Metastatic Anaplastic Carcinoma Research Articles

TO STUDY THE ETIOPATHOLOGICAL SPECTRUM OF ADULT PATIENTS WITH PANCYTOPENIA

Background: Pancytopenia is diagnosed when there is a reduction in all three hematopoietic cell lines. Till date there is limited number of studies on the frequency of various causes of pancytopenia. Of these some have been reported from the Indian subcontinent. There appears to be a changing spectrum of pancytopenia over the past two decades. The objective was to study the etiopathological spectrum of adult patients with pancytopenia over a period of one and half year.
 Methods: The Prospective and retrospective observational study was conducted in the Department of Family Medicine, Batra Hospital and Medical Research Centre, New Delhi. A total of 120 Patients were included in the study. All patients gave their consent to take part in the study and were subjected to a questionnaire regarding symptoms, past relevant history, lifestyle and detailed clinical examination and investigations as mentioned in materials and methods.
 Results: Six broad diagnostic groups could be identified in adults with pancytopenia. Megaloblastic anemia (D1) was the largest group comprising 57.5% of all patients. 11.7% of patients with pancytopenia were diagnosed as Aplastic anemia (D2).11.7% of patients with pancytopenia were diagnosed as leukemia/lymphoma (D3) such as lymphoma (1), metastatic anaplastic carcinoma (1), acute leukemia (11), and metastatic gastric carcinoma (1). 15% of patients with pancytopenia were diagnosed with infections (D4) such as complicated malaria cases (7), HIV (5), disseminated tuberculosis (4), viral (2). We also encountered (D5) 0.8% was Myelophthisis/Storage disorder as myelodysplastic syndrome (1) and 3.3% were other (D6) as reactive marrow (4).
 Conclusion: Pancytopenia is not a disease itself. It is a hematological feature of varying etiology with slight male preponderance. Megaloblastic anemia along with mixed nutritional anemia is leading cause of pancytopenia in India followed by infections being second and aplastic anemia and acute leukemia being third common causes.
 Keyword: Pancytopenia, Megaloblastic anemia, Nutritional anemia.

Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype.

BackgroundBreast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation.MethodsCells were continuously exposed to low-level cadmium (2.5 μM) and checked in vitro and by xenograft study for signs of malignant transformation. Transformant cells were molecularly characterized by protein and transcript analysis of key genes in breast cancer.ResultsOver 40 weeks of cadmium exposure, cells showed increasing secretion of matrix metalloproteinase-9, loss of contact inhibition, increased colony formation, and increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated cells into mice produced invasive, metastatic anaplastic carcinoma with myoepithelial components. These cadmium-transformed breast epithelial (CTBE) cells displayed characteristics of basal-like breast carcinoma, including ER-α negativity and HER2 (human epidermal growth factor receptor 2) negativity, reduced expression of BRCA1 (breast cancer susceptibility gene 1), and increased CK5 (cytokeratin 5) and p63 expression. CK5 and p63, both breast stem cell markers, were prominently overexpressed in CTBE cell mounds, indicative of persistent proliferation. CTBE cells showed global DNA hypomethylation and c-myc and k-ras overexpression, typical in aggressive breast cancers. CTBE cell xenograft tumors were also ER-α negative.ConclusionsCadmium malignantly transforms normal human breast epithelial cells—through a mechanism not requiring ER-α—into a basal-like cancer phenotype. Direct cadmium induction of a malignant phenotype in human breast epithelial cells strongly fortifies a potential role in breast cancer.

A RARE CASE OF LARGE CELL CARCINOMA IN A PATIENT WITH DERMATOMYOSITIS.

