Ultrastructure of capillary permeability in human brain tumor: disseminated and metastatic medulloblastoma

The ultrastructure of the tumor vessels of primary cerebellar, subarachnoidal disseminated and extraneural metastatic medulloblastomas was studied. They were compared with those in glial, nonglial and metastatic brain tumors which have been previously reported. Twelve surgical specimens were examined. Seven tumors were limited to the vermis, the floor of the fourth ventricle and the cerebellar hemispheres. Four gross nodule seedings were demonstrated in the cerebral and spinal subarachnoid space. One metastasis was demonstrated in the subclavicular lymph node. Ultrathin section of those tumors and replica specimens were studied under the transmission electron microscope. The tumor vessels of primary medulloblastoma and glial tumors had nonfenestrated capillaries and were morphologically similar to normal brain capillaries. On the other hand, the tumor vessels of disseminated and metastatic medulloblastoma, nonglial tumors, and metastatic brain tumors had fenestrated capillaries. These findings were anticipated because the arachnoid membrane and lymph nodes have fenestrated capillaries. The presence of fenestration suggests that the tumor vessels of disseminated and metastatic brain tumors resemble the blood vessels found in normal arachnoid membrane and lymph nodes.     

Ultrastructure of capillary permeability in malignant lymphoma

The ultrastructure of the blood vessels of primary central nervous system malignant lymphoma was studied and compared with those in glial, non-glial and metastatic brain tumors. Five surgical specimens were studied by conventional ultrathin section and freeze-fracture replica techniques. Tumor vessels of various sizes were found. The luminal surfaces of the tumor vessels were irregular and the basal lamina had multiple-layer structure. The perivascular spaces were enlarged and infiltrated with tumor cells. The endothelium had marked infoldings, increased pinocytotic vesicles and fenestrations. The intercellular junctions were short but no obvious opening was seen. On the replica specimen pinocytotic vesicles were calculated on an average of 28 per microns2. The essential features of the blood vessels in primary central nervous system malignant lymphoma were the fenestrated vessels. They resembled the blood vessels found in non-glial and metastatic brain tumors, but were distinctly different from those seen in glial tumors with non-fenestrated vessels.     

Ultrastructure of capillary permeability in human brain tumors--4: Cerebral edema associated with meningiomas

The cerebral edema, as judged by computed tomographic scan, associated with supratentorial meningiomas was assessed in 43 cases. No relationship to the occurrence or the degree of edema could be established with respect to meningioma location and histological type. The larger the meningioma, the more likely the presence of and the severity of cerebral edema. The materials were obtained from surgically removed specimens in 6 cases of meningiomas with and without associated cerebral edema, and tumor vessels were studied with conventional ultrathin section and freeze-fracture replica techniques. The characteristic findings of these tumor vessels were thinning of endothelium and many fenestrations, short and in fact open tight junctions. Tight junctions between endothelial cells were composed of one or two strands which appeared to be a discontinuous array of particles. The ultrastructural appearance of tumor vessels is similar to that seen in meningiomas with and without associated cerebral edema.     

Ultrastructure of capillary permeability in human brain tumors. Part 1: Gliomas associated with cerebral edema (low density area)

In order to elucidate pathogenesis of perifocal edema in the human brain tumors, we observed the alteration of capillary permeability between the glioblastomas with remarkable edema (4 cases) and astrocytoma with slight edema (3 cases). Specimens were studied by conventional ultrathin section and freeze-fracture replica technique. In ultrathin sections of capillaries in glioblastomas, some of these cell junctions were tortuous, elongated, in fact, open. Other capillary abnormalities included endothelial hyperplasia with extensive vesicular formation, surface infolding of endothelial cells, irregularity of the basal lamina and the presence of a large collagen filled extracellular space. In freeze-fracture replicas of capillary endothelium, pinocytotic vesicles markedly increased and were an average fo 52 per micron. Tight junction in one area was seen as network of 6 strands composed of about 100A particles, but in the other areas as one or two strands. In ultrathin sections of astrocytoma, yet there were blood vessels appeared relatively normal. In freeze-fracture replicas, pinocytotic vesicles markedly increased and were an average of 34 per micron. Tight junction was seen as network of 7 strands. We concluded that fewer strands of the tight junction play an important role in increasing the permeability in the vessels of glioblastomas with severe perifocal edema, in addition to increasing the pinocytotic vesicles.     

