Extramedullary hematopoietic tumors of the posterior mediastinum related to asymptomatic refractory anemia.

Two asymptomatic paravertebral thoracic masses occurred in a 65-year-old patient with isolated macrocytosis. The largest one measured 8 cm and was surgically resected with a presumptive diagnosis of schwannoma. This thoracic mass was hemorrhagic, encapsulated, and composed of fat and hematopoietic tissue. While extramedullary hematopoietic tumors usually occur in patients with severe chronic hemolytic anemia, our report suggests that such lesions must be considered in the differential diagnosis of posterior mediastinal mass in patients without clinical evident anemia.

Germ cell tumors of the mediastinum. A 30-year experience.

BACKGROUND: The records of 98 consecutive patients (58 males and 40 females; median age, 27 years; age range, 2-64 years) who presented with a primary germ cell tumor (GCT) of the mediastinum between January 1960 and December 1990 were reviewed. There were 45 mature teratomas, 8 immature teratomas, 16 pure seminomas, and 24 malignant nonseminomatous GCT (MNSGCT). RESULTS: All patients with mature teratomas were cured by radical resection alone, except one patient who died intraoperatively. Among the eight patients with immature teratomas, five were treated before the advent of cisplatin treatment (two children younger than 15 years were cured by surgery alone and three adults died within 7 months after operation). Three patients underwent surgery followed by cisplatin-based chemotherapy (two are still alive and one died of an associated rhabdomyosarcoma). Thirteen of 16 patients with seminomas (81%) were cured by surgery either alone (5 patients) or with adjuvant radiation therapy (8 patients). Among the 24 MNSGCT, 10 were treated before 1980 without cisplatin and all but 1 died of disease progression. Fourteen patients were treated by initial high-dose cisplatin combination chemotherapy and 8 (57%) achieved complete remission (2 died of systemic mastocytosis development). CONCLUSIONS: Results indicate the benignity of mature teratomas of the mediastinum, the age-dependent clinical course of immature teratomas, and the excellent prognosis of seminomas. The improved survival advantage resulting from cisplatin-based chemotherapy in MNSGCT is impaired by the propensity to nongerminal solid tumor development and hematologic malignancies.

The secretory granule peptides 7B2 and CCB are sensitive biochemical markers of neuro-endocrine bronchial tumours in man.

OBJECTIVE: Bronchial tumours are the most frequent cause of the ectopic ACTH syndrome. Two types of tumours are classically responsible: the relatively benign carcinoids and the highly aggressive small cell carcinomas. Both have neuro-endocrine features and are thought to originate from the endocrine component of the bronchial tree. Our objective was to assess the sensitivity of 7B2 and secretogranin 1 as new biochemical markers of neuro-endocrine differentiation in these tumours in comparison with gastrin releasing peptide. METHODS: Tissue concentration of 7B2, secretogranin 1 fragments (GAWK and CCB), gastrin releasing peptide and beta-endorphin were measured in normal human lung (n = 4), bronchial carcinoid tumours with (n = 5) and without (n = 15) the ectopic ACTH syndrome, small cell carcinomas (n = 2), squamous cell carcinomas (n = 11) and adenocarcinomas (n = 6). Molecular weight forms of immunoreactive--ACTH, -GAWK, -gastrin releasing peptide, and -7B2 were also examined using gel exclusion chromatography and Western blot analysis. RESULTS: We detected 7B2 immunoreactivity in 19 of 22 neuro-endocrine lung tumours (with values ranging from less than 5 to 555 fmol/mg wet weight tissue), CCB immunoreactivity in 20 of 22 tumours with neuro-endocrine features (with values ranging from less than 5 to 19,875 fmol mg wet weight tissue) and gastrin releasing peptide immunoreactivity in 10 of 22 neuro-endocrine lung tumors (with values ranging from less than 5 to 11,132 fmol/mg wet weight tissue). Immunoreactive 7B2 and CCB were detected neither in tumours with non-endocrine features, nor in the four normal lung specimens. Differing molecular weight forms of immunoreactive 7B2 in two bronchial carcinoids associated with the ectopic ACTH syndrome showed a predominant signal corresponding to a molecular weight of 22 kDa; in addition, a second signal of 19 kDa was also present. The differing molecular weight forms of immunoreactive ACTH related peptides in the five tumours responsible for the ectopic ACTH syndrome showed, in addition to ACTH1-39, the constant presence in variable proportions of corticotrophin-like intermediary lobe peptide (or ACTH18-39). The differing molecular weight forms of immunoreactive GAWK showed heterogeneous results with materials eluting at Kav of 0, 0.3 and 0.4 respectively. In the three bronchial carcinoids studied, two immunoreactive gastrin releasing peptide molecular weight forms were always found at Kav of 0.5 and 0.85 corresponding to gastrin releasing peptide and its fragment 14-27 respectively. CONCLUSION: Our results show that 7B2 and the two fragments of secretogranin 1 (GAWK and CCB) are the best biochemical markers of neuro-endocrine differentiation in human lung tumours.

Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors.

The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease.

Proopiomelanocortin gene expression in normal and tumoral human lung.

Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation.

[Solitary plasmacytoma of the trachea. Apropos of a case]. / Plasmocytome solitaire de la trachée. A propos d'un cas.

A case of solitary plasmacytoma of the trachea is reported. Immunohistochemical study is mandatory to prove a monoclonal immunophenotyping. Research for signs of systemic disease and follow up over a long period of time are indicated. Surgery alone, sometimes followed by irradiation, seem to be the treatment of choice. In most cases, complete resolution is observed.

[Histopathology and prognosis of thymomas. Statistical analysis of 200 cases]. / Histopathologie et pronostic des thymomes. Analyse statistique de 200 cas.

200 cases of thymoma operated on at the surgical centre of Marie-Lannelongue between 1955 and 1982 were reviewed and analysed statistically; their histology was compared and their evolutionary potential. Based on their degree of differentiation of the epithelial tumour component and on the proportion of non tumour associated lymphocytes, 4 histological types were defined: 1) Spindle-or-oval-cell thymomas where tumour cells reminiscent of normal involutive thymic cells were of small size with a tendency to form clusters, whorls or a glandular appearance; 2) Lymphocyte-rich thymomas where normal epithelial cells, few in number, reproduce the appearance of normal thymic cells; 3) Differentiated epithelial thymomas, comprised of large epithelial cells with abundant cytoplasm and clearly demarcated and often less numerous lymphocytes; 4) Undifferentiated epithelial thymomas, characterised by a poverty of lymphocytes and anaplastic epithelial cells with a raised nuclear cytoplasmic ratio, nuclear irregularity and mitosis. Statistically, there was a significant correlation between the degree of differentiation of the tumor and prognosis. Spindle-or-oval cell thymomas (type 1) and lymphocyte-rich thymomas (type 2) have an 80% survival at 5 years and a 75% survival at 10 years. Well differentiated epithelial thymomas of type 3 have a 75% survival at 5 years and a 50% survival at 10 years, finally undifferentiated epithelial thymomas (type 4); the survival rate was nil at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex.

17 thymomas were studied by indirect immunofluorescence for the presence of thymic hormones and antigens of the major histocompatibility complex (MHC). The thymoma epithelial cells (specifically identified by their keratin content) contained thymic hormones (thymulin and thymosin alpha 1), a finding corroborated by the observation of elevated thymulin serum levels. In contrast with normal or hyperplastic thymuses, thymoma epithelial cells did not express HLA-DR and HLA-DC antigens as assessed by immunofluorescence as well as immunoblot analyses. Conversely, MHC class I antigens (HLA-ABC) were normally expressed. Thus, we conclude that thymoma epithelial cells are endocrinologically active but are defective for the expression of some MHC products (class II molecules) known to play an essential role in intrathymic T cell differentiation.

Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases.

Two hundred thymomas, surgically treated between 1955 and 1982 at the Marie Lannelongue Surgical Center, were subjected to statistical analysis, comparing clinical stages and histologic types and relating them to survival. Clinical stages were defined as follows. Stage I: no invasiveness, total excision; Stage II: localized invasiveness (no more than two mediastinal structures); Stage III: largely invasive, with or without distant tumorous grafts, lymph node deposits, or metastases. Four histologic types were retained: (1) spindle or oval cell type thymoma, (2) lymphocyte-rich thymoma, (3) differentiated epithelial thymoma, and (4) undifferentiated epithelial thymoma. Invasiveness remained a major prognostic factor, but the degree of invasion did not affect the survival rate or always justify radical surgery. Thus, the survival rate dropped from 85% at 5 years and 80% at 10 years in noninvasive tumors to 50% and 35%, respectively, in invasive tumors, but without significant difference between moderately invasive Stage II and largely invasive Stage III tumors. Histologic typing indicated a good correlation between the degree of differentiation of the tumors and prognosis. The survival rates were 80% at 5 years and 75% at 10 years for spindle cell type 1 and lymphocyte-rich type 2 thymomas, 75% at 5 years and 50% at 10 years for differentiated epithelial type 3, and nil at 5 years for undifferentiated type 4 thymomas. Although invasiveness often paralleled histologic typing, they appeared as two distinct parameters with separate prognostic significance, particularly in differentiated and undifferentiated epithelial tumors. One hundred five patients had myasthenia gravis and 14 had another autoimmune disease. The associated syndromes were no longer an adverse factor in the prognosis of thymoma.