Background Dermatomyositis (DM) is an idiopathic inflammatory myopathy. Like polymyositis (PM), it is a rare disorder with prevalence rates estimated at about 1 per 100,000 in the general population. There is a female to male predominance of about 2:1 in adults. The peak occurs in the fifth decade, although all age groups may be affected. DM (and PM to a lesser extent) has been known to be associated with cancer. Estimates of the frequency of cancer in adults with DM/PM range from 7 to 34%. There have been several reports of improvement of myositis following successful treatment of the malignancy, as well as worsening of the myositis associated with cancer recurrence. So far, very few cases of large cell carcinoma associated DM have been reported. Case Report We present a case of a 50-year-old gentleman who presented to us with generalized worsening pain and stiffness for 2 months. He also noticed a rash on the elbows and knuckles, which had appeared since the onset of increasing stiffness. Positive laboratory values: ESR 38, AST/ALT 333/104, LDH 715, CK 28,258, TSH 2.4, ANA positive (1:160 speckled pattern), aldolase 34.4 (normal 0-7). A CT scan of the chest was performed in view of the diagnosis of dermatomyositis. There was a 4.2 cm by 3 cm retrocaval mass with areas of necrosis and few mediastinal lymph nodes. There was a filling defect in the right pulmonary artery with recanalization suggestive of a chronic pulmonary embolus with multiple pleural-based wedge-shaped densities suggestive of pulmonary infarcts. A biopsy of the mediastinal lymph nodes revealed a metastatic anaplastic carcinoma of the large cell type. The patient received chemotherapy with carboplatin and docetaxel and radiotherapy, anticoagulation for pulmonary embolism, and steroids for DM. Discussion DM, a rare disorder of the dermatologic and musculoskeletal system, is often the harbinger of malignancy. A systematic search for occult malignancy should be carried out in patients diagnosed with DM. Mortality is due to progression of underlying malignant disease. This underscores the potential harmful effects of delayed diagnosis of malignancy in patients with DM. Investigations may include CT scans of the chest, abdomen, and pelvis, along with endoscopy of the gastrointestinal tract. Investigations of the genitourinary tracts and breast may be undertaken depending on individual cases.

Metastatic Anaplastic Carcinoma of the Small Intestine Arising from The Lung

A metastatic carcinoma of the small intestine is rare. Here, the case study of an 80-year-old lung carcinoma patient, with generalized peritonitis due to neoplastic perforation of the small intestine is reported. Pathological studies of a small intestinal mass revealed a metastatic anaplastic carcinoma arising from the lung. Patients with known lung carcinoma, who develop abdominal complaints, should be examined thoroughly. Although it is very difficult to diagnose and treat a metastatic carcinoma of the small intestine, in our judgment, with a greater awareness of this neoplasm, more cases may be diagnosed in the early stages, leading to improved rates of survival.

Fine needle aspiration cytology, histology and immunohistochemistry of anaplastic large cell Ki-1-positive lymphoma. A report of three cases.

Large cell anaplastic Ki-1 lymphoma is a cytologically undifferentiated malignant lymphoma that needs to be distinguished from a variety of other neoplasms using immunohistochemistry. The cytopathologic, histopathologic and immunohistochemical features of three cases of Ki-1-positive anaplastic large cell lymphoma are presented. The patients comprised two females and one male, ranging in age from 48 to 82 years. Presentation was with peripheral lymphadenopathy. Fine needle aspiration biopsy of an enlarged lymph node in each case revealed single cells and poorly cohesive groups of cells with large, pleomorphic nuclei, many containing prominent nucleoli, and a moderate amount of cytoplasm. Many binucleate and multinucleate tumor cells were present. In each case the cytologic features suggested metastatic anaplastic carcinoma. The histopathologic features of excised nodes were also suggestive of this diagnosis, with cohesive groups of cells and many multinucleate tumor giant cells. In one case malignant cells were confined to subcapsular and medullary sinuses, further highlighting the resemblance to metastatic carcinoma. Immunohistochemical staining of histologic sections confirmed the diagnosis of large cell anaplastic, Ki-1-positive lymphoma, with the tumor cells in the three cases showing diffuse and strong positive staining for Ki-1 antigen. Further immunohistochemistry revealed tumor cells in two cases to be positive for leukocyte common antigen, two cases to express B-cell markers and one case to express T-cell markers. The fine needle aspiration biopsy findings confirmed that large cell anaplastic, Ki-1-positive lymphoma should be considered in the cytologic differential diagnosis of anaplastic tumor within a lymph node. The differential diagnosis may include anaplastic carcinoma, malignant melanoma, sarcoma, Hodgkin's disease and histiocytic lymphoma. Immunostaining of fine needle aspiration biopsy material or, preferably, of histologic tissue sections is necessary for confirmation of the diagnosis.

