Denosumab use in bone fibrous dysplasia refractory to bisphosphonate: A retrospective multicentric study.

INTRODUCTION: Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates. MATERIALS AND METHODS: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS). RESULTS: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good. DISCUSSION: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS. CONCLUSION: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.

Analysis of 676 cases of ductal carcinoma in situ of the breast from 1971 to 1995: diagnosis and treatment--the experience of one institute.

Six hundred seventy-six patients with ductal carcinoma in situ of the breast (DCIS) from 1971 to 1995 were included in the study. Computerized patient files were retrospectively analyzed. Clinical findings were less frequently reported to reveal DCIS after 1989. Positive mammographic findings were obtained in 87% of patients and were mainly represented by microcalcifications (79.4%). Treatment procedures were breast-conserving surgery (BCS) alone (37.5%), BCS followed by radiation (BCSR) (25.5%), or mastectomy (M) (37%). The actuarial local recurrence was 2.6% in the M group (94 months of follow-up), 14.5% in the BCS group (85,7 months of follow-up), and 7.5% in the BCSR group (78.8 months of follow-up). Predictive factors of recurrence in all patients were invaded margin status and age. In the BCS group, grade was also a predictive factor. The analysis per decade shows that the lesions currently diagnosed are less serious than those of the past. All the recurrence in patients with positive margins was in the same quadrant as the original lesion. This further emphasizes the need for clear margins.

Application of the van nuys prognostic index in a retrospective series of 367 ductal carcinomas in situ of the breast examined by serial macroscopic sectioning: practical considerations.

UNLABELLED: The Van Nuys prognostic index (VNPI) was thought to be useful for predicting response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS). We applied the VNPI under the conditions defined by Silverstein et al., in 367 retrospective DCIS entirely sectioned into serial macroscopic 2 mm slices (155 patients had radiotherapy, median follow-up 71 months). The percentage of positive blocks with DCIS was also estimated for each specimen with cut-offs at 30% and 60% to obtain three scores. One hundred and ninety five lesions had a low VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local recurrences (half invasive, all in the group without radiotherapy) in the low VNPI group. The local recurrence rate increased with size (p = 0.001), with reduction of distance to margins (p = 0.05), with histologic grade (p = 0.02), with percentage of positive blocks (p = 0.0003) and with VNPI score (p = 0.03). The percentage of positive blocks was the only independent predictor for local recurrence (p = 0.0001). CONCLUSION: (1) The VNPI was a local recurrence rate predictor between the low and the intermediate groups but in our series the low VNPI group had a surprisingly high local recurrence rate. (2) Only prospective studies will assess the importance of margin width and the role of radiotherapy in maintaining local control. (3) Estimation of the percentage of positive blocks is simple, may be an alternative when measurement of DCIS is difficult and should be taken into account.

Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases.

To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p53 were additionally considered as prognostic variables. The median follow-up time was 149 months. Eight-hundred-and-sixty-three tumors reacted with Ki-S11 and Ki-S4; the labeling indices of the two antigens were closely associated (r = 0.93). Both correlated positively with the tumor size, c-erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki-S11 and Ki-S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis-free survival (p < 0.00001). Estrogen receptor status, p53, and c-erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki-S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki-S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki-S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIalpha expression as assessed by monoclonal antibody Ki-S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.

Familial non-medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families.

BACKGROUND AND OBJECTIVES: When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC. PATIENTS AND METHODS: Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed. RESULTS: Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous. CONCLUSION: Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.

[Recurrence after treatment of breast intraductal carcinoma]. / Les récidives après traitement des carcinomes intracanalaires du sein.

OBJECTIVE: To assess the risk of local recurrence of intraductal carcinoma of the breast with a large series and a review of literature. METHODS: We present a retrospective study of 331 cases treated for intraductal carcinoma of the breast. Only patients with at least 5 years follow-up were selected. We were specially interested in recurrence risk factors. In these patients with a long follow-up; pathology was reevaluated with new investigation technique. RESULTS: After a median follow-up of 109 months, 40 local recurrences were observed; these lesions were invasive in 23 cases. Only one patient had recurrence after mastectomy. For the others, they had lumpectomy associated with radiotherapy in 12 cases. Histologic features, grade and therapeutic options were evaluated as risk factors of local recurrence. CONCLUSION: Follow-up after lumpectomy for intraductal carcinoma was studied. The status of tumor margins was important; irradiation appeared useful, specially in case of high grade carcinoma but further large prospective randomized studies are needed. The use of prognostic index is interesting, but there are still unanswered questions.

Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers.

This study was conducted to determine the prognostic influence of obvious peritumoral vascular emboli as prospectively determined by a simple routine slide examination in patients with operable node-negative breast cancer. Obvious peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within unequivocal vascular lumina (including both lymphatic spaces and blood capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE were assessed routinely on 5 microns thick haematoxylin and eosin-stained sections for each of 1320 primary operable node-negative breast cancers from 1975 to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR grade, oestrogen and progesterone receptor status) were correlated to overall survival (OS) and metastasis-free interval (MFI) by means of univariate and multivariate analysis with a median follow-up of 103 months. OPE were found in 19.5% of tumours. In univariate analysis, OPE were related to tumour size (P = 6.3 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P = 7.7 x 10(-7)) before tumour size and grade, and was second after tumour grade for OS (P = 0.002). This study on a large unicentric series and with a long follow-up confirms the prognostic significance of vascular emboli in patients with operable node-negative breast carcinoma. Importantly, vascular emboli were found to be accurately detectable by a simple routine and non-time-consuming method. Therefore, such obvious vascular emboli should be considered as an important cost-effective, prognostic variable in patients with node-negative breast carcinoma.

[Mediastinal large B-cell lymphoma. A retrospective anatomic-clinical study of 26 cases]. / Lymphomes médiastinaux à grandes cellules B. Etude anatomoclinique rétrospective de 26 cas.

Mediastinal B-cell lymphomas (with or without sclerosis) have been recently recognized as an entity with particular clinical features. We report 26 patients with a mediastinal large B-cell lymphoma. They represent 5% of the patients with aggressive non-Hodgkin's lymphoma and 2% of all non-Hodgkin's lymphoma seen in our centre between 1962 and 1990. They include 19 females (73%) and 7 males (27%). The sex ratio was 2.7 and the median age was 44 years (range: 17-84 years). Compressive symptoms in relation with a bulky mediastinum were present in 21 cases (80%) and with B symptoms in 5 cases. All these patients received 2 to 4 cycles of chemotherapy with a CHOP-like protocol (epirubicin or doxorubicin, cyclophosphamide, vincristine and prednisone) followed in 24 cases by mediastinum irradiation (40 Gy). Two patients progressed during chemotherapy and did not receive radiotherapy. Nineteen patients had a consolidation chemotherapy according to the same protocol. Twenty-one patients achieved a complete remission after chemotherapy or radiotherapy and 5 failed. Two patients relapsed at 10 months and 9 years. Seventeen patients are alive and in first complete remission with a median follow-up of 102 months (range: 60-260 months). Using the Kaplan-Meier method, the overall survival at 5 and 10 years was respectively 77 and 61% and the relapse-free survival was respectively 68 and 57%. These results confirm the previous findings concerning this distinct entity which is characterized by a predilection for young women, compressive symptoms, a slow response to treatment and a rather good prognosis.

[Outcome of 111 thyroid papillary carcinomas. Retrospective study from 1953 to 1994. Experience of Bergonié Institute]. / Evolution de 111 microcarcinomes papillaires thyroïdiens. Etude rétrospective de 1953 à 1994. Expérience de l'institut Bergonié.

