microangiopathic hemolytic anemia (MAHA) is a microvascular hypercoagulable state characterized by Coombs-negative fragmentation hemolysis of red blood cells associated with thrombocytopenia and a propensity for bleeding. Cancer-related MAHA is a recognized clinical entity that portends a poor prognosis as compared to patients without MAHA. Here, we report a patient with metastatic signet cell adenocarcinoma (SCA) of the sigmoid colon complicated by MAHA and disseminated intravascular coagulation (DIC) after primary resection for recurrent tumor bleeding. A 59-year-old man presented with persistent anorexia and hematochezia. Computed tomography revealed a 6-cm mass in the sigmoid colon with metastatic disease to the liver. Colonoscopy revealed a mass 23 cm into the sigmoid. Biopsies showed carcinoma with signet-ring features. Liver biopsy confirmed metastatic adenocarcinoma. Systemic chemotherapy was not felt to be appropriate at the time of diagnosis, given the risk of poor wound healing with chemotherapy, thrombocytopenia, and impaired liver function. A sigmoid resection was performed with seven out of seven lymph nodes positive for metastatic disease. Postoperatively, the patient developed an extraperitoneal hematoma, requiring intraoperative drainage. In addition to refractory anemia, the patient developed several laboratory derangements, including low fibrinogen levels (142 mg/dL) and thrombocytopenia, (platelet 30K/μL) despite repeated transfusions, hyperbilirubinemia (T. bili 48.2 mg/dL), elevated alkaline phosphatase (613 unit/L), fibrin split products (>20 mg/dL), and marked coagulopathy. The patient was subsequently transferred to a tertiary care institution, where the diagnosis of MAHA was made after peripheral smear evaluation confirmed the presence of schistocytosis. Despite aggressive transfusion support, the patient remained clinically unstable, preventing initiation of systemic chemotherapy. Given his continued deterioration, a more palliative approach was undertaken. MAHA is exceedingly rare in patients with SCA. However, our case and prior reports suggest that patients with advanced disease who undergo surgical manipulation before chemotherapy may be more likely to develop MAHA and DIC. This could be a result of disruption of abnormal blood vessels supplying the tumor and subsequent release of tumor-induced metabolites like mucin, triggering alterations in hemostasis. Therefore, we propose that neoadjuvant chemotherapy be considered prior to surgical resection, especially in patients with advanced disease at the time of diagnosis; however, a larger number of patients with this phenomenon would be required to draw clear clinical recommendations.

26. Unusual adenomatoid tumour of the ovary consisting entirely of signet ring like-cells mimicking metastatic signet ring cell adenocarcinoma

Adenomatoid tumours of the ovary are rare benign neoplasms of mesothelial origin. They usually present as microscopic incidental findings in ovaries removed for other pathology. They are usually located within the ovarian hilum and tend to have a characteristic morphology of bland flattened to epithelioid cells with eosino-philic cytoplasm that are arranged into tubules, trabeculae and mi-crocystic spaces. We present an unusual case of an adenomatoid tumour arising wholly within the cortex of the ovary and consisting of entirely of infiltrative nests and small tubule-like structures composed of cells with a signet ring-like morphology. The im-munohistochemical profile of these cells was strong keratin posi-tivity and only weak, patchy staining for the mosethelial marker calretinin. The combination of these morphologic and immunohis-tochemical features could, under certain clinical conditions, particularly if a panel of appropriate immunohistochemical stains are not performed, lead to the over diagnosis of these benign tumours as metastatic signet ring cell adenocarcinoma. In view of the findings from our case, when considering a diagnosis of metastatic signet ring cell adenocarcinoma in the ovary, close attention must be paid to the cellular and nuclear features as well as the cytoplas-mic vacuoles to ensure that the diagnosis of adenomatoid tumour is not missed. We would also recommend using WT-1 and D2–40, in addition to calretinin, as additional evidence of mesothelial origin in a panel of immunohistochemical stains.

