Intraoperative imaging for remnant viability assessment in bilateral posterior retroperitoneoscopic partial adrenalectomy in an experimental model.

BACKGROUND: A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function. METHODS: Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer-assisted quantitative fluorescence imaging, contrast-enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy. RESULTS: Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments. CONCLUSION: In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands. Surgical relevance Preservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown. New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast-enhanced intraoperative CT showed congruent results in evaluation of perfusion. Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.

ANTECEDENTES: Un abordaje quirúrgico que preserve la función del tejido suprarrenal permite lograr la curación bioquímica, a la vez que evita la necesidad de tratamiento sustitutivo con corticoides de por vida. El objetivo de este estudio experimental fue evaluar el impacto de las técnicas de imagen intraoperatorias en la suprarrenalectomía parcial (partial adrenalectomy, AE) bilateral sobre la perfusión y función del remanente glandular. MÉTODOS: Cinco cerdos fueron sometidos a una división bilateral central de la glándula suprarrenal por retroperitoneoscopia posterior (n = 9, 1 sin dividir). Durante la intervención, la evaluación de la perfusión incluyó la fluorescencia con cuantificación asistida por ordenador (Realidad Aumentada basada en la Fluorescencia, FLuorescence-based Enhanced Reality, FLER), tomografía computarizada (computed tomography, CT), endomicroscopia con laser confocal (confocal laser endomicroscopy, CLE) y un muestreo local de lactato. El análisis de la pieza quirúrgica tras completar la AE (n = 10) incluyó actividad mitocondrial y microscopia electrónica. RESULTADOS: La evolución de la intensidad de la señal de fluorescencia a lo largo del tiempo (ΔI/s) fue significativamente más baja en el segmento craneal de cada una de las glándulas (0,052 ± 0,057 craneal versus 0,133 ± 0,057 caudal, P = 0,02). De forma concordante, la CT intraoperatoria en la fase portal demostró una captación de contraste significativamente más baja en los segmentos craneales (P = 0,03). En la CLE, el contraste de fluoresceína se observó en todos los segmentos caudales, pero solo en el 44% de los segmentos craneales (P = 0,04). Los hallazgos obtenidos en las pruebas de imagen favorables a la perfusión caudal fueron congruentes con niveles significativamente más bajos de lactato capilar a nivel local (11,58 ± 6,53 mmol/L craneal versus 5,66 ± 5,79 mmol/L caudal, P = 0,008). A nivel craneal, la microscopia electrónica mostró más células necróticas (P = 0,03). La actividad mitocondrial (tasas de respiración, especies reactivas de oxígeno y producción de H2 O2 ) no mostraron disparidad entre los diferentes segmentos. CONCLUSIÓN: En un modelo de AE parcial bilateral, las tres modalidades de pruebas de imagen intraoperatorias podrían discriminar de forma consistente una perfusión regular y reducida del remanente suprarrenal. Al evitar una disección circunferencial, se preservó la función mitocondrial en cada segmento de las glándulas suprarrenales.

Azathioprine as an alternative treatment in primary hypophysitis.

Primary hypophysitis (PH) is an unusual disorder characterized by inflammatory infiltration of the pituitary gland with various degree of pituitary dysfunction. Glucocorticoids are the treatment of choice in the majority of patients. Still, in patients with poor response in glucocorticoids or when their administration is accompanied with serious side effects, the use of alternative agents should be considered; up to now, data on other therapeutic approaches remains scant mainly due to the rarity of the disease. Among them, the immunosuppressant azathioprine could represent an effective and safe alternative. In this article, we present our clinical experience of two cases with PH successfully treated with azathioprine following serious side effects after initial treatment with glucocorticoids and provide a brief review of the existing literature.

Treatment of Rathke's cleft cysts: experience at a single centre.

