Assessment of cosmetic outcome of oncoplastic breast conservation surgery in women with early breast cancer: a prospective cohort study.

BACKGROUND: The aim of this study was to assess the cosmetic outcome of patients undergoing oncoplastic breast conserving surgery in Indian population. MATERIALS AND METHODS: A prospective cohort of 35 patients who were eligible for breast conservation surgery was included in the study from year 2007 to 2009. Patients with central quadrant tumors were excluded from the study. A double - blind cosmetic assessment was done by a plastic surgeon and a senior nurse not involved in the management of patients. Moreover, self-assessment was carried out by the patient regarding the satisfaction of surgery, comfort with brasserie, social and sexual life after oncoplastic surgery. RESULTS: In this study, 35 patients underwent oncoplastic breast conservation surgery by various techniques. The cosmetic outcome scores of the surgeon and nurse were analyzed for inter rater agreement using inter-class Correlation Coefficients. There was a good association between them. The risk factors for poor cosmetic outcome was studied by univariate analysis and significant correlation was obtained with age, volume of breast tissue excised and estimated percentage of breast volume excised (P < 0.05). Moreover, 96% of patients were moderately to extremely satisfied with the surgery. Patients were offered an option for cosmetic correction of contralateral breast by mastopexy or reduction mammoplasty however, none of them agreed for another procedure. CONCLUSIONS: Oncoplastic breast surgery helps to resect larger volume of tissue with wider margins around the tumor. It helps to achieve better cosmesis and extends the indications for breast conservation. Most of the patients were satisfied with mere preservation of the breast mound rather than a symmetrical contralateral breast.

Scrofulous swelling of the bosom masquerading as cancer.

Tuberculosis of breast is very rare with an incidence of 0.1-0.5%. It can be primary or secondary. Except in patients presenting with sinuses, it is a challenge to diagnose it. A 40 year old premenopausal lady presented with breast lump increasing in size for 3 months. Mammogram showed a lesion suspicious of malignancy and trucut biopsy showed necrotic material only. Intraoperatively there was caseous necrosis and the tract from breast was extending to rib. It is a rare case with few case reports been reported where a rib tuberculosis presents as a breast lump rather than retromammary abscess.

Endovascular histologic effects of ultrathin gold- or vitronectin-coated platinum aneurysm coils in a rodent arterial occlusion model: a preliminary investigation.

BACKGROUND AND PURPOSE: Novel stratagems to improve the efficacy of platinum coils in occluding cerebral aneurysms have primarily involved coating coils with materials thought likely to provoke more desirable histologic reactions. No investigations to date, however, have evaluated the utility of gold or vitronectin coatings, despite known endovascular histologic effects of these agents, which may be favorable for treating cerebral aneurysms. This study was conducted to evaluate the degree of endovascular histologic change associated with ultrathin gold- or vitronectin-coated platinum coils. It was hypothesized that such coatings would increase intra-aneurysmal intimal hyperplasia and the degree of luminal occlusion compared with standard platinum coils. MATERIALS AND METHODS: The ligated carotid artery rat model was used to study 4 different aneurysm coil conditions: no coil (sham-surgery controls), uncoated platinum coil, and gold- or vitronectin-coated platinum coil. Two weeks postimplantation, the aneurysms were harvested and stained with hematoxylin-eosin. Slides were evaluated for the degree of neointimal response by a pathologist blinded to treatment. Additional quantitative evaluation was performed blindly by using the ratio of intimal-to-luminal cross-sectional area. RESULTS: A gold- or vitronectin-coated platinum aneurysm coil produced a statistically significant increase in neointimal response compared with a sham (no coil). Arterial segments treated with gold-coated platinum coils also demonstrated a statistically significant 100% increase in neointimal response compared with those treated with bare platinum coils. CONCLUSIONS: In concordance with our hypothesis, ultrathin coatings of gold provoked a neointimal response and degree of luminal occlusion greater than that of plain platinum aneurysm coils in a rat arterial occlusion model.

A morphologic study of the vasculature of malignant gliomas using thick celloidin sections and alkaline phosphatase stain.