The evolution of techniques has increased the number of diagnosed thyroid papillary microcarcinoma challenging the previous therapeutic guidelines. We have studied all thyroid cancers in our data base (from 1953 to 1994, N = 698). One-hundred and eleven were papillary microcarcinomas (none before 1967): 83 M0N0, 24 M0N+ et 4 M+. One-hundred and eight pathologic slides could be obtained and were checked by one of us (pathologist). The mean follow-up was 8.6 yr [1-28]. Two clinical and pathological features were different between M0N0 and M0N+ (groups: i) the sex-ratio, 12 vs 50% men (M0N0 vs M0N+, p < or = 0.0001), ii) the invasiveness of the tumor, 54/83 vs 20/24 (M0N0 vs M0N+, p = 0.01). All patients received a suppressing treatment by thyroid hormones (except lobectomy). The other treatments were: for 64/83 M0N0 a total thyroidectomy followed by a I131 treatment, for the remaining no I131 (15 partial thyroidectomies and 4 total thyroidectomies). None of the M0N0 patients displayed metastasis or cancer relapse. All patients M0N+ had a total thyroidectomy followed by a I131 treatment. Among the latter, I had a major node evolution, the death was attributed to the cancer at the age of 83 after a 6 yr long evolution. Among the 4 patients considered as metastatic. 1 was poorly differentiated. For the remaining 3, the thyroidal origin of the metastasis was not clear. In summary, the papillary microcarcinomas display a good prognosis if devoid of metastasis. We propose the following guidelines: a total thyroidectomy followed by a I131 treatment and suppressing treatment if clinical nodes, or non-encapsulated tumor or multifocal tumor. For solitary tumors, well encapsulated a lobectomy appears sufficient.

Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi.

Primary chemotherapy in operable breast invasive carcinoma enables tumour reduction and conservative surgery. In order to search for one or more biological factors capable of predicting tumour behaviour under primary chemotherapy, and subsequent patient survival, an immunohistochemical study was performed with specific antibodies to p53, c-erbB-2 (Her-2/neu), Mib1 (antiKi-67), pS2, GST pi, oestrogen receptors (ERs) and progesterone receptors (PRs). Core biopsies, obtained before primary chemotherapy, were available from a series of 128 breast invasive carcinomas treated between January 1985 and April 1989, with a median follow-up of 93.3 months. Univariate statistical analysis showed that negative ER detection by immunohistochemistry (IHC) was highly correlated with chemosensitivity (P = 0.001). A high percentage of Mib1-positive tumour cells (> 40%), as well as initial tumour size less than 4 cm, were also correlated with tumour responsiveness to chemotherapy (P = 0.009 and P = 0.03). By multivariate analysis IHC-ER, Mib1 and initial tumour size were independent predictors, the last parameter being the most important. Concerning subsequent patient survival, c-erbB-2 overexpression, as detected by IHC, was significant with respect to overall survival (OS) (P = 0.0006), disease-free interval (DFI) (P = 0.03) and metastasis-free interval (MFI) (P = 0.008) by univariate analysis. Furthermore, c-erbB-2 was the major independent prognostic factor for OS and MFI by multivariate analysis.

Is there any place for a wait-and-see policy in stage I0 follicular lymphoma? A study of 43 consecutive patients in a single center.

BACKGROUND: A wait-and-see policy (WS) does not appear to modify the long-term prognosis of advanced-stage follicular lymphomas (FL), while irradiation of limited stages sometimes causes complications and does not avert distant relapses. Consequently, we decided to test WS in a selected subset of the localized FL, i.e., patients in complete remission (CR) after the initial lymph node biopsy (stage I0). PATIENTS AND METHODS: Forty-three previously untreated patients were diagnosed with stage I0 FL and 26 of them were included in the WS. Their median age was 60.3 years; 19 were male and 24 female. All histological slides were reviewed and confirmed the diagnosis of FL. Median follow-up was 6.3 years (y). RESULTS: Thirteen of the 26 untreated patients are still relapse-free, while six relapsed locally only (median: 4.2 years after diagnosis), and reattained CR with radiotherapy. Seven patients relapsed at distant sites (median: 1 year after diagnosis). No localized relapses were observed in the treated group, but there were 7 distant relapses. CONCLUSIONS: The use of WS in stage I0 FL did not appear to modify the prognosis of these patients. Furthermore, we observed two distinct patterns of relapse (local and distant) that are difficult to differentiate at onset.

Familial cluster of ovarian small cell carcinoma: a new mendelian entity?

We report a pedigree in which three sisters had a particular type of ovarian cancer, small cell carcinoma of the hypercalcaemic type. This rare type of ovarian carcinoma is now well characterised by clinical and pathological findings and is well distinguished from other ovarian epithelial tumours and ovarian germ cell tumours. The occurrence of this rare type of cancer in several members of the same family and the existence of four other similar published observations raises the question of the genetic determination of this kind of tumour.