腰段原发性脑脊膜黑色素细胞瘤1例

1　病例资料患者 ,男 ,5 5岁 ,在无明显诱因下出现腰痛、双下肢抽搐、疼痛伴尿潴留 2个月 ,且进行性加重。入院前 1周出现行走困难。查体 :脊柱外观无畸形 ,腰段有压痛 ,双下肢肌力为Ⅳ级 ,会阴部、小腿内侧面及足背内外侧面感觉丧失。肌电图 :双侧胫前肌群和腓肠肌失神经元性改变。脊髓造影 :造影剂在Ｌ2 运行受阻 ,呈杯口状改变。手术所见 :Ｌ2 硬膜膨胀 ,饱满 ,无搏动 ,硬膜与珠网膜粘连。Ｌ1,2 处的马尾神经正中有上下带蒂的葫芦形包块 ,约 2ｃｍ× 2ｃｍ× 1 5ｃｍ ,与马尾神经粘连 ,包块有包膜 ,与周围神经界限清楚 ,褐色 ,呈菜花状 ,…     

Care for dying patients with primary malignant brain tumor

Patients with primary malignant brain tumor experience deterioration of multi-focal neurological deficits such as hemiparesis, aphasia, visual field defects, dysphagia, and disturbance of recent memory at the advanced stage of disease. With these advancing neurological deficits, many patients will inevitably prepare for death and may experience psychological and spiritual distress. Active listening is an important skill to explore the fears of patients with a terminal illness but in the advanced stage of a primary brain tumor, patients usually have great difficulty with verbal expression. Even if patients do not suffer from complete expressive aphasia, they often have difficulty verbalizing their thoughts and feelings. Sadly, disturbance of vocal expression is a common accompaniment of this pathology. Unless the pathophysiology is understood, an observer may fail to comprehend the patient's non-verbal communication. Seeking to understand these issues is a prerequisite of the preservation of dignity and provision of ethical care for such patients.     

Desmoplastic malignant melanoma: An aggressive tumor

Summary The clinical features and histological appearance of desmoplastic malignant melanoma are presented. Aggressive surgical management and close follow-up are mandatory if this highly aggressive tumor is to be controlled. Despite this, the prognosis is poor.     

Metastatic malignant melanoma of unknown primary site to the brain: A case report

Introduction and importanceThe natural history of metastatic melanoma in the absence of a known primary site has been poorly defined. The disease usually presents a significant cause of morbidity and mortality. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. The disease is frequently diagnosed after treatment for known extracranial metastases and has a poor outcome despite various local and systemic therapeutic approaches.Case presentationHerein, we present a case of a 43-year old female presented with history of headaches and enlarged a left inguinal lymph node. Notably, no cutaneous lesions could be identified by history or on physical examination. CT-scan of the brain revealed a space occupying lesion and the inguinal lymph node biopsy confirmed the diagnosis of metastatic malignant melanoma. The patient succumbed shortly after establishment of diagnosis.Clinical discussionMost patients with brain metastases from malignant melanoma are diagnosed after treatment for known extracranial metastases and have a poor outcome despite various local and systemic therapeutic approaches.ConclusionMetastatic melanomas of brain with unknown primary present a significant morbidity and mortality and confer a poor prognosis. Delay in diagnosis and treatment is of serious concern when it comes to improve the prognosis of patients with this disease. The optimal treatment depends on the objective situation, often surgery, radiosurgery, whole brain radiotherapy and chemotherapy can be used in combination to obtain longer remissions and optimal symptom relieve.     

Ultrastructural study of capillary permeability of liposome-encapsulated cisplatin in an experimental rat brain tumor model

The anticancer chemotherapeutic agent cisplatin (cis-diamminedichloroplatinum) has several disadvantages, including extreme nephrotoxicity, rapid binding to plasma proteins, and poor penetration into the central nervous system. Liposomes would seem to be suitable as carriers of cisplatin to brain tumors. This ultrastructural study was undertaken to identify the capillary permeability of liposome-encapsulated cisplatin in a rat brain tumor model. Brain tumors were induced transplacentally with a single intravenous dose of 50 mg/kg of ethylnitrosourea (ENU). One ml of liposome-encapsulated cisplatin and ferritin prepared from phosphatidylcholine and cholesterol (molar ratio 7:2) was administered via the carotid artery to rats with ENU-induced brain tumors. The tumor platinum content and that of the contralateral hemisphere were assayed by flameless atomic absorption spectrometry. The presence of ferritin-bearing liposomes was demonstrated by electron microscopy of brain capillary endothelium as well as tumor cells. Thirty minutes after drug administration, the average dry-weight platinum concentrations were 3.98 +/- 0.50 micrograms/g within the intracerebral tumors and 0.72 +/- 0.24 micrograms/g in the contralateral hemispheres. Electron microscopic ultrastructural study, which can distinguish ferritin-bearing liposomes from cell materials, demonstrated the presence of liposomes containing ferritin in both cell surface folds and capillary endothelial cells and also within tumor cells. An enlarged electron micrograph of a liposome with a diameter of approximately 0.2 micron suggested the presence of ferritin molecules in the lamellar structure. Liposome-encapsulated cisplatin is apparently able to pass the blood-brain barrier and should be useful in the chemotherapy of glioma.     