The combination of 100 microm thick celloidin sections and alkaline phosphatase (AP) enzyme histochemistry of the vascular endothelium offers a greatly enhanced, 3D morphologic perspective and reveals intricate details of the vasculature of brain. A study of tumor specimens obtained at craniotomy from 6 patients with glioblastomas, 1 with anaplastic oligodendroglioma and 1 with juvenile pilocytic astrocytoma was undertaken using this technique. Five of the 6 glioblastomas, the anaplastic oligodendroglioma and the low-grade astrocytoma specimen showed uniform staining of afferent tumor blood vessels. In the glioblastomas, newly formed vessels formed dense, festooned networks at the advancing edges of the tumor. Feeding arteries entered the tumor at the junction between the edge of the tumor and adjacent brain or meninges and proceeded to form striking, coiled vessels and smaller branches. The density of both small arteries and veins was greatly increased within the tumor although there was much variability. Disordered arborization, arteriole to venous and arteriole to arteriole shunts were observed, leading to a situation where arteries connected directly to veins. In necrotic areas, there were often no AP-stained vessels. In many places, arterioles and capillaries were lacking. Numerous AP-negative veins of various sizes drained the tumors. Glomeruloid proliferations were presumptively identified as focal stain smudges or clusters of capillaries arising from nearby vascular channels. Increased alkaline phosphatase staining and/or focal new vessels were seen outside necrotic areas. The pilocytic astrocytoma and the oligodendroglioma showed less dense vascularity and no formation of the focal festoons of vessels shown by the glioblastomas. This technique may be useful for the study of tumor angiogenesis and to evaluate vascularity in experimental and human brain tumors after various therapies.

Spontaneously remitting dermatomyositis.

Dermatomyositis (DM) is an inflammatory myopathy of skeletal muscle with characteristic cutaneous findings. It is a rare disorder with a bimodal age distribution that affects almost twice as many women as men. One category of DM, normal-enzyme DM, is characterized by cutaneous changes only at baseline, normal serum muscle enzyme levels and myositis demonstrated by electromyography (EMG) and/or muscle biopsy specimens. Typically, patients with normal-enzyme DM progress to severe muscle involvement and require systemic corticosteroid therapy. The patient we report has normal-enzyme DM confirmed by serial serum enzymes, EMG, and skin and muscle biopsies but is unique in that she never experienced progression of muscle weakness although muscle involvement was documented histologically and by EMG. Follow-up examination after 1 year revealed near-complete resolution of cutaneous involvement after topical therapy and no evidence of muscle weakness.

A three-dimensional study of brain string vessels using celloidin sections stained with anti-collagen antibodies.

The purpose of this study was to explain the morphology and significance of string vessels in human brains. Brain slices (1.5 cm thick) were embedded in celloidin, sections cut at 100 microm and stained with antibody to collagen IV. A second component of the study was a 3-D rotational study for which we used sections stained with propidium iodide for cell nuclei and anti-collagen stain for blood vessel basement membranes. The materials consisted of brain from two infants at 28 and 35 weeks gestation, two term infants at 20 days and 3 months, one 5 years old, and 3 adults aged 25, 57, and 84 years. String vessels were counted in at least six fields of deep white matter using a 10x objective and the counts averaged and expressed as string vessels per cubic mm. The 3-D rotational study using confocal microscopy was designed to find nuclei in string vessels. The least number of string vessels were present in the premature infant. All others had comparably similar numbers of string vessels except the two term-born infants in whom there was a 3-5-fold increase. However, the two brains had other pathologic lesions, which could affect the counts. In normal brains, string vessels appear as a singe line of stain and usually connect two arterioles or capillaries. They can form loops and occasionally a string vessel may continue into a normal capillary. String vessels have rare nuclei. Our study indicates that string vessels are present in utero, increase in number and are present throughout life. Their exact nature remains unexplained. They apparently do not represent age-related acquired atrophy of capillaries because they are present at all ages and do not progressively increase with normal aging. This technique appears suitable for the study of large number of string vessels.

Cerebrovascular pathology in Alzheimer's disease and leukoaraiosis.

A high percentage of patients with Alzheimer's disease (AD) show evidence of white matter degeneration known as leukoaraiosis (LA), which is due to chronic ischemia. We found that the periventricular veins tend to become occluded by multiple layers of collagen in the vessel walls in the elderly. This collagen deposition is particularly excessive in LA lesions. Therefore, it is present in the brains of many AD patients, along with other ischemia-causing cerebrovascular pathology. We found evidence that there is severe loss of oligodendrocytes in LA, due to extensive apoptosis. No evidence of inflammation was found in the LA lesions. In thick celloidin sections of AD brain, we have obtained detailed 3D views of small (early) deposits of amyloid (stained with beta-amyloid antibody) around capillaries (stained with collagen IV antibody).

Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli.

