Intravascular Invasion Research Articles

A Rare Case of Classic Testicular Seminoma in an 86-Year-Old Shows Similar Proliferation Rate as in Younger Men

We present a rare case of classic seminoma in an 86-year-old man. Combined mitotic count, the presence or absence of intravascular invasion, and the expression of PCNA, Ki67, and p53 were compared between this octogenarian and the tumors of four randomly selected standard younger men. These histologic features were chosen to compare the potential biologic activity of these tumors. The phenotype of classic seminomas in octogenarians seems to be the same as in younger men, and treatment paradigms should remain unchanged.

FACTORS OF PROGNOSIS OF THE CANCER OF RECTUM II-III STADIUM AFTER PREOPERATIVE RADIATION THERAPY

We researched factors of prognosis of the cancer of rectum 2-3 stadium after preoperative radiation therapy. Correlative dependencies between apart prognostic rates which characterize complications of the main disease (development of recidives, production of metastasis) were estimated. Prognostic importance in quality of factors, negatively influencing on the prognosis of the disease was revealed. Tumor size, kind of growth and invasive growth into intestinal wall, quantity of lymphatic nodes with metastasis, high level of Ki-67, p53 expression, stage of malignancy, conditions of tumor edge and intravascular invasion occurred to be the most important. The results, we got, can be used in evaluation of the stage of risk of postoperative complications development after carried preoperative radiation therapy.

Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells

Placenta growth factor (PlGF; formerly PGF), a vascular endothelial growth factor gene family member, is expressed in human implantation sites by maternal uterine NK (uNK) and fetal trophoblast cells. Lower than normal concentrations of blood and urinary PlGF have been associated with impending onset of pre-eclampsia, a hypertensive disease of late human gestation characterized by limited intravascular trophoblast invasion. In pregnant rodents, delivery of the PlGF antagonist sFlt-1 or S-endoglin induces pre-eclampsia-like lesions. Mice genetically deleted in PlGF reproduce, but neither their implantation sites nor their uNK cell development are described. We combined real-time PCR of endometrium from nonpregnant and gestation day (gd)6-18 C57BL6/J (B6) mice with immunohistology to analyze PlGF expression in normal mouse pregnancy. To estimate the significance of uNK cell-derived PlGF, PlGF message was quantified in mesometrial decidua from pregnant alymphoid Rag2 null/common gamma chain null mice and in laser capture-microdissected B6 uNK cells. Histopathologic consequences from PlGF deletion were also characterized in the implantation sites from PlGF null mice. In B6, decidual PlGF expression rose between gd8-16. uNK cells were among several types of cells transcribing PlGF in decidualized endometrium. Immature uNK cells, defined by their low numbers of cytoplasmic granules, were the uNK cells displaying the greatest number of transcripts. PlGF deletion promoted the early differentiation high numbers of binucleate uNK cells (gd8) but had no other significant, morphometrically detectable impact on implantation sites. Thus, in mice, PlGF plays an important role in successful uNK cell proliferation and/or differentiation.

“Silent” Tyrosinemia Presenting as Hepatocellular Carcinoma in a 10‐year‐old Girl

“Silent” Tyrosinemia Presenting as Hepatocellular Carcinoma in a 10‐year‐old Girl

Canine Hemophagocytic Histiocytic Sarcoma: A Proliferative Disorder of CD11d+ Macrophages