Transition from meningeal melanocytoma to primary cerebral melanoma. Case report

The authors describe the first case of an intracranial transition of a melanocytoma into a primary malignant melanoma within a short time. A 37-year-old woman presented with progressive brainstem syndrome due to a tumor, originally diagnosed and treated 12 years earlier, that extended from the petroclival area to the anterior craniocervical junction. The histological workup following subtotal tumor resection of the initial tumor had revealed the typical features of a fibrous melanocytic meningioma without increased proliferation. Ten years after the patient had completed treatment for the melanocytic meningioma, control neuroimaging demonstrated growth of the residual tumor with compression of the brainstem. Another neurosurgical intervention revealed a dark tumor of hard consistency. At this time immunohistochemical examinations demonstrated melanocytic features (expression of vimentin, S100 protein, and melan A) of the lesion with focally increased proliferation (5% of Ki-67-positive cells) but no higher mitotic activity. Clinical signs of deterioration along with imaging-confirmed tumor progression precipitated another operation within 7 months. A neuropathological examination revealed epithelial and anaplastic changes and indicated that the MIB-1 indices were greater than 25%. Pleomorphic changes and a focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma. The patient's later clinical course consisted of a rapid diffuse meningeal spread of the lesion throughout the entire brain and spine. Despite whole-brain and stereotactic radiation therapy as well as chemotherapy, the patient died 4 months after the last neuropathological diagnosis. Although grossly resembling a meningioma, melanocytomas lack the former's histological and immunohistochemical features. The biological behavior of a melanocytoma is variable and recurrence may happen after subtotal resection, but intracranial transition into a malignant melanoma has not been observed previously.     

Extensive primary malignant melanoma of the oesophagus

Primary malignant melanoma of the oesophagus (PMME) is a rare tumour. It has characteristic pathological and immunohistochemical features and diagnosis and management is difficult. This paper reports a patient with PMME, with a review of literature. The literature search was made with the Index Medicus/MEDLINE database using ‘melanoma’ and ‘oesophagus’ as key words, and cross‐referencing of other articles on the subject. Three‐phase oesophagectomy was performed and the patient died 2 months afterwards with respiratory failure and bone metastasis. Primary malignant melanoma of the oesophagus is a highly lethal tumour. Radical surgery is the treatment of choice.      

Rare primary malignant melanoma of the lung

Primary malignant melanoma of the lung is a very rare but very aggressive tumour. We report two patients who had primary malignant melanoma of the lung and underwent surgical resection in our hospital. Both of them had lymph node metastases and received postoperative adjuvant therapy. They died of tumour recurrence in 12 and 37 months. Management of this uncommon tumour is difficult and has not been standardized, but surgical resection is the only treatment option.     

Plantar lentiginous melanoma: a distinctive variant of human cutaneous malignant melanoma

The neoplastic system of human cutaneous melanoma includes three generaly recognized variants: lentigo maligna, superficial spreading melanoma, and nodular melanoma. Lentiginous melanomas other than lentigo maligna constitute a fourth group, of which plantar lentiginous melanoma qualifies as an anatomic subgroup. Histologically and clinically, plantar lentiginous melanoma (PLM) is characterized by a period of radial growth and often by one or more foci of regression. In 27 of 33 plantar melanomas, a characteristic lentiginous, radial component of melanocytic proliferation was noted. In the remaining six cases, histological material failed to document a radial component. Eighteen of the 27 patients with PLM were blacks, and 18 patients died of distant metastasis. Tumors invasive to level II did not metastasize, but at levels IV and V and in tumors with a high mitotic rate, the prognosis was poor. The presence of lymph node metastases at the time of initial therapy correlated with a poor prognosis group.     

阴茎原发恶性黑色素瘤4例

目的 探讨阴茎原发恶性黑色素瘤的临床症状、病理特点及诊断治疗.方法 对4例阴茎原发恶性黑色素瘤的病理和临床资料进行回顾性分析.结果 4例均行阴茎部分切除,双侧腹股沟淋巴结清扫术.术后4例均行化疗,其中2例化疗联合生物学治疗.结论 阴茎原发恶性黑色素瘤临床罕见,确诊依靠病理,手术为主要治疗手段,术后行化疗联合生物学治疗可提高生存期,但因其恶性程度高,预后不佳.     