[Anatomopathology, physiopathology and treatment of the emphysematous disease of infants (apropos of an experience with 133 surgically treated cases)]. / Remarque sur l'anatomopathologie, la physiopathologie et le traitement de la maladie emphysemateuse du petit enfant (à propos d'une expérience de 133 cas opérés).

Infantile and childhood lobar pulmonary emphysema (LPE) has finally become a rather straightforward problem after 28 years experience and the important statistics published. Contrary to adult emphysema, and leaving aside the particular aspects of causal lesions, the pediatric form is usually a unilateral lobar or infralobar disorder, and therefore lends itself to surgical treatment.

[Results and prognostic factors in surgically treated thymoma. Apropos of a series of 194 cases]. / Résultats et facteurs pronostiques des thymomes opérés. A propos d'une série de 194 cas.

The authors analyse a series of 194 thymomas (epithelial tumours of the thymus gland) which were operated over a period of about 25 years. The long term prognosis (70% 5 year survival and 60% 10 year survival) is examined in terms of the anatomo-surgical stage of the thymoma, the histological type of the tumour and the presence of associated auto-immune diseases. The authors recommend a more rigorous classification which takes into account both the anatomo-surgical and the histopathological findings so that the indications for post-operative mediastinal irradiation can be extended in a attempt to reduce the rate of distant recurrence of these tumours.

Immunological investigation and immunotherapy in patients operated on for breast carcinoma.

The tumor-host relationship is an essential factor in the onset, development, and recovery from malignancies. A basic consideration in the treatment of cancer patients must therefore be to understand this relationship and attempt to modify it in order to favor the host. We here discuss the results of a study of the immunologic status of 91 breast cancer patients. The use of a battery of tests with five subcutaneous hypersensitivity antigens allowed us to detect some differences in the immunological profiles of patients with or without lymph node involvement. The effect of an immunostimulant fraction prepared from Corynebacterium granulosum, P40 is also analyzed. This fraction significantly modifies tumoral recurrence in DMBA-induced mammary cancers in the Sprague Dawley rat, causes regression of mammary permeation nodules following in situ injection and modifies the cutaneous reactions of one-half of the anergic breast cancer patients although regular re-challenge is still necessary.

[Ultrastructural study of small cell carcinoma (author's transl)]. / Diagnostic ultrastructural des cancers anaplasiques à petites cellules.

Fifty bronchopulmonary tumors were studied by light and electron microscopy: 39 carcinomas (25 small cell carcinomas, 8 undifferentiated carcinomas, 6 poorly differentiated squamous cell carcinomas) and 11 carcinoid tumors (5 central, 4 peripheral, 1 atypical, 1 of the tumorlet type). The results indicate that small cell carcinoma is a precise entity characterized by the presence of neurosecretory granules in the cytoplasm. Ultrastructurally carcinoid tumor resemble small cell carcinomas and there is a continuous spectrum of differentiation between the less undifferentiated neuro-endocrine tumors, i.e. the small cell anaplastic carcinomas, and the higher differentiated types, i.e. the carcinoids. The diagnostic and prognostic value of the ultrastructural findings are discussed.

Histopathology of the thymus of patients with acute lymphoblastic leukemia and lymphoblastic lymphoma in complete clinical remission.

The histologic features of thymuses from three patients who underwent thymectomy for acute lymphoblastic leukemia or lymphoblastic lymphoma in complete clinical remission are described. The thymuses from all three patients were fibrotic with a variability in the appearance of the lobules. Some of the lobules consisted predominantly of epithelial cells with small numbers of mature appearing lymphocytes, while other lobules were expanded and composed predominantly of cells having morphological features of immature lymphoid cells consistent with residual or recurrent disease.

Histopathological modifications following immunotherapy with P 40 in rats bearing DMBA-induced mammary carcinoma.

Female Sprague-Dawley rats bearing primarily-induced mammary carcinomas were treated with a new immunostimulating agent (P 40). The histopathological modifications encountered in tumors, lymph nodes, liver and spleen are described. Intratumoral injections provoke a more widespread response of the RES, and particularly a more intense reaction in the draining lymph nodes, than systemic treatment.