Histiocytic disorders of dogs include histiocytoma, localized histiocytic sarcoma (HS), disseminated HS (malignant histocytosis), and the reactive histiocytoses: cutaneous and systemic. A common element to these diseases is proliferation of dendritic cells (DC) of either Langerhans cell (epithelial DC) or interstitial DC lineage. In this report, 17 dogs with hemophagocytic HS are described. Breeds affected included Bernese Mountain Dog (6), Golden Retriever (4), Rottweiler (3), Labrador Retriever (2), a mixed-breed dog, and a Schnauzer, which were from 2.5 to 13 years old. The dogs presented with Coombs negative responsive anemia in 16/17 dogs (94%), thrombocytopenia in 15/17 dogs (88%), hypoalbuminemia in 16/17 dogs (94%), and hypocholesterolemia in 11/16 dogs (69%). All dogs died or were euthanized. The clinical course ranged from 2 to 32 weeks (mean 7.1 weeks). Diffuse splenomegaly with ill-defined masses was consistently present. Microscopic lesions were prevalent in spleen, liver, lung, and bone marrow. Metastasis occurred by insidious intravascular invasion with minimal mass formation. Histiocytes were markedly erythrophagocytic and accompanied by foci of extramedullary hemopoiesis. Cytologically, the histiocytes varied from well differentiated to atypical, with atypia more prevalent in spleen than bone marrow. These tumors arose from splenic red pulp and bone marrow macrophages, which expressed major histocompatibility complex class II and the beta2 integrin, CD11d. They had low and/or inconsistent expression of CD1 and CD11c, which are dominantly expressed by canine nonhemophagocytic HS of DC origin. Canine histiocytic proliferative diseases now encompass proliferation of all members of the myeloid histiocytic lineage: Langerhans cells, interstitial DC, and macrophages.

Cavoatrial Tumor Extension in Children With Wilms Tumor

The aim of this study was to evaluate the clinical characteristics and treatment results of 17 children with cavoatrial tumor extension of Wilms tumor. Of the 360 Wilms tumors diagnosed between 1980 and 2000, 17 patients with intracaval thrombus were identified from the medical records at the pediatric oncology department of Hacettepe University. The following data were collected and reviewed: age, sex, presenting symptoms, tumor site, presence of anaplasia, stage, associated congenital anomalies, localization of tumor thrombus, radiologic findings, type and duration of preoperative chemotherapy, response to preoperative chemotherapy, recurrences, and survival. The frequency of cavoatrial extension in this group was 4.7% (15 in the inferior vena cava and 2 in the right atrium). Fourteen patients received preoperative chemotherapy consisting of two-drug regimen (vincristine and actinomycin D) ranging from 1 to 12 weeks (median 4 weeks). Since intravascular invasion is often asymptomatic, a careful radiologic examination to detect tumor thrombus before surgery is essential. There is no need for aggressive surgery in the presence of tumor thrombus. It may be resolved by preoperative chemotherapy. Surgical removal of the thrombus should be considered in the presence of life-threatening tumor thrombosis at diagnosis and in patients who had residual thrombus after chemotherapy.

METASTATIC LEIOMYOMATOSIS CAUSING SEVERE LOWER GIBLEED

A 41 year-old woman presented with tachycardia and black, tarry stools. Her past medical history included a diagnosis of “lung fibroids,” myomectomies for large uterine fibroids, and ultimately TAH/BSO. Three weeks after TAH/BSO she had a second operation for hemorrhage into a pelvic mass. The patient was then placed on conjugated estrogen. In March 2003 she required transfusion for hemoglobin (Hgb) of 4. 1g/dl. In June, palpitations awakened her. Blood tests revealed Hgb of 5.31g/dl. Patient was transfused 2 units PRBCs and sent home. Two days later, she again awoke tachycardic and was hospitalized. The patient was pale, but in no acute distress. Temperature was 36.1°C, RR 18, BP 115/60, P 100 without orthostasis. She had no rashes, petechiae or scleral icterus. There was a normal S1 S2, without murmur. Bowel sounds were normoreactive. Abdomen was nondistended, soft, nontender, without palpable masses. Rectal exam revealed guaiac positive black stool. White count was 5.3 k/mm3, Hgb and Hct were 8.1 g/dl and 26.0%, respectively, with MCV of 93.5 fl and RDW of 17.5%. Platelets were 243,000 g/mm3. PT/PTT/INR were normal. An upper and lower endoscopy; small bowel series; three bleeding scans; and a capsule endoscopy study were inconclusive. A chest/abdomen/pelvis CT revealed multiple soft tissue masses within the pelvis, one abutting the sigmoid junction and one abutting the upper rectum; multiple pulmonary nodules increased in size from prior CT in 1998; and a leiomyoma of the inferior vena cava (IVC) without invasion of the right atrium. Tissue from the TAH/BSO was retrospectively tested for estrogen (ER) and progesterone (PR) receptors with positive results. Gastrointestinal bleeding progressed to hematochezia. The patient required 22 units of PRBC's. Exploratory laparotomy revealed soft tissue masses entangling and invading both the ileum and the sigmoid colon. Pathology showed multiple benign hemorrhagic degenerating leiomyomata with vascular invasion. Leiomyomatosis is a rare, histologically benign smooth muscle tumor with a tendency to intravascular invasion. It is infrequently associated with life-threatening symptoms. What is unique to our case is the impressive intravascular invasion of the lower GI tract, which has never been reported in the literature, and which resulted in near-exsanguination. The ER/PR positivity of the tissue supports our hypothesis that estrogen therapy resulted in metastatic leiomyomatosis and the rapid invasion of multiple sites including the peritoneum, IVC, lungs, and GI tract.