CD30-positive cutaneous large cell lymphomas. A comparative study of clinicopathologic and molecular features of 16 cases.

The authors have analyzed and compared the clinicopathologic and molecular features of 16 cases of large cell cutaneous lymphomas expressing CD30 antigen. Three main clinical groups were defined: (1) a group of localized skin disease (7 cases); (2) a group of multicentric skin disease (5 cases); and (3) a group of concomitant skin and extracutaneous disease. Good prognosis was associated with localized skin disease and no history of lymphoma. Interestingly, a majority of Reed Sternberg-like cells was only observed in this group (5 of 6 cases). The two other groups did not show distinctive evolutive nor morphologic features. Southern blot and/or polymerase chain reaction (PCR) technique showed clonality and a T-cell genotype in respectively 13 of 14 and 12 of 12 analyzed cases. Viral infection of tumoral cells was investigated by PCR, in situ hybridization (ISH) or electron microscopy. Epstein-Barr virus (EBV) sequences were detected by PCR and ISH in tumoral cells of cutaneous lesions in one case of skin lymphoma with extracutaneous spreading. No EBV sequence was detected by ISH in the localized lymphomas, whereas HIV particles were visible in tumoral cells in one of these cases. No human T-cell lymphotropic virus (HTLV) tax sequence was amplified by PCR in any case of our series. Our results confirm that CD30-positive cutaneous large cell lymphomas are different clinical and molecular entities. However, a combined clinical and morphologic analysis may help to identify a subset of CD30 cutaneous lymphomas with favorable prognosis.

Transanal electroresection of small rectal cancer: a sole treatment?

PURPOSE: Because abdominoperineal resection is associated with high morbidity and mortality, there is interest in local treatment of distal rectal carcinoma. Our technique of transanal electroresection ensures full-thickness tumor excision and complete histopathologic examination. METHODS: From July 1983 to July 1990, 227 patients underwent surgery. Criteria for cure were no extramural invasion (61 exclusions) and negative margins (34 exclusions). Six patients underwent postoperative radiotherapy and, therefore, were excluded. RESULTS: Among those included were 126 patients (66 men), who had a mean age of 68 +/- 11 (median, 68) years. Median tumor size was 35 mm. Distance from anal verge was less than 6 cm for 68 percent and 6-10 cm for 30 percent of patients. Deepest layer invaded was as follows: submucosa (T1), 35 percent; inner muscular layer (T2a), 42 percent; outer muscular layer (T2b), 23 percent. There was one postoperative death. Immediate postoperative course was uneventful for 94 percent of patients; at long-term, five cases of incontinence and two stenoses were noted (6 patients). Median follow-up was 88 (1-137) months. Global survival was 71 and 46 percent, and cancer-specific survival was 85 and 81 percent at 5 and 10 years, respectively. Of 35 patients (28 percent) with recurrence, 24 were treated. Global survival after recurrence was 72 and 50 percent at one and two years, respectively. The only pejorative prognostic factors isolated for survival or recurrence were mucinous contingent and intratumoral vascular invasion. CONCLUSION: Results of local treatment for rectal carcinoma in selected patients are favorable (5-year specific survival, 85 percent). Decisive prognostic factors are seldom isolated, but some patients would benefit from adjuvant therapy.

The prognostic value of c-erbB2 in primary breast carcinomas: a study on 942 cases.

To assess the practical prognostic value of c-erbB2, we performed a study on 942 invasive ductal carcinomas treated with primary surgery between 1980 and 1986 in our center. We evaluated its expression by immunohistochemistry in paraffin-embedded tissue using a polyclonal antipeptide antibody. Of 942 tumors, 229 (24%) showed a positive membrane staining. We observed a significant association between c-erbB2 and Scarff-Bloom-Richardson grading (p < 0.0001) and a negative correlation between c-erbB2 and both estrogen and progesterone receptors (p < 0.0001). In our analysis, with respect to overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS), c-erbB2 was statistically significant (p < or = 0.0001) for the whole group and the node-positive subgroup. In multivariate analysis, c-erbB2 appeared to be an independent variable for RFS and MFS in the node-negative group. However, in our hands, c-erbB2 had a poor prognostic value in comparison with the classical prognostic variables such as histological grade, nodal status (N), hormonal receptor status (estrogen and progesterone receptors), and tumor size, and it did not supersede the classical parameters.

