LYMPHOMAS NOT HODGKINIENS PRIMITIVES OF TESTICULAR CANCER: LONG-TERM PROGNOSIS ASSOCIATED WITH TREATMENT COMBINING CHEMOTHERAPY SYSTEMIC AND INTRATHECAL
Home no primitive hodgkiniens of testicular lymphoma: long-term prognosis associated with treatment combining systemic chemotherapy and intrathecal
RETOUR27 MARCH 2009
Keywords: primitive LMNH, testicular Lymphoma authors: C. Seneschal, F. St., T. little, J. small Reference: Prog 2009, 19, 3, 209-214, Urol download this form in format PDF objectives: assess the long term of a retrospective series of lymphoma prognosis No Hodgkiniens (LMNH) primitive testicular malignant treated by orchiectomy and systemic adjuvant chemotherapy and intrathecal.
Patients and methods: from 1992 to 2006, eight consecutive patients have been supported for a primitive LMNH of testicular cancer (stages: AI [n = 1], IEA [n = 5], [n = 1] IIEA, IVEA [n = 1]) and retrospectively analyzed. All of these tumors were high-grade malignancy. The average age of patients at diagnosis was 64 years (46-78). All of these patients received an extended orchiectomy and received a combined treatment of systemic chemotherapy and intrathecal CHOP or VACP type. Six patients received radiotherapy closing regional and three brain radiation.
Results: The mean follow-up was 90.5 months (months 12-168). Five patients (62.5%) presented a complete response, a patient a brain relapse controlled by a second course of chemotherapy. Three patients died, one of a septic shock during chemotherapy (IVEA stage), another of mesenteric infarction (stage IAE) and the latest in acute coronary thrombosis while he was in remission full.
Conclusion: Despite a reputed prognosis, the primitive LMNH of testicular cancer treated with adjuvant systemic chemotherapy and intrathecal seem to associated with a good specific long-term survival. Unfortunately, chemotherapy-related mortality is not negligible (close to 12.5% in our series) and does not seem to fully protect the brain recurrence.
INTRODUCTION
Primitive no Hodgkiniens (LMNH) malignant lymphomas of the testis are rare, they represent between 1 and 9% of testicular tumors. They are particularly common in older men (average age of diagnosis: 60) [2,3]. The most common histological is type B (developed from peripheral B cells), diffuse and large cell according to the 2001 who classification. These lymphomas are characterized by a poor prognosis.
Through retrospective analysis of a monocentric series old LMNH testicular primitive treated by orchiectomy and chemotherapy adjuvant (systemic and intrathecal), we remind the therapeutic principles and evolution long term of these tumors, without validating the unfavourable evolution.
PATIENTS AND METHODS
We retrospectively analyzed records of eight consecutive patients followed for a primitive LMNH of testicular cancer. These patients were diagnosed and treated between 1992 and 2004. Initial diagnostic support has involved a complete general examination, a complete blood count, an electrophoresis of serum proteins, the measure of the rate of LDH, a standard x-ray of the chest, sinuses and the cavum, a thoracic scanner and abdominopelvien and a biopsy of the spinal cord. Transthoracic echocardiography, an oesogastro-duodenal fibroscopy and a lumbar puncture occurred when there was a symptomatology that evoke an impairment of the corresponding explored bodies.
A bipedieuse lymphography was conducted when ganglion masses were difficult to analyse precisely to the scanner. The stage was defined according to the classification of Ann Arbor (). The histopathological type, immunologic, cytogenetic and molecular has been established according to the classification Revised European - American Classification of Lymphoid Neoplasms (R.E.A.L) defined by the International Lymphoma Study Group, then under the new 2001 who classification. The diagnosis was made in all cases on the part of orchiectomy.
Table 1: Classification of Ann Arbor.
Stage of the classification Definition of stage
I reached a ganglionic territory
II. achievement of several ganglion territories on one side of the diaphragm
III. infringement of several ganglion territories on both sides of the diaphragm
E added, if necessary, at stages I, II or III location by contact of one ganglion with neighbourhood bodies extranodal
Different from the scattered character of stage IV
IV. infringement of one or more organs
Differs from a breach by contact of a ganglion to the organs of neighborhood
General signs
Any of the signs below
B at least one of the signs below
Unexplained weight loss greater than or equal to 10% of the weight of the body in the previous six months
Fever unexplained > 38 ° c in less than 7 days
Profuse night sweats
The spleen is considered to be a ganglion.
The anatomical distribution of ganglion Territories achieved varies according to the stage.