BACKGROUND AND PURPOSE: Many patients who undergo cardiac surgery assisted with cardiopulmonary bypass (CPB) experience cerebral injury, and microemboli are thought to play a role. Because an increased duration of CPB is associated with an increased risk of subsequent cerebral dysfunction, we investigated whether cerebral microemboli were also more numerous with a longer duration of CPB. METHODS: Brain specimens were obtained from 36 patients who died within 3 weeks after CPB. Specimens were embedded in celloidin, sectioned 100 microm thick, and stained for endogenous alkaline phosphatase, which outlines arterioles and capillaries. In such preparations, emboli can be seen as swellings in the vessels. Cerebral microemboli were counted in equal areas and scored as small, medium, or large to estimate the embolic load (volume of emboli). RESULTS: With increasing survival time after CPB, the embolic load declined (P<0.0001). (Lipid emboli are known to pump slowly through the brain.) Also with increasing time after CPB, the percentage of large and medium emboli became lower (P=0.0034). This decline is consistent with the concept that the emboli break into smaller globules as they pass through the capillary network. A longer duration of CPB was associated with increased embolic load (P=0. 0026). For each 1-hour increase in the duration of CPB, the embolic load increased by 90.5%. CONCLUSIONS: Thousands of microemboli were found in the brains of patients soon after CPB, and an increasing duration of CPB was associated with an increasing embolic load.

Apoptosis in leukoaraiosis.

We report a case of leukoaraiosis that was studied for apoptosis. In the neuropil, the number of cells that showed DNA fragmentation was 2.5 times as great in the area of leukoaraiosis as in the adjacent white matter (P = .004) and 25 times as great as in the nearby cortex (P < .001). Our findings suggest that apoptosis, predominantly of oligodendrocytes, is involved in the pathogenesis of leukoaraiosis. Within the area of leukoaraiosis, we also found numerous small veins that were partially occluded by severe collagenous thickening of the vessel walls. This collagenosis may have contributed to or resulted from chronic ischemia in that area.

Multivariate analysis of laminar patterns of neurodegeneration in posterior cingulate cortex in Alzheimer's disease.

Posterior cingulate cortex is the site of earliest reductions in glucose metabolism and qualitatively different laminar patterns of neurodegeneration in Alzheimer's disease (AD). This study used multivariate analyses of area 23 in 72 cases of definite AD to assess relationships between laminar patterns of neurodegeneration, neurofibrillary tangle (NFT) and senile plaque (SP) densities, age of disease onset and duration, and apolipoprotein E (ApoE) genotype. No age-related changes in neurons occurred over four decades in 17 controls and regression analysis of all AD cases showed no relationships between neuron, SP, and tau-immunoreactive NFT densities. Principal components analysis of neurons in layers III-Va and eigenvector projections showed five subgroups. The subgroups were independent because each had a full range of disease durations and qualitatively different laminar patterns in degeneration suggested disease subtypes (ST). Cases with most severe neuron losses (STSevere) had an early onset, most SP, and highest proportion of ApoE epsilon4 homozygotes. Changes in the distribution of NFT were similar over disease course in two subtypes and NFT did not account for most neurodegeneration. In STII-V with moderate neuron loss in most layers, cases with no NFT had a disease duration of 3.5 +/- 0.9 years (mean +/- SEM), those with most in layers IIIc or Va had a duration of 7.3 +/- 1 years, and those with most in layers II-IIIab had a duration of 12.1 +/- 1 years. In STSevere, cases with highest NFT densities in layers II-IIIab also were late stage. Finally, epsilon4 homozygotes were most frequent in STSevere, but four statistical tests showed that this risk is not directly involved in neurodegeneration. In conclusion, multivariate pattern recognition shows that AD is composed of independent neuropathological subtypes and NFT in area 23 do not account for most neuron losses.

Laser microprobe mass spectrometric study of aluminum and silicon in brain emboli related to cardiac surgery.

Recent investigations have shown numerous fatty microemboli, which we previously termed small capillary and arteriolar dilatations (SCADs), in brain microvessels of patients who died after cardiac surgery assisted by cardiopulmonary bypass (CPB). The hypothesis of this study was that extraneous trace elements such as aluminum (Al) and silicon (Si) might be contaminating the blood and causing the formation of SCADs or coating the SCADs already formed in the extracorporeal circulation during CPB. Small capillary and arteriolar dilatations were identified in thick celloidin sections of the brains of 8 patients who died after cardiac surgery supported with a membrane oxygenator, and of 2 dogs that underwent CPB with a bubble oxygenator. The sections were infiltrated with Spurr's embedding medium for electron microscopy. Resin sections 0.5 microm thick were placed on 100-mesh copper grids and analyzed with laser microprobe mass spectrometry. Brain sections without SCADs from 3 patients (controls) whose deaths were not related to cardiac surgery were processed similarly. In SCADs and nearby neuropil sites of the 8 patients who had cardiac surgery, both Al and Si values were higher than in the neuropil, including vessels of the 3 controls. Si values were also high in the 2 dogs, in which a bubble oxygenator was used. Our results indicate that contamination with Al and Si continues to occur during cardiac surgery assisted by CPB. Our data also suggest that switching to membrane oxygenators from bubble oxygenators for CPB may have reduced Si contamination of blood. Further refinements of CPB aimed at eliminating microemboli formation and Al and Si entry into the circulation are warranted.