Signet Ring Cell of the Non-Neoplastic Endometrium: A Case Report and Literature Review

The observation of signet ring cells in endometrial biopsy results raises the possibility of the existence of a malignant primary or metastatic adenocarcinoma. We describe the case of a middle aged woman whose endometrial biopsy and curettage specimens contained signet ring cells indicating stromal decidual changes. Positive cytokeratin and CD10 immunohistochemistry staining results were revealed in the signet ring cells, features favoring a diagnosis of endometrial stromal cells showing decidual changes rather than a primary or metastatic endometrial neoplasm. Upon immunohistochemistry evaluation, they presented as vacuolated, decidualized endometrial stromal cells. Awareness of this morphologic change in the endometrial stroma can prevent overdiagnosis and overtreatment as primary or metastatic signet ring cell adenocarcinoma. Recognized by this morphologic feature, signet ring cells, or their close mimics, should not always be considered as a high grade or poorly differentiated adenocarcinoma. doi: http://dx.doi.org/10.4021/jcgo42e

Metastatic signet ring cell adenocarcinoma of the bladder: responsive to treatment?

Signet ring cell variant of mucinous adenocarcinoma of the urinary bladder is an exceptionally rare urologic malignancy, generally felt to be resistant to chemotherapy and radiotherapy. We describe a case of this malignancy with unusual sites of metastasis and an unexpectedly good response to treatment.

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.

Fine‐needle aspiration diagnosis of metastatic intestinal‐type sinonasal adenocarcinoma

Fine-needle aspiration biopsy is a reliable and accurate method for the diagnosis of nodal metastases of head and neck cancers. We report the cytopathologic findings of a case of metastatic sinonasal intestinal type adenocarcinoma (ITAC) in a 58-year-old man who presented with enlarged cervical lymph nodes on a follow-up imaging study, 5 months after resection of a sinonasal ITAC. Ultrasound-guided fine needle aspiration of the station 2B lymph node yielded moderately cellular smears with abundant background mucin pools, numerous naked, atypical nuclei, and rare cells with signet ring cell morphology. Rare mitoses, apoptotic bodies, and necrotic debris were also present. Occasional clusters of signet ring cells were also seen in the cell block sections. Immunoperoxidase stains showed these cells to be positive for CK20 and villin. The differential diagnosis included a metastatic signet ring cell adenocarcinoma from the gastrointestinal tract and a metastatic sinonasal ITAC. Review of the previously resected sinonasal ITAC revealed a similar morphology with signet ring cells and abundant extracellular mucin production; the immunostaining results were also similar to those obtained on previously resected sinonasal ITAC. This case emphasizes the importance of considering primary head and neck tumors with intestinal phenotype and immunophenotype in the differential diagnoses of cervical lymph node metastases with signet ring cell morphology.

Diagnostic difficulties and pitfalls in rapid on-site evaluation of endobronchial ultrasound guided fine needle aspiration

Background:One of the novel techniques utilizing fine needle aspiration (FNA) in the diagnosis of mediastinal and lung lesions is the endobronchial ultrasound (EBUS)-guided FNA. In this study, we describe five cases which had a discrepancy between on-site evaluation and final diagnosis, or a diagnostic dilemma when rendering the preliminary diagnosis, in order to illustrate some of the diagnostic difficulties and pitfalls that can occur in EBUS FNA.Methods:A total of five EBUS FNA cases from five patients were identified in our records with a discrepancy between the rapid on-site evaluation (ROSE) and final diagnosis, or that addressed a diagnostic dilemma. All of the cases had histological confirmation or follow-up. The cytomorphology in the direct smears, cell block, and immunohistochemical stains were reviewed, along with the clinical history and other available information.Results:Two cases were identified with a nondefinitive diagnosis at ROSE that were later diagnosed as malignant (metastatic signet-ring cell adenocarcinoma and metastatic renal cell carcinoma (RCC)) on the final cytological diagnosis. Three additional cases were identified with a ROSE and final diagnosis of malignant (large cell neuroendocrine carcinoma (LCNEC) and two squamous cell carcinomas), but raised important diagnostic dilemmas. These cases highlight the importance of recognizing discohesive malignant cells and bland neoplasms on EBUS FNA, which may lead to a negative or a nondefinitive preliminary diagnosis. Neuroendocrine tumors can also be difficult due to the wide range of entities in the differential diagnosis, including benign lymphocytes, lymphomas, small and nonsmall cell carcinomas, and the lack of immunohistochemical stains at the time of ROSE. Finally, the background material in EBUS FNAs may be misleading and unrelated to the cells of interest.Conclusions:This study illustrates the cytomorphology of five EBUS FNA cases that address some of the diagnostic challenges witnessed while examining these specimens during ROSE. Many of the difficulties faced can be attributed to the baseline cellularity of the aspirates, the bronchial contamination, the difficulty identifying neoplasms with bland cytology, the wide spectrum of diseases that can occur in the mediastinum with overlapping cytomorphologic features, the mismatch between the background material and the cell populations present, and the overall unfamiliarity with these types of specimens.