An extended unilateral orchidectomy inguinal through was conducted for seven patients and bilateral to one-eighth (of a prostatic adenocarcinoma treatment). In all cases, the patients received chemotherapy intrathecally at base of methotrexate and corticosteroids. This chemotherapy was associated in the first intention with a multidrug systemic type CHOP (Protocol of reference of the aggressive LMNH including cyclophosphamide, Adriamycin, vincristine, and prednisone) three cures 21 days apart (4 (case), a VAD protocol more CHVP (1 case), VACP (2 cases) and a CHOP protocol more MABTHERA (1 case).
Treatment was completed by radiation lomboaortique and ilio-obturator bilateral (in 'Y' reversed) closing for six of the eight patients. It was completed for a patient by a splenic, Mediastinal irradiation and sus-clavicular, for another by scrotal exposure and sus-clavicular. Finally, a prophylactic Brain radiotherapy was conducted for three patients. A patient received a stem cell autograft of beginning, at the end of the three cures chemotherapy. Monitoring was based on clinical examination, the blood work, blood electrolytes, serum LDH dosage every three months and an annual best-abdominopelvien scanner. A patient (M.D.) showed relapse treated by a protocol of intensive combination chemotherapy of catch-up, complemented by a brain radiotherapy and an autologous transplant of stem cells.
At the date of the latest (2007), patients were considered:
living in complete remission (HRV);
living with progressive tumour (ETV);
deceased of their tumor, another disease or complications of treatment (DCD).
RESULTS
The average age when support was 64 years (46-78 years). The average follow-up was 90.5 months (months 12-168). The circumstance of the most common discovery was a unique and isolated testicular swelling (7 out of 8 cases). One of the patients had bilateral swelling (C.M.). Most of patients (7 out of 8 cases) showed a preserved condition. Three patients were carriers of one or several locations ganglion retroperitoneales associated with testicular location: iliac, lomboaortique, Mediastinal and sus-clavicular left. A patient (D.B.) was an invasion of the osteomedullaire (BOM) biopsy and myocardial infiltration of origin polyposis. Among the testicular markers: β - HCG and α-foetoproteine were always normal, the LDH were high in both cases in eight. Pathological examination concluded that the presence of a high malignancy for patients eight NHL: immunoblastique and centroblastique (n = 1), diffuse large polymorphic cell (n = 3), immunoblastique and plasmocytoide (n = 1) and diffuse large cell centroblastiques centrocytiques (n = 1). The other two patients were carriers of a diffuse large cell NHL () of cytological type not specified. The immunological phenotype was B in any case ().
Figure 1: Infiltration of the testicle by a proliferation in large cells around a water tube seminiferous still analyzable (HES × 200).
Figure 2: Study Immunohistochemistry confirming the diagnosis of lymphoma B with a positivity of tumor cells for the CD20 (IHC × 200).
Of these eight patients, none died of his tumor. Five are still alive, one died of complications in connection with her chemotherapy (septic shock), the second died of mesenteric infarction while he was in complete remission and the last died of acute coronary thrombosis While he was in complete remission (). A patient (M.D.) showed a brain relapse to 15 months of the end of the treatment.
Table 2: Characteristics of patients.
Patient Age (years) review pathological examination clinic extension treatment follow-up assessment (months) status
P.M. 78 LMNH high-grade type B stage IV, immunoblastique centroblastique increase volume left testicle and AEG + Orchiectomy expanded more 8 chemo alternating VAD more CHVP more 12 DCD intrathecal injection
Septic shock
G.C. 69 LMNH high grade type B stage IAE immunoblastique and plasmocytoide right testicular pain − Orchiectomy expanded more 3 chemo CHOP more intrathecal injection more radiotherapy closing local 132 HRV
H.R. 70 LMNH large cells type B stage I0AE increase volume right testicle − Orchiectomy expanded more 3 chemo CHOP more intrathecal injection more radiotherapy regional and fence cerebral 168 HRV
J.B. 58 LMNH diffuse large cell polymorphs type B stage EBCI increase volume left testicle + Orchiectomy expanded more 3 chemo VACP more intrathecal injection more radiotherapy regional and fence cerebral 156 DCD
Myocardial infarction
G.D. 59 LMNH high-grade, diffuse large cell centrocytiques polymorphs type B stage IAE increase volume right testicle − Orchiectomy expanded more 3 chemo CHOP more intrathecal injection more radiotherapy closing local 16 DCD
Mesenteric infarction
D.B. 46 LMNH, type B, large stage IAE increase volume right testicle cell + (BOM +) Orchiectomy expanded 4 chemo MABTHERA and CHOP more intrathecal injection more 48 HRV stem cells autograft
M.C. 77 LMNH type B large cell stage the increase volume left and right testicle − Orchiectomy polymorphs expanded more 3 chemo CHOP more intrathecal injection more radiotherapy closing regional 72 HRV
M.D. 52 LMNH, diffuse large cell centroblastiques centrocytiques type B stage the increase volume right testicle − bilateral Orchiectomy extended plus 3 chemo VACP more intrathecal injection more radiotherapy closing local relapse treated by cerebral radiotherapy more 120 HRV stem cells autograft
HRV: complete living remission; DCD: d., whatever the cause.