Radiation therapy of canine brain masses.

This article evaluates the responses of 14 dogs with brain masses using orthovoltage irradiation for definitive treatment. Dogs were anesthetized for computed tomography (CT) examination, formation of head immobilization and positioning devices, radiation treatment simulation, and treatments. Total doses of 39 Gy (9 dogs) or 45 Gy (5 dogs) to the tumor were administered over 25 to 41 days. Two or three portals (parallel opposed lateral with or without a dorsal field) were used. Treatment volumes included the tumor and peritumoral edema, as determined by CT scan, and a 1-cm margin. Histopathologic diagnoses were available in 9 of 14 dogs. There were 4 meningiomas, 1 lymphosarcoma, 1 pituitary adenoma, 1 metastatic anaplastic carcinoma, 1 anaplastic oligodendroglioma and 1 dog with granulomatous meningoencephalitis. At the end of radiation therapy, 10 dogs could be evaluated for progression of clinical signs: 3 dogs deteriorated or failed to improve, and 7 dogs improved. At the time of analysis, all dogs were dead. Mean and median survival times, measured from the beginning of radiation, were 345 and 489 days, respectively. This was compared with mean survival times of 30 to 81 days reported in the literature for dogs with brain tumors that did not receive treatment. The median survival time of 9 dogs treated with 39 Gy was 153 days, versus 519 days for 5 dogs that received 45 Gy. It appears that radiation therapy prolongs survival times for dogs with brain masses. Although megavoltage therapy would be optimal, orthovoltage radiation can be applied in total doses of 45 Gy in 3.75 Gy fractions over 28 days without adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Observer variation in the pathologic diagnosis of malignant lymphoma in Canada.

Biopsies from "poor prognosis" non-Hodgkin's lymphomas were studied to assess diagnostic variations among pathologists. The original diagnosis and the diagnoses of a nationwide panel of local reference pathologists (LRPs) from 104 cases were reviewed and the technical quality of each biopsy evaluated. Using a modified Rappaport classification, there was agreement in 57% of cases among the panel. This increased to 84% when diagnoses were grouped according to Working Formulation grades. Of the 90 cases in which a comparison of the contributing pathologist's diagnosis and the most common panel diagnosis was possible, there was exact agreement in 51% (kappa = 0.311) of cases and agreement regarding WF grade in 68% (kappa = 0.318). Major panel disagreements occurred in 26 (25%) cases, involving the distinction of metastatic anaplastic carcinoma or Hodgkin's disease from non-Hodgkin's lymphoma in 17 cases and follicular versus diffuse architecture in 16 (overlap present). The contributing pathologist had a major disagreement with the panel in 18 cases (20%), of type and frequency similar to those within the panel itself. Poor fixation (complete or partial) was present in 49 cases (47%); this resulted in significantly fewer majority agreements than in the well-fixed group (25% versus 60%, P = 0.020) and also increased rates of disagreement in the diagnosis of lymphoma versus anaplastic carcinoma. Thus improvements in the technical quality of biopsy material could further improve the diagnostic accuracy of lymphoma diagnosis.

Prolonged survival following cerebral metastasis from pulmonary cancer

A case is reported of prolonged survival after pneumonectomy for anaplastic carcinoma of the left lung and excision of metastatic anaplastic carcinoma of the brain. The patient has survived for 8 years, 6 months after the lung surgery and 7 years after the brain surgery.