Metastatic malignant melanoma resembling malignant peripheral nerve sheath tumor: report of 16 cases

We report 16 cases of metastatic malignant melanoma presenting clinically as lymphadenopathy or a soft-tissue mass and histologically resembling malignant peripheral nerve sheath tumor (MPNST). In two cases, the metastatic malignant melanoma was preceded by a primary cutaneous malignant melanoma; in four cases, it presented synchronously with such a tumor; and in 10 cases, there was no evidence of a previous or concomitant malignant skin lesion. Histologically, the tumors were characterized by a malignant-appearing spindle cell proliferation arranged in fascicles, often accompanied by a peritheliomatous growth pattern, alternating hypercellular and hypocellular areas, numerous mitoses, and foci of necrosis. In nine cases, there was residual lymph node tissue. In none of the cases was there evidence of an anatomic connection with a nerve, a coexistent neurofibroma, or the stigmata of neurofibromatosis. Fourteen of the cases showed strong and generally diffuse immunoreactivity for S-100 protein, and five cases showed positivity for HMB-45. Four of eight patients with follow-up information died of the disease. Tumors with a microscopic appearance compatible with MPNST but showing strong diffuse S-100 protein staining and featuring remnants of lymph node may represent metastatic malignant melanomas and should elicit a search for a previous or concomitant tumor in the skin and other sites. The similarities these tumors share with MPNST are probably related to their common neuroectodermal histogenesis.     

Recommended width of excision for primary malignant melanoma

Wide local excision for melanoma with margins of 3 to 5 cm have been advocated in the literature for nearly 140 years. These reports have grouped all stages of melanoma rather than addressing primary early stage disease. Breslow first advocated limited excision margins for these tumors. We have been excising all thicknesses of melanoma with a limited margin (1.00–1.50 cm, mostly 1.00 cm) since 1975. We advocate a 1 cm excision margin irrespective of tumor thickness. Clark has shown that melanoma invades in a vertical fashion, and thus one would expect to be more generous in depth than in width on a pathologic basis. Two studies have shown that there is no difference in the increase in locoregional recurrence and no change in death rate from the disease with more conservative treatment margins. Excision of this lesion is not an office procedure. It should be performed meticulously in an operating room, preferably under light general anesthesia.

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Resumen La resección amplia de un melanoma con márgenes de 3 a 5cm, ha sido preconizada en la literature por cerca de 140 años. Los informes publicados agrupan pacientes en todos los estadíos, y no realmente la enfermedad en su estado precoz. Breslow fue quien primero publicó buenos resultados de la resección con márgenes limitados. Nuestro grupo ha venido resencando los melanomas de todos los espesores con un margen limitado (1.00 a 1.50 cm, más frecuentemente 1.0 cm) desde 1975. Nuestra política es un margen de resección de 1cm, no importa cual sea el espesor del tumor. Clark ha demonstrado que el melanoma se extiende de manera vertical y que, por consiguiente, desde el punto de vista histopatológico uno debe ser generoso en lo referente a profundidad más que a extensió. Dos estudios han demostrado que no existe diferencìa en cuanto a recurrencia localregional y que tampoco varían las tasas de mortalidad cuando se emplean márgenes más conservadores. Le resección del melanoma no es un procedimiento de consultorio, sino una operación para ser realizada en forma meticulosa en un quirófano, de preferencia bajo anestesia general.

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Résumé On a préconisé des résections larges avec des marges entre trois et cinq centimètres depuis bientôt 140 ans. Ces rapports concernaient tous les stades confondus et n'intéressaient pas les stades précoces. Breslow le premier a rapporté de bons résultats avec des résections limitées de ces mêmes tumeurs. Nous résequons les mélanomes quelle que soit leur épaisseur, avec une marge de sécurité de 1.0 à 1.5 cm (plutôt 1.0) depuis 1975. Nous recommandons une résection avec une marge de sécurité de 1.0 cm quelle que soit son épaisseur. Clark a démontré que le mélanome envahit verticalement, argument qui à priori serait en faveur d'une excision en profondeur plutôt qu'en largeur au plan anatomopathologique. Deux études ont montré qu'il n'y avait aucune différence de récidive locorégionale ou de mortalité en cas de résection avec marges limitées. Ce n'est pas pour autant une intervention qui se fait en cabinet, mais qui doit se pratiquer méticuleusement en salle d'opération sous anesthésie légère.

     

Renal metastasis of malignant melanoma with unknown primary

The kidney is a common location for micrometastases in patients with malignant melanomas. These lesions are usually small, multiple, asymptomatic, and bilateral, and associated with a known primary lesion. This is an unusual case of a 38-year-old woman, with no history of melanoma, presenting with an asymptomatic solitary renal mass and two lung masses. She was doing well 3 months after laparoscopic radical nephrectomy and one course of interleukin-2 therapy.