DISCUSSION
This observational, driving series on 14 years, reflects the scarcity of the NHL to testicular initial clinical presentation, with a total of eight comments. However, this clinical scarcity is not closer to the pathological rarity, since the frequency of these tumors would be close to 19% in some series of published autopsies. The age of diagnosis is typically over 50 years, what shows our analysis with 87.5% of patients beyond this age group [1,2,3–9]. Most testicular tumor forms of NHL are located (13-50%) [2-5]. Our series is in agreement with this because seven out of eight cases are considered as having stages IE or second from Ann Arbor. However, these figures are related to completeness of follow-up examinations. Currently, the MTR extension includes systematically by best-abdominopelvien scanner imagery. Depending on the clinic, imaging of the central nervous system may be practiced. In this case, the MRI seems more contributory. It will be associated with a lumbar puncture. Most recent histopathology studies referring to the working formulation for clinical use are a majority (50-80%) of NHL diffuse large cell [11,12]. Our series reaffirms the frequency of this form (62.5%), as well as the high grade (100%). The B immunophenotype is most often observed, like most of the other LMNH to extranodal presentation (off cutaneous lymphomas) [9-12].
The prognosis is pejorative because they are aggressive, but potentially curable Lymphoma with current chemotherapy. The oldest series make a low rate of survival to five years with a median of specific survival between 30 and 56 months according to the authors [5-13]. Similarly, the NHL to testicular location is considered at high risk of recurrence, including brain. In addition, relapse is considered as early with a rate of 50% at two years for Zucca and al. . Our series do not find this very bad prognosis of initial tumors (6 patients on 8 living to 48 months) or even that early relapse. On the other hand, the central nervous system actually seems to be a site of privileged relapse (a case of cerebral relapse, in complete remission after six years after second line chemotherapy, Brain radiotherapy and [] stem cell autograft MD]).
Outside their critical condition, these tumors are characterized by the risk of dissemination cerebromeningee, which is five times higher in the NHL diffuse large cell. This risk to talking prevention by [2-15] intrathecal chemotherapy. This option is widely used, but is unfortunately not yet standardized in view of the scarcity of this pathology.
It remains, however, recognized that an orchiectomy is the initial treatment of this condition and that it must be associated with a combination chemotherapy in modern treatment protocols anti-mitotic CHOP type, especially for IE and second stages (high rates of) early relapses). A few teams evoke interest to associate brain and testicular radiation contralateral prophylactic so as to further reduce the risk of relapse.
A special form of NHL to testicular presentation seems to have been isolated in young subjects. It includes most often forms aggressive with predominance of type lymphoblastic or Burkitt or diffuse large cell [16,17]. This population is frequently immediately disseminated and only intensive polychimiotherapies (LAL protocols types) with a strong addition prophylaxis can expect a cure.
Our series found a similar result, since it was the only case of relapse among our eight patients at the level of the central nervous system, to diffuse Lymphoma large cell diagnosed before age 50, despite prophylaxis intrathecally. However, it is important to remember that the series referring to this are purely Pediatric. The extension to adults should be cautious.
CONCLUSION
The primitive NHL of the testicle are about more of 60 tumours, most often to normal testicular markers. In all cases, the supported surgical orchiectomy extended remains the priority. However, the multidisciplinary care is essential for quick and sustainable complete remission. Despite a reputed prognosis, the primitive NHL of testicular cancer treated with adjuvant systemic chemotherapy and intrathecal seem to associated with a good specific long-term survival. Unfortunately, chemotherapy-related mortality is not negligible (1 case in 8 in our series), chemotherapy, which does not seem to fully protect the brain recurrence or contralateral testicular. This risk should discuss the integration of brain and contralateral testicular irradiation prophylactic Protocol classic adjuvant to an orchiectomy in order to decrease the relapse rate and extend the duration of remission.
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