A Case of Bladder Cancer Found during a Workup for Urge Incontinence

Irritative urinary symptoms may suggest the possibility of bladder cancer. We report a case of metastatic bladder cancer that was discovered during a workup for urge incontinence in a 65-year-old woman with a history of stomach cancer. She had a medical history of gastrectomy due to stomach cancer 4 years previously. The patient complained of urgency unresponsive to anticholinergic therapy. Cystoscopy revealed the presence of suspicious bladder mucosal lesions that were biopsied. The pathology was consistent with metastatic signet-ring cell adenocarcinoma. This case suggests that irritative urinary symptoms can be the first clinical manifestation in patients with bladder cancer.

Cystic Lymphangioma-like Adenomatoid Tumor of the Adrenal Gland: Case Presentation and Review of the Literature

Adenomatoid tumors (AT) are usually found in the genital tract of both sexes. They are very rarely located in extragenital sites, and are exceedingly rare in the adrenal. AT of the adrenal gland (AT-AG) are nonfunctioning, usually discovered incidentally and confused on imaging with other more common adrenal neoplasms. The overwhelming majority occur in males. Thirty-four cases have been reported so far, more often presenting grossly as solid tumors, rarely as solid with cystic areas, and 5 cases were almost entirely cystic. At histology they can be either circumscribed or locally infiltrative, and may pose diagnostic difficulties when the pathologist relies on morphology alone or is challenged on frozen section. On light microscopy the diagnosis may be very difficult if the tumor is rich in vacuolated cells, mimicking metastatic signet ring-cell adenocarcinoma. Immunophenotyping and/or electron microscopy are paramount in helping to ascertain their mesothelial lineage. Lymphangioma is the main histologic mimic of solid-cystic and cystic AT-AG, but lymphangioma is immunopositive for endothelial markers and negative for cytokeratins and mesothelial markers. Ultrastructural analysis has been performed in 10 published cases of AT-AG, in all of which the classical microvilli of coelomic type were always observed. In brief we report herein the sixth case of cystic lymphangioma-like AT, which was incidentally discovered during clinical follow-up in a 39-year-old man undergoing cancer staging and surveillance after surgery. The adrenal tumor was 5.5 cm in size and was fully investigated immunohistochemically and ultrastructurally. A complete review of the literature is also presented.

Metastatic signet ring cell adenocarcinoma of bone marrow with bilateral ovarian masses: a case report

We present a case of metastatic signet ring cell adenocarcinoma of bone marrow with radiologically proven bilateral ovarian masses in a 50 year old Asian Indian female. Even after thorough search no extraovarian primary site could be found. Based on overall clinicopathologic correlation, a diagnosis of metastatic signet ring cell adenocarcinoma of bone marrow with uncertain primary was established.