Rathke's cleft cysts are rare benign lesions requiring surgical treatment when they become symptomatic. Transsphenoidal surgery is the recommended therapy due to its efficacy and safety. However, whether the optimal surgical strategy is simple drainage and biopsy or cyst wall resection remains controversial. We report a single center's experience of a series of 14 Rathke's cleft cysts treated with transsphenoidal resection of the cyst wall. Postoperatively, there was no cerebrospinal fluid rhinorrhea. The complications included permanent diabetes insipidus, hypocortisolism (including a patient with a coexisting adrenocorticotropic hormone-secreting adenoma), sinusitis and a case of meningitis and intrasellar abscess, one year post-surgery. Visual impairment and headache resolved in all cases. Pituitary dysfunction was restored only in patients with hyperprolactinemia and Cushing's disease. During the follow-up period (median 29 months) there was no recurrence requiring re-operation. According to our experience, the aggressive approach is associated with good surgical results and with low complication and recurrence rates.

Subependymomas of the lateral ventricle: tumor recurrence correlated with increased Ki-67 labeling index.

Subependymomas of the lateral ventricles are rare tumors. We present two patients with subependymomas of the lateral ventricle, who underwent gross total resection of the tumor via transcallosal approach. The patient, with increased Ki-67 labeling index had recurrence of tumor two years after the initial operation. We emphasize at the risk of recurrence which is probably correlated with Ki-67 labeling index.

Secondary involvement of breast with non-Hodgkin's lymphoma in a patient with HIV infection -- case report.

Secondary lymphoma of the breast is a rare entity in patients with non-Hodgkin's lymphoma (NHL). HIV infection is associated with an increased risk for developing NHL, however lymphomatous involvement of the breast in AIDS patients has rarely been reported. We present the case of a 33-year-old HIV-infected female patient with diffuse NHL who presented with a unilateral breast mass. Histologic examination of the biopsy specimen revealed a highly-malignant diffuse large B-cell lymphoma.

Hypophysitis superimposed on a non-functioning pituitary adenoma: diagnostic clinical, endocrine, and radiologic features.

Pituitary adenomas are common neoplasms requiring medical and/or surgical treatment when associated with hormonal hypersecretion. Treatment of non-functioning pituitary adenomas is necessary when symptoms of mass effect or hormonal deficits occur. However, therapeutic options, including surgical resection and/or radiotherapy, can be associated with significant complications. Hence, it is important to consider disorders that could present in a similar manner to pituitary adenomas, for which surgery is not the indicated therapeutic approach. We describe herein a 38-yr-old woman who presented with a pituitary lesion that was considered to be a non-functioning pituitary adenoma. Due to lack of hormonal deficits and/or compression of adjacent structures, we opted for conservative management and followup with consecutive magnetic resonance imaging. Fifteen months after initial diagnosis, considerable enlargement of the lesion was noted, extending mainly superiorly and indenting the optic chiasm. Repeated endocrine investigation revealed partial anterior pituitary insufficiency. The patient underwent trans-sphenoidal resection of the pituitary lesion; histology revealed a null cell pituitary adenoma and lymphocytic hypophysitis (LYH) of the non-neoplastic adenohypophysial gland. Post-operatively, complete anterior and partial posterior pituitary insufficiency developed. This case illustrates the effects of new-onset LYH in a patient with a pre-existing non-functioning pituitary adenoma. Being aware of this rare possibility is important, as enlargement of the pituitary lesion may not be caused by expansion of the preexisting tumor, but by the onset of LYH of the nonneoplastic pituitary tissue.

Laparoscopic adrenalectomy for large adrenal metastasis from contralateral renal cell carcinoma.

We present herein the case of a patient with solitary metachronous contralateral adrenal metastasis from renal cell cancer. The patient had undergone left radical nephrectomy and adrenalectomy for localized renal cancer 7 years previously. Laparoscopic transperitoneal right adrenalectomy was performed. The postoperative period was uneventful. Histology showed right adrenal metastasis from renal cancer. At 6-month follow-up, there was no evidence of recurrence.