Solitary fibrous tumor of the meninges.

The clinical, radiologic, and pathologic features of a case of solitary fibrous tumor of the meninges at the base of the brain are reported. The tumor caused clinical symptoms in a 42-year-old Caucasian male which were indicative of compression of hypothalamus, basal ganglia, and third ventricle. Radiologically it was a large extra-axial mass isointense to brain parenchyma on precontrast T1-weighted images that filled the suprasellar cistern and deformed the left cerebral peduncle. At surgery, the tumor was firm to hard and attached to dura. Histologically the tumor was composed of spindle-cell proliferation in a collagen-rich background but exhibited regional variations. CD34 immunoreactivity was a prominent histologic finding. Ultrastructural features of meningioma, such as complex interdigitation of cell processes and intercellular specialized junctions were absent. The cells showed the typical appearances of fibroblasts with proximity of banded collagen and precollagen and cytoplasmic rough-surfaced endoplasmic reticulum. DNA ploidy analysis showed diploid DNA content. Awareness of this neoplasm may lead to increasingly frequent recognition and the current WHO classification of brain neoplasms should be modified to include this new entity.

Immunohistochemical assessment of constitutive and inducible heat-shock protein 70 and ubiquitin in human cerebellum and caudate nucleus.

The distributions of constitutive and inducible 70-kDa heatshock proteins (Hsc70 and Hsp70, respectively) and ubiquitin (Ub) were investigated in autopsy specimens from 24 adult human brains. The objectives were to verify that the milder fixation and celloidin embedding applied to those specimens preserved protein immunoreactivity in the tissue sections, even with extended intervals between death and fixation, and to determine the typical pattern of distribution of the proteins in aged human cerebellum and caudate nucleus. To achieve these objectives, the patterns of immunoreactivity in human specimens were compared with those in normal rat brain after three methods of immersion fixation: 1. 1% Formalin; 2. 10% Formalin; 3. Methacarn (a modification of Carnoy's solution). Additionally, some rats were left refrigerated, but unfixed for up to 24 h to mimic the postmortem interval that commonly occurs prior to fixation of human autopsy material. Tissues were embedded in celloidin, sectioned at 100 microns, and the celloidin dissolved to permit immunostaining. Immunoreactivity for all antigens was greatly diminished in the rat brain by fixation in 10% formalin compared to 1% formalin or methacarn. Rat and human brain tissues fixed in the latter two solutions showed similar patterns of low levels of Hsp70 immunostaining in gray matter and other areas where neuronal somata were concentrated, whereas Hsc70 immunostaining was much greater in those same areas. Little Hsc70 or Hsp70 immunoreactivity was detected in the white matter from either source, but immunoblots of human gray and white matter suggested that white matter contained more Hsc70 and Hsp70 than apparent by tissue section immunoreactivity. Ubiquitin immunostaining in rat and human brain showed the same high levels as Hsc70 in gray matter, but unlike Hsc70, was also visible in white matter. These patterns remained the same in rat brains even if fixation was delayed for 24 h. In three human brain specimens, elevated Hsc70 staining, but not Hsp70 or Ub, was found in a ring pattern similar to that described as the ischemic penumbra in experimentally induced brain ischemia. These results indicated that dilute formalin preserved Hsc/Hsp70 and Ub antigenicity well, and that the proteins had similar distributions in human and rat brains, despite the extended postmortem delay in fixation of the former. They also suggested that evidence of premortem, localized cellular metabolic stress may be preserved in the postmortem human brain by an alteration in the typical distribution of Hsc70.

Cerebral microvascular alterations in aging, leukoaraiosis, and Alzheimer's disease.