Síndrome de vena cava superior y carcinoma insular de tiroides: el stent como alternativa terapéutica paliativa

The superior vena cava syndrome (SVCS) is a uncommon complication of thyroid cancers. It is produced as consequence of the mediastinal spread of the tumor or by intravascular invasion with thrombosis. We describe a case of insular thyroid carcinoma with an SVCS solved by putting an intravenous stent. The patient was a 73 year old male that consulted for aphonia and presence of a tumor in the right side of the neck of two months of evolution. The PAAF of thyroid suggested the diagnosis of "follicular tumor". A total thyroidectomy was performed on the patient and the sample histological study revealed the existence of a insular carcinoma. An ablative dosis of 131I was administered to him. One year after the patient developed the SVCS. A TAC detected a tumoral relapse consistent with clinical syntoms, and was confirmed by a high level of Tg (with TgAntibodies -). As the patient showed a slight response to radiotherapy (52Gy), a thoracic phlebography was realized demostrating an extense upper vena cava obstruction. After having accomplished an angioplasty, a long stent (20 mm wide) was put into the upper vena cava that was followed by a fast clinical and radiological improvement. A new phlebography practiced three month later showed a rapid venous flux through the stent, and near total disapperance of collateral circulation on thorax wall and mediastinum.

Cricoid Area of the Larynx: Its Physiological and Pathological Significance

The three-dimensional distribution of the cricoid area was investigated using computer graphics and its histological structure and pathology were studied using whole-organ serial sections. A total of 26 adult human larynges were examined. The findings were as follows: 1. Cricoid areas were located along the superior portion of the cricoid arch on both sides. 2. The cricoid area was surrounded by the perichondrium of the cricoid cartilage, the conus elasticus and the fibrous layer of the subglottic mucosa. 3. The cricoid area was a loose areolar area, mainly composed of adipose tissue and loose elastic and collagenous fibers. 4. Many vessels were present in the cricoid area and a superficial branch of the cricothyroid artery ran through it. 5. Vessels in the cricoid area penetrated the anteroinferior portion of the conus elasticus and extended into the prelaryngeal region. 6. In larynges with laryngeal carcinoma, cancer invasion into the cricoid area and intravascular tumor invasion facilitated metastasis to the prelaryngeal, pretracheal and/or paratracheal regions and stomal recurrence. Cricoid areas were related to the growth pattern of laryngeal cancer.

Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer

Background & Aims: Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined. Methods: The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice. Results: INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria. Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor α. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (≤8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P ≤ 0.05). Conclusions: These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer. GASTROENTEROLOGY 2000;118:36-47

舌癌Ｔ１・Ｔ２症例の再発因子 臨床病理学的検討

Significant factors related to primary recurrence of T1/T2 carcinoma of the tongue and neck lymph node metastasis were analyzed with the use of logistic analysis in 108 patients. All patients had undergone Cot laser resection between March 1980 and April 1997. The factors analyzed included: (1) primary site of the carcinoma, (2) differentiation of squamous cell carcinomas, (3) diameter of the primary tumor, (4) absence/presence of perineural invasion of the primary tumor, (5) absence/presence of intravascular invasion of the primary tumor, (6) absence/presence of in-tramuscular invasion of the primary tumor, (7) depth of primary tumor invasion. (8) surgical margin of the resected primary tumor, and (9) absence/presence of irradiation. Significant risk factors for primary recurrence were a surgical margin of less than 4 mm and tumor coverage of the posterior third of the mobile tongue. A significant risk factor in neck lymph node metastasis was depth of primary tumor invasion of more than 4 mm, no other significant factors for the primary recurrence or regional recurrence were observed. The results suggested that a deep surgical margin of more than 10 mm was nesessary, and that if the primary lesion occupied the posterior third of the mobile tongue, an extended surgical resection was nesessary. In addition, if the depth of the primary tumor invasion is more than 4 mm, preventive modified radical neck dissection is recommended.

Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer

BACKGROUND: C-reactive protein (CRP) is a product synthesized in hepatocytes and has been reported to be upregulated by such proinflammatory cytokines as interleukin-1, interleukin-6, and tumor necrosis factor. The significance of a preoperative serum elevation in CRP as a predictive indicator for the malignant potential and prognosis in colorectal cancer has not been elucidated. METHOD: One hundred and twenty consecutive patients with colorectal cancer, whose local lesions were resected in our department, were selected. Any patients with inflammatory diseases such as infection or collagen diseases were excluded from the current study. The preoperative serum CRP level was measured, and the relationship between the serum elevation of CRP and both the clinicopathologic factors and prognosis of the patients was investigated. RESULTS: The incidences of liver metastases, peritonitis carcinomatosa, histopathologic lymph nodes metastasis, and intravascular invasion in patients with a preoperatively elevated serum CRP level were significantly more frequent than in those with a negative serum protein level. The survival rates of the patients without a preoperative elevation of the serum CRP proved to be significantly more favorable than that of the patients with such an elevation ( P<0.001). CONCLUSIONS: A preoperative serum elevation of CRP was thus found to be an indicator of the malignant potential of the tumor as well as a predictor of the prognosis of patients with colorectal cancer.

Keratoacanthoma

Keratoacanthomas are distinct skin lesions that occur most often as solitary tumors in sun-exposed areas in elderly, fair-skinned patients. Clinically, these tumors are characterized by a rapid onset and regression within months. Keratoacanthomas display distinct histological features including a keratin-filled crater lined by a proliferating squamous epithelium. Cytologically, there may be overlap with classical well differentiated squamous cell carcinoma. Rarely, otherwise typical keratoacanthomas show intravascular and perineural invasion and lymph node metastases. Keratoacanthomas should, therefore, be considered to be a clinically distinct variant of well differentiated squamous cell carcinoma capable of spontaneous regression. This view is supported by their common etiology, occasional concurrent occurrence, and a multitude of studies revealing no substantial differences between these two lesions. Regression is immunologically mediated and activated by a variety of molecular mechanisms. Considering the common nature of keratoacanthomas and well differentiated squamous cell carcinomas, and the lack of any features predicting prognosis, surgical excision of keratoacanthoma is advisable.

Cell adhesion molecules: their role in pregnancy

The adhesion of cells to each other, to other cell types and to the extracellular matrix (ECM) is a crucial part of development and relies on the expression of cell adhesion molecules (CAMs) and their ligands. For example, at implantation, the trophoectoderm attaches to the uterine epithelial surface and CAMs play a major role in this process. Following attachment, interstitial and intravascular invasion of maternal tissue by trophoblast is required to develop the maternal-placental-fetal circulation and this too requires a new repertoire of CAM expression. Understanding the part played by adhesion molecules in pregnancy is paramount because several pregnancy associated disorders including pre-eclampsia, fetal growth retardation, miscarriage and infertility problems have been linked to abnormalities in expression of particular CAMs and/or their ligands. The aim of this article is to review the major CAM families and their role in human pregnancy. Excellent reviews which include reference to animal studies can be found elsewhere.

Pulmonary Tumour Embolism Complicating a Case of Leiomyosarcoma

Patient. A case of peripheral leiomyosarcoma presenting with features of pulmonary thromboembolism is described. Discussion. Persistence of the embolus despite triple-armed thrombolytic therapy and the presence of intravascular tumour invasion suggest the rare entity of pulmonary tumour embolism from a leiomyosarcoma.