Mapping of somatostatin receptor types in GH or/and PRL producing pituitary adenomas.

BACKGROUND: Somatostatin is a tetradecapeptide exerting inhibitory action on endocrine and exocrine cell secretion and proliferation. Somatostatin receptors (SST) are widely expressed in various neoplasms including endocrine tumours. Using immunohistochemistry, the expression of SST(1), SST(2A), SST(2B), SST(3), SST(4), and SST(5) was studied in tissue microarrays (TMAs), using a series of 90 human pituitary adenomas producing growth hormone and/or prolactin, including 30 of each somatotroph, lactotroph, and mixed somatotroph/lactotroph adenoma type. METHODS: For immunohistochemistry, the standard avidin biotin complex method enhanced by tyramide was used, using polyclonal antisera for all SST types. A four point scoring system was used to assess the membranous immunopositivity. RESULTS: All SST types were positive in all tumour types, showing varying immunoreactivity scores. SST(5) and SST(2A) were the predominant receptors, showing strong expression in high frequency in all three adenoma types. Strong expression of SST(1) was higher in lactotroph adenomas than in other tumour types. CONCLUSIONS: The immunohistochemical results of SST expression are in agreement with most findings of previous molecular studies. The fact that SST(2A) expression is predominant suggests that pharmaceutical octapeptide somatostatin analogues may act through this receptor, while the role of SST(2B) may be merely synergistic.

Ectopic bioactive luteinizing hormone secretion by a pancreatic endocrine tumor, manifested as luteinized granulosa-thecal cell tumor of the ovaries.

Endocrine pancreatic tumors are rare neoplasms consisting of multipotent cells capable of secreting various bioactive substances causing characteristic clinical syndromes. Ovarian stromal hyperthecosis is characterized by varying degrees of luteinized stromal cell proliferation after sustained LH and/or human chorionic gonadotropin stimulation, clinically manifested by symptoms/signs of virilization resembling the polycystic ovary syndrome (PCOS). We report a case of ectopic bioactive LH production from a pancreatic endocrine tumor in a 33-yr-old woman with rapidly developing symptoms/signs of hyperandrogenism and markedly elevated serum androgen and LH levels leading to hyperthecosis and bilateral luteinized granulosa-thecal cell tumors of the ovaries. Although the patient was initially thought to have either severe PCOS or an LH-secreting pituitary tumor, an LH-producing pancreatic endocrine tumor bearing somatostatin receptors was demonstrated on scintigraphy with [111In]octreotide and abdominal imaging. Symptoms and signs of hyperandrogenism resolved after the resection of the tumor. Immunohistochemistry, in situ hybridization, and electron microscopy studies confirmed LH synthesis by the tumor cell. Although extremely rare, ectopic LH production from nonpituitary endocrine tumors should be considered in the differential diagnosis of hyperandrogenism, particularly when associated with highly elevated serum LH levels.

Treatment with oral biphosphonates can increase the sensitivity of sestamibi radionuclide imaging in patients with primary hyperparathyroidism.

The sensitivity of 99mTc-sestamibi scan in detecting parathyroid disease in primary hyperparathyroidism (PHP) is almost 90%, and therefore facilitates successful parathyroidectomy. To enhance the diagnostic accuracy of the procedure, we repeated imaging with 99mTc-sestamibi in 15 patients with PHP and an initially negative (11 patients) or weakly positive (four patients) 99mTc-sestamibi scan after the administration of 10 mg of oral alendronate for 2 months. Serum calcium, phosphate and parathormone (PTH) measurements were obtained at presentation and after 1 and 2 months' treatment with alendronate. Eight patients with an initially negative 99mTc-sestamibi scan demonstrated at least one area of uptake in the repeated scan. Six of these patients underwent surgery and obtained a biochemical cure; a single adenoma was found in four and hyperplasia in the remaining two. In all four patients with an initially weakly positive 99mTc-sestamibi scan, the repeated scan demonstrated enhanced uptake and also revealed further areas of uptake. Two of these patients underwent surgery with a biochemical cure; an adenoma was found in one and hyperplasia in another. Compared with baseline there was a significant increase in PTH but not in calcium or phosphate levels during treatment with alendronate. We suggest that, in patients with PHP and a negative or weakly positive initial 99mTc-sestamibi scan, administration of oral alendronate may be associated with a positive repeated 99mTc-sestamibi scan and can thus enhance the sensitivity of the procedure.

Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings.

This report describes the clinicopathological features of 16 patients with lymphocytic hypophysitis and compares the results with the published literature. There were 2 males and 14 females in this series. In 10 of the 14 females (71%), the presentation was associated with pregnancy. Nine patients (56%) presented with symptoms of an expanding pituitary sellar mass, 10 (63%) had anterior pituitary hypofunction, 3 had diabetes insipidus (19%). Progressive undiagnosed hypopituitarism led to the demise of 3 patients (19%). Hyperprolactinemia was encountered in 6 patients (38%), and elevated growth hormone levels (GH) resulted in IGF-1 excess in one patient. Computed tomography (CT) and magnetic resonance (MR) imaging revealed features of a pituitary mass mimicking an adenoma in 10 cases (83%). Four patients (25%) had associated autoimmune thyroiditis. Morphologic examination of the pituitary and immunohistochemistry showed a polyclonal lymphoplasmacytic infiltrate as well as occasional neutrophils, eosinophils, and macrophages; the chronic inflammatory process resulted in focal or diffuse adenohypophysial destruction of variable severity with associated fibrosis. The inflammatory infiltrate involved the neurohypophysis in 2 cases and one of these patients had diabetes insipidus; the posterior lobe of two other patients with diabetes insipidus was not examined morphologically. We conclude that lymphocytic hypophysitis should be considered in the differential diagnosis of females with pituitary enlargement presenting in the peripartum period as well as those patients in whom pituitary hormone deficiency and/or excess is noted in association with a co-existing autoimmune disorder. This clinical suspicion should probably also be extended to include patients presenting with rapidly growing pituitary masses associated with compressive symptoms with or without pituitary hormone dysfunction. Because of the transient endocrine and compressive features of this condition in many instances, conservative treatment on the basis of clinical suspicion alone may obviate the need for aggressive pituitary surgery.

In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide.

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16% and to 24 +/- 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.

Molecular cytogenetics of chromosome 11 in pituitary adenomas: a comparison of fluorescence in situ hybridization and DNA ploidy study.

Chromosome 11 abnormalities were detected by fluorescence in situ hybridization (FISH) technique and compared with DNA ploidy in 24 surgically removed pituitary adenomas. The tumors were diagnosed and classified by histology, electron microscopy, and pituitary hormone immunocytochemistry. They included 2 densely granulated somatotroph (DG-SM) and 4 sparsely granulated somatotroph (SG-SM) adenomas, 3 SG lactotroph (LT), 2 mixed somatotroph-lactotroph (SM-LT), 4 functioning corticotroph (CRT), 1 silent CRT subtype 1, 1 thyrotroph, 1 mixed thyrotroph-somatotroph, 2 gonadotrophs, and 4 null cell adenomas. FISH analysis with an alpha-satellite DNA probe specific for chromosome 11 showed numerical abnormalities in 16 functioning (94%) and 5 nonfunctioning (71%) adenomas. Ten functioning tumors showed aneuploid histograms, whereas the remaining and all nonfunctioning adenomas were diploid. Aberrant chromosome 11 signals were noted mostly in aneuploid adenomas involving 17% to 100% of their cell population. The severity of chromosome 11 aberrations in adenomas containing extra copies often correlated with a higher DNA index (DI). Monosomy 11 as dominant aberration was noted in a mixed SM-LT and to a lesser degree in 3 CRT adenomas involving 21% to 97% of their cell population. Two of these CRT adenomas were associated with normal DI, whereas the remaining third showed a high DI, indicating increased copy number of chromosomes other than of chromosome 11. In conclusion, chromosome 11 abnormalities are common in all types of pituitary adenomas, occurring more frequently in functioning tumors. Specific numerical abnormalities, such as monosomy and trisomy, tend to be associated with certain adenoma types, whereas tumors with extra chromosome 11 copies often exhibit aneuploid histograms.