We have been using alkaline phosphatase (AP) histochemical staining, formerly a research tool for the study of cerebral cortical vascular morphology, to examine pathological changes in the cortex and deep cerebral structures. Deep structures stain similarly to the cortex. The AP stain is found in the afferent vessels (small arteries, arterioles, and capillaries), but not in venules and veins. The stain is also present in leaky vessels, such as those in the area postrema. The vascular supply to the cerebrum is not homogeneous. Supply to the deep white matter, for instance, derives from the leptomeningeal border zone, and then medullary arterioles must wind their way for up to 4 cm before arriving at their ultimate destination. Adding to the difficulties, tortuosities develop in some of these vessels with aging. According to some calculations, hypertensive levels of blood pressure would be required to maintain irrigation through some of these vessels. We have identified a venous alteration that attends aging: periventricular venous collagenosis (PVC) is a previously unrecognized, noninflammatory, mural disease of the periventricular veins. In severe cases, examples can be found of veins that are completely occluded by this process. PVC is found in 65% of subjects over 60 years old, and it strongly correlates with leukoaraiosis. In addition to previously mentioned aging-related changes, we have found extreme tortuosity, multiplications, and aneurysms of the smallest arterioles and lumpy-bumpy capillaries in the deep structures of patients with Alzheimer's disease.

Human germinal matrix: venous origin of hemorrhage and vascular characteristics.

PURPOSE: To examine the vascular supply and architecture of the germinal matrix in the preterm neonatal brain and to determine whether veins or arterioles are the source of germinal matrix hemorrhage. METHODS: Brains from eight preterm neonates (24 to 35 weeks' gestation) and two full-term infants were fixed in alcohol, embedded in celloidin, sectioned at 100- and 500-micron thicknesses, stained for alkaline phosphatase, and examined with light microscopy. High-resolution contact radiographs of 500-micron-thick sections were also mounted on glass slides for microscopic examination. RESULTS: The upper and middle regions of the germinal matrix are supplied by branches of the lateral striate arteries, whereas the inferior part is supplied by branches of the recurrent artery of Heubner. In brain sections from four of the preterm infants, we found 15 circumscribed hemorrhagic foci within the germinal matrix. The largest was 5 mm in diameter; the smallest, 1 mm. All hemorrhages but one were closely associated with veins, with significant involvement of the perivenous space. The other hemorrhage appeared to be associated with an arteriole. In term and preterm infants, we found no arteriolar-to-arteriolar shunts, precapillary arteriolar-to-venules shunts, or vascular rete. At all gestational ages, the terminal vascular bed had only conventional branchings and connections. CONCLUSION: In preterm neonates, staining for endogenous alkaline phosphatase allows visual differentiation between afferent and efferent vessels. Germinal matrix hemorrhage in preterm neonates is primarily venous in origin. A hemorrhage can tunnel along the venous perivascular space, collapsing the vein and rupturing the tethered connecting tributaries. Extravasation of blood from the arterial circulation appears to be much less common.

Neoplasms of the pineal region.

Tumors of the pineal region are rare but pose interesting diagnostic and therapeutic challenges. A diverse group of neoplasms may occur in the pineal region, and correct histologic diagnosis is critical to proper management of the disease. To emphasize the need for tissue diagnosis, we present five cases of pineal region tumors, including germinoma, pinealoblastoma, pinealoma, astrocytoma, and meningioma. In addition, we discuss the differential diagnosis of pineal region tumors, emphasizing the histologic, prognostic, and therapeutic differences between various tumor types.

Pericytosis and edema generation: a unique clinicopathological variant of meningioma.

OBJECTIVE: We report a group of eight patients with a distinctive histological variant of meningioma that is associated with severe peritumoral edema. The clinical presentation, radiographic findings, and histology of this type of tumor may lead to misdiagnosis as an aggressive or malignant process. METHODS: We reviewed the histology from patients who had removal of meningiomas performed in our institution between 1978 and 1992. Tumors having abnormal proliferation of cells in the intramural vascular spaces were selected for study; case histories and radiographs were reviewed. Tumor material was subjected to special stains, immunocytochemical examination, and election microscopy. RESULTS: Several lesions were misread radiographically as being malignant. Patients underwent craniotomy with complete excision of the tumor. All lesions were small (< or = 3 cm), and no brain invasion, unusual tumor vascularity, or dural sinus involvement was noted in any case. Histologically, the meningioma pattern in each case was meningothelial and benign in appearance. The immunocytochemical and electron microscopic features of the unusual cells in the blood vessel walls are most consistent with their being of pericytic origin. All patients have remained asymptomatic and without evidence of tumor recurrence with follow-up from 3 to 12 years. CONCLUSION: These tumors showed proliferation of pericytes in blood vessel walls and represent a new subtype of meningothelial meningioma. The apparently benign nature of these lesions necessitates their recognition. Characteristic findings of pericytic proliferation associated with edema generation have led us to descriptively term this the PEG variant of meningioma.