Prognosis following locally recurrent soft‐tissue sarcoma. A staging system based on primary and recurrent tumour characteristics

We have shown that the clinical growth rate of local recurrence from soft-tissue sarcoma could be expressed as a growth-rate index (GRI) which was predictive for metastasis, and which was able to identify 2 equal populations of good (80% 2-year MFS) and poor survivors (33%). We now report the associations between characteristics of the primary and GRI, and combine primary and locally recurrent tumour characteristics in a staging system. We studied 460 adult patients with soft-tissue sarcomas of the extremities and trunk wall who were diagnosed and treated between 1964 and 1990, of whom 134 developed local recurrences and 151 metastases. The association of primary tumour size, histologic malignancy grade, depth, spontaneous necrosis, intratumoral vascular invasion and S-phase fraction with local recurrence, GRI and metastasis were examined. High GRI was associated with primary tumours that were larger, deeper, more malignant, underwent spontaneous tumour necrosis, demonstrated intravascular invasion and had a higher S-phase fraction. The same factors were also strongly associated with the incidence of metastasis. A multivariate analysis found GRI and primary tumour necrosis to be the strongest and most significant prognostic factors. GRI and tumour necrosis were combined in a staging system that identified groups with good survival (79 to 94% 2-year MFS), intermediate survival (61% 2-year MFS) and exceptionally poor survival (6% 2-year MFS). These findings validate our earlier assertion that high GRI reflects highly malignant tumours. A staging system composed of primary tumour necrosis and GRI can identify patients who may be suitable candidates for trials of adjuvant chemotherapy.

Prognostic value of Ki-67 expression in 182 soft tissue sarcomas. Proliferation--a marker of metastasis?

Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki-67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki-67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty-two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow-up time for survivors was 6 years (1-13). We used a semiquantitative score to the assess percentage of Ki-67-positive cells: < or = 10% (n = 86), > 10-25% (n = 57), > 25-50% (n = 30), > 50-75% (n = 7), > 75-100% (n = 2). Increasing Ki-67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S-phase fraction, and metastasis. A Ki-67 index Ki-D < or = 10% (n = 86) and > 10% (n = 96) defined two groups who had 84% and 56% 3-year metastasis-free survival (p = 0.0001), respectively. Tumours with Ki-D > 10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S-phase fraction. Ki-67 expression may be helpful in predicting survival of patients with soft tissue sarcomas.

喉頭原発の転移性甲状腺癌

A rare case of metastasis of laryngeal carcinoma to the thyroid gland is reported. The patient was a 61-year-old male who had received laser surgery followed by radiotherapy for laryngeal carcinoma 29 months earlier. He complained of hoarseness since June 18, 1991. Thyroid tumor of the left lobe and ipsilateral recurrent laryngeal nerve palsy were observed. No cervical lymphnode swelling was palpated. On CT scan, tumor was detected in the left thyroid lobe. Hemithyroidectomy and paratracheal lymphnode dissection were performed on July 22. Histological examination revealed the same histological type as the previous laryngeal carcinoma, moderately differentiated squamous cell carcinoma, and intravascular invasion. Total thyroidectomy and left modified neck dissection followed by radiotherapy (30Gy) were performed. The patient has lived, without any evidence of disease, for 11 months after treatment.

The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: A matched case-control study

Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case-control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas.

Age as a prognostic factor in patients with squamous cell carcinoma of the uterine cervix

Correlations between age and several prognostic factors, such as histologic cell type, depth of invasion, intravascular invasion, and lymph node metastases (LNM), were analyzed in squamous cell carcinoma of the cervix (SCC). A total of 380 patients with Stage IB or more advanced SCC underwent radical hysterectomy at the authors' institution from 1971 to 1987. The cases were divided into four age groups: 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 69 years. The depth of invasion was classified in four categories according to pathologic examination of surgical specimens. The only significant factor was the frequency of LNM with deeper invasion, which was less in the 60-to-69-year age group than in the younger age groups. The 5-year survival rates of the patients with LNM also were higher in the 60-to-69-year group. Thus, age 60 or older can be considered a prognostic factor correlating to LNM in squamous cell carcinoma of the cervix.