Double adenomas of the pituitary: a clinicopathological study of 11 tumors.

Of more than 3000 cases of surgically removed pituitary adenomas, 11 were defined as "double adenomas," i.e., 2 morphologically or immunocytologically distinct tumors. In 8 cases, the lesions exhibited differing histological features and immunophenotypes; in 2 specimens, distinct ultrastructural features were noted as well. In another instance, despite histological and immunocytological uniformity, the two neoplastic components demonstrated distinct ultrastructure. In yet another case, the two adenomas were consecutively removed; despite similar histological features, they differed in immunocytological and ultrastructural characteristics. Last, in one case, the adenoma was histologically uniform, but a portion of the mass exhibited immunoreactivity by ultrastructural features distinct from those of the remainder of the lesion. Hormonal excess attributed to both tumors could be correlated with endocrine manifestations in two cases. Double adenomas of the pituitary occur infrequently. In routine histological sections of surgical material, they are often difficult if not impossible to identify. Presented herein are clinical and endocrinological data on 10 cases of double pituitary adenomas correlated with morphological and immunocytochemical results. The literature regarding multiple adenomas is reviewed as are the diagnostic and therapeutic difficulties associated with these rare lesions.

Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications.

In a review of autopsy material from two centers, 20 pituitary glands were found containing multiple adenomas. In total, 44 adenomas were identified histologically; 16 glands contained double tumors and in four glands triple adenomas were found. Size was measured in 30 tumors, all of which were microadenomas. Thirty-four adenomas were located in the lateral wings and 10 lay in the median wedge. Forty-one tumors were chromophobic and three were basophilic. Immunocytochemical analysis of the 44 tumors demonstrated the presence of prolactin in 11, adrenocorticotropic hormone in three, growth hormone in one, and alpha-subunit as well as follicle-stimulating hormone and luteinizing hormone in one. Of the 20 patients studied, there were 11 men and nine women, with an average age of 69 years. All patients died from various nonendocrine causes. With the exception of one patient who appeared mildly acromegalic, no correlation was observed between pituitary morphology and clinical data. This study found a 10.4% frequency of adenomas in pituitaries studied randomly at autopsy. Multiple tumors were encountered in 0.9% of cases. Despite its low frequency, adenoma multiplicity may underlie surgical failure in cases in which one adenoma is removed and the other is left behind.

Intrasellar chordomas mimicking pituitary adenoma.

OBJECT: Whereas chordomas involving the sellar region are uncommon, largely or entirely intrasellar examples are rare. The goal in this study was to present examples of these rare tumors as a guide to their proper diagnosis and treatment. METHODS: The authors report three cases in which the chordomas filled the pituitary fossa and presented as nonfunctioning pituitary adenomas. All lesions exhibited the typical histological patterns and immunophenotype of chordoma. One tumor, studied ultrastructurally and subjected to DNA analysis, was shown to have a diploid histogram. The authors present a clinicopathological study of these three cases and review the literature on intrasellar chordomas. CONCLUSIONS: Although these tumors are easily misdiagnosed and therefore may not receive optimal treatment, aggressive surgical resection can yield a favorable prognosis in lesions with a limited extent.

Expression of leukemia inhibitory factor in craniopharyngioma.