Papillary adenocarcinoma gallbladder with simultaneously detected bilateral ovarian metastases: A Case Report

Gallbladder and bile ducts are rare sources of metastatic tumor in the ovary. There are few reports of a primary tumor in the gallbladder with bilateral ovarian involvement discovered simultaneously. Herein, we report a case of 38 year old female, presenting with symptoms of gallbladder mass, and on Magnetic Resonance Imaging ovarian masses were also detected. A gallbladder carcinoma with Krukenberg tumor involving bilateral ovaries was suspected. Histopathological examination of the resected specimen revealed a papillary adenocarcinoma gallbladder with tumor of similar histology in both ovaries. No signet ring cells were seen on microscopic examination in any of the involved sites. “Krukenberg tumors” by definition, are metastatic signet ring cell adenocarcinoma of the ovary. They are usually bilateral, characterized grossly by solid multinodular enlargement of ovaries and microscopically by diffuse infiltration by signet ring cells, which should occupy at least 10% of the neoplasm, and contain abundant neutral and acidic mucin. Hence, bilateral ovarian metastasis, as in our case, is not always a Krukenberg tumor at the histological level.

Vesical metastasis of gastric adenocarcinoma

Metastatic vesical tumors are rare, and constitute approximately 1% of all neoplasias affecting this organ. The authors report the case of a 63-year old woman with vesical metastasis of gastric adenocarcinoma. Patient presented signs of cachexia and complained of left lumbar pain and dysuria unresponsive to antibiotic therapy for approximately 5 months. She reported a previous partial gastrectomy due to ulcerative undifferentiated gastric adenocarcinoma 1 year and 9 months before. Cystoscopy revealed an extensive vegetative lesion in bladder, occupying its entire mucosal surface. The biopsy revealed metastatic signet-ring cell adenocarcinoma.

A Solitary Cutaneous Nodule Revealing Signet-Ring Cell Adenocarcinoma-A Case Report and Literature Review

Signet ring cells are formed by intracytoplasmic accumulations of various substances that push the nucleus to the cellular border. Signet ring cells are regarded as evidence of adenocarcinoma, and in the cutaneous region, they often indicate a metastatic lesion from a visceral organ. Here we report a case of metastatic signet ring cell adenocarcinoma in a 56-year-old male present as a solitary cutaneous nodule without evidence of a visceral origin at the beginning, but an occult gastric adenocarcinoma was proved finally. The pathological characteristics and management are described and the previous literatures are also reviewed.

Adenocarcinoma of the Uterine Cervix with Massive Signet-Ring Cell Differentiation

Primary signetring cell adenocarcinoma of the cervix is very rare and less common than metastatic signet-ring cell adenocarcinoma. To the best of the authors' knowldge only one genuine case has been reported to date. Tvvo cases of primary signeting cell adenocarcinoma of the uterine cervix in patients aged 68 and 74 years are presented. The tumors were in stage IB. The light microscopic findings were conirmed by histochemical and immunohistochemical study. DNA nuclear analysis by flow cytometry of the neoplasms revealed an aneuploid (tetraploid) pattern. The paients had no evidence of recurrent or metastatic disease 35 and 25 months after a radical hysterectomy with bilateral salpingo-oophorectomy and lymph node dissecion respectively. Primary signet-ring cell adenocarcinoma of the cervix should be diferentiated from metastatic adenocarcinoma, endocervical involvement by signeting cell carcinoma of the endometrium, benign mucinfilled signet-ring cell aggregates that may accumulate in mucosal folds, microglandular hyperplasia, muciarminophilic histiocytosis, and other malignant neoplasms that may have signet ringlike cells and deserve consideration such as squamous cell carcinoma, maligant lymphoma, myeloma, and malignant melanoma. Although very rare, signeting cell adenocarcinoma of the cervix can exist as a primary tumor. Distinction beween a primary neoplasm and a metastasis to the cervix is decisive for treatment and prognosis.

Metastatic Signet-Ring Cell Adenocarcinoma to the Urinary Bladder

Gastric signet-ring carcinoma can metastasize to unusual sites.Occult cardiac metastasis, disseminated cutaneous lesions without involvement of internal organs, secondary prostatic involvement, and breast metastasis have all been described (1-4). We were able to find only 4 reported cases of metastatic signet-cell adenocarcinoma to the urinary bladder, three of which were found in the Japanese literature. We report a case of gastric signet-ring adenocarcinoma with bladder metastasis.