Immunohistochemical determination of pS2 in invasive breast carcinomas: a study on 942 cases.

To assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemistry in paraffin-embedded tissue from 942 previously untreated invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986. Positive staining of tumor cells was found in 684 cases (73%), but most of the tumors contained only a small amount of positive cells. There was a negative correlation between pS2 and tumor size (p = 0.01) and histological grade (p < 0.0001), and a positive correlation between pS2 and hormonal receptor status (p < 0.001). With respect to overall survival, pS2 positivity was associated with a better prognosis for the whole group and the node-positive sub-group. However, in terms of relapse and metastasis, pS2 was not significant. Furthermore, in multivariate analysis including tumor size, nodal status, histological grade, ER status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears to be of no prognostic value.

Prognostic value of p53 in breast invasive ductal carcinoma: an immunohistochemical study on 942 cases.

P53 immunohistochemical detection using DO7 antibody on 942 cases of previously untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9 months (89 to 160) was performed. Three hundred and three (32%) tumors were positive. All positive tumors were taken into account, positivity ranging from 1 to 100% of tumoral cells. The Chi square test showed significant negative correlation between p53 positivity and age (p = 0.01), estrogen receptor status (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant positive correlation with tumor grade according to the Scarff, Bloom and Richardson system (SBR Grade) (p < 0.0001). There was no significant association with tumor size or nodal status. Concerning the univariate analysis, in the whole group and node-positive group (n = 544) p53 positivity was highly significant for overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p = 0.0003). In the node-negative group (n = 398), p53 was significant with respect to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent prognostic parameter in the multivariate analysis in the whole group and the node-positive group, though of minor significance compared to axillary lymph node status, SBR grade, progesterone receptor status and tumor size.

[Lymphoid depletion type 4 Hodgkin disease. Anatomoclinical review of 35 cases]. / Maladie de Hodgkin type 4 à déplétion lymphoïde. Révision anatomoclinique de 35 cas.

The pathological material of 35 patients with Hodgkin's disease lymphocyte-depletion type (type 4) is reviewed with an immunohistochemistry study on paraffin-embedded sections. The new pathologic data are compared with clinical features. These 35 patients are 4.7% of 742 previously untreated patients managed in this institution from 1960 to 1991. The diagnosis of 31 of the 35 patients was rectified, 17 to non-Hodgkin's lymphoma (12 unclassifiable and five anaplastic Ki-1 positive) and 14 to another type of Hodgkin's disease (six nodular sclerosis and eight mixed cellularity). In four cases, the pathologic material was neither sufficient nor satisfactory to allow a clear-cut distinction between Hodgkin's disease and non-Hodgkin's lymphoma. The analysis of clinical data before and after pathological revision did not show any difference in clinical features, either between Hodgkin's disease "type 4" and other types (1, 2 or 3) or between cases with Hodgkin's disease and those with non-Hodgkin's lymphoma. There is, however, a significant male predominance for Hodgkin's disease versus non-Hodgkin's lymphoma (P = 0.029, exact Fisher test), and B symptoms in non-Hodgkin's lymphomas (P = 0.056), whereas B symptoms are commonly seen in advanced stages of Hodgkin's disease. It is emphasized that all Hodgkin's disease of lymphocyte-depletion type should be reviewed and discussed before any treatment, and this diagnosis actually means non-Hodgkin's lymphoma or other types of Hodgkin's disease.

Lhermitte-Duclos type cerebellum hamartoma and Cowden disease.

A Lhermitte-Duclos type cerebellum hamartoma is reported in a woman with a diffuse hamartomatous condition involving the breast, thyroid, colon, skin, and kidney. The family history demonstrated the autosomal dominant transmission of this hamartomatous syndrome, and indicated the diagnosis of Cowden disease. This observation supports the recent hypothesis of Lhermitte-Duclos disease associated with Cowden disease as being a single phakomatosis.