It has recently been reported that overexpression of leukemia inhibitory factor (LIF) in mice transgenic for LIF causes invagination of the anterior wall of Rathke's pouch leading to the formation of cysts lined by LIF immunoreactive epithelial cells. Strong immunoreactivity was also found in human Rathke's cleft cysts. Because such cysts and craniopharyngiomas share a common histogenesis, we raised the question of whether LIF is also expressed in craniopharyngioma.Fourteen histologically verified craniopharyngiomas of adamantinomatous type were examined for LIF immunoreactivity using the streptavidin-biotin-peroxidase complex method. Rabbit-anti-LIF antibody dilution 1:40) was applied to tissues having undergone antigen retrieval (microwaving in citrate buffer at pH 6). For positive control, nontumorous pituitary tissues were used. Primary antibody substituted with phosphate-buffered saline served as a negative control.By immunocytochemistry, the epithelial cells of all 14 craniopharyngiomas were LIF immunoreactive, showing varying degrees of staining intensity. In comparison, the connective tissue components of the tumors were immunonegative.Our study provides evidence that LIF is expressed in the epithelial cells of craniopharyngioma. Further investigation is required to elucidate the possible role of LIF in the development and progression of craniopharyngiomas.

A histological and immunoenzymatic study on the histogenesis of "giant cell tumor of bones".

We carried out a prospective histologic and immunoenzymatic study, using lysozyme and AI-antichymotrypsin, of 15 well documented cases of giant cell tumors of bones. The histologic appearance of the majority of the tumors was characterized by great pleomorphism. The predominant histologic patterns could be classified as either fibroblastic or histiocytic. Mitoses were seen exclusively on stromal mononuclear cells. All tumors showed positive marking with both lysozyme and AI-antichymotrypsin. The enzymatic activity was more pronounced in areas of conventional histology and appeared as coarse orange-brown granules in the cytoplasm of many mononuclear and multinucleated giant cells. Enzyme-positive cells were less frequently found in fibroblastic areas of the tumor and especially in areas with minimal differentiation. The results indicate that giant cell tumor of bones may result from the neoplastic proliferation of mononuclear cells which in many areas of the tumor differentiate to either fibroblasts or histiocytes. Thus, giant cell tumor of bones may be analogous to fibrohistiocytic tumors of soft tissues.

Mucous metaplasia of epithelial cells in fibrocystic disease of the breast. A histochemical study.

Mucous metaplasia of breast epithelium was studied by histochemical procedures in cases of fibrocystic disease. Epithelial mucins consist almost entirely of non-sulfated sialomucins. A slight amount of sulfated sialomucins was identified occasionally while neutral mucins seems to be absent. Abundant glycogen granules are contained in the cytoplasm of metaplastic cells. The secretion of sialomucins may be associated with a loss of cell antigenicity. In this case, the survival of metaplastic epithelium supports the hypothesis of the possible immunological nature of the disease.

Duct elastosis in infiltrating carcinoma of the breast.

Duct elastosis was studied in 219 patients subjected to radical mastectomy for infiltrating carcinoma of the breast, with a 10-year follow-up. Duct elastosis is a frequent finding in infiltrating breast cancer (65% of our cases). It develops in tumors of all three grades of malignancy, but it is more frequent in tumors of low grade malignancy (76% and 74% in grades I and II, respectively, and 47% in grade III tumors). In spite of their greater incidence in low malignancy tumors, the elastotic cases have a greater metastatic ratio than the non-elastotic cases (66% vs 45%). The elastotic cases also contain a significantly greater proportion of scirrhous tumors than the non-elastotic cases (86% vs. 32%). Duct elastosis and scirrhous reaction are two processes which develop in parallel, but are not related etiologically. They seem to be correlated with more advanced stages of the neoplastic disease. The influence of duct elastosis upon the ten year survival of the patients is unfavorable. this influence is not direct, and it is particularly evident in the metastatic cases. It seems to be related to the greater duration of the neoplastic disease and to the slow clinical course of tumors of low degree of malignancy.