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Significance of lymphoplasmocytic infiltration around tumor cell in the prediction of regional lymph node metastases in patients with invasive squamous cell carcinoma of the vulva: A clinicopathologic study
GYNECOLOGIC
ONCOLOGY
3,
200-205 (1989)
Significance of Lymphoplasmocytic Infiltration around Tumor Cell in the Prediction of Regional Lymph Node Metastases in Patients with Invasive Squamous Cell Carcinoma of the Vulva: A ClinicoPathologic Study NADER HUSSEINZADEH,
M.D., *,I TERRENCE WESSELER, M.D.,? HELMUT SCHELLHAS, M.D.,f AND WILLIAM NAHHAS, M.D.§
*Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, tDepartment of Pathology, University of Cincinnati, Cincinnati, Ohio 45267; *Division of Gynecologic Oncology, The Jewish Hospital of Cincinnati; and $Division of Gynecologic Oncology, Miami Valley Hospital, Wright State University, Dayton, Ohio 45431 Received April 27, 1988
Histologic material from 42 patients treated for invasive squamous cell carcinoma of the vulva was studied to determine the prognostic significance of lymphoplasmocytic infiltration around tumor cells in the prediction of regional lymph node metastases. No correlation was found between lymphoplasmocytic infiltration and nodal metastasis with respect to degree of tumor differentiaton, stage of disease, and vascular channel involvement. The presenceor absenceof lymphoplasmocytic infiltration around tumor cells appears to have no prognostic value in predicting nodal metastases. Q 1989 Academic Press, Inc.
had fewer inguinal node metastases and better survival than those without lymphocytic infiltration; the association was not statistically significant. The present study was undertaken to determine the prognostic value of lymphoplasmocytic infiltration around tumor cells in regard to regional node metastases in patients with primary invasive squamous cell carcinoma of the vulva. MATERIALS
AND METHODS
The study group consisted of 42 evaluable patients with Stage I-IV primary invasive squamous cell carciINTRODUCTION noma of the vulva who were treated between 1975 and Size of the primary lesion, histologic grade, stage of 1985. the disease, pattern of invasion, depth of stromal invaAll patients were staged preoperatively according to sion, vascular channel involvement, and nodal metas- International Federation of Gynecology and Obstetrics tases have shown to be prognostically significant in pa- (FIGO) criteria. tients with invasive squamous cell carcinoma of the vulva Thirty-five patients had radical vulvectomy with uni[l-5]. The presence of lymphoplasmocytic infiltration lateral or bilateral inguinal-femoral lymphadenectomy around tumor cells has been shown to be of prognostic and 7 patients had additional unilateral or bilateral pelvic value and associated with increased survival in patients lymphadenectomy. Histopathologic specimens were rewith breast [6], stomach [7-91, colon [lo,1 11, bladder viewed by one of the authors (T.W.). The lymphoplas[12], cervical [13,14,17], and vulvar cancer [3,15]. Gos- mocytic infiltrate at the periphery of any given tumor ling ef al. [15] have shown that the presence of lymphoid was graded in a semiquantitative manner. If there was infiltration is associated with increased survival in pa- no such infiltration, it was considered Grade 0. Those tients with squamous cell carcinoma of the vulva. Boyce tumors with sparse lymphoplasmocytic infiltration were et al. [3] reported that patients with marked lymphocytic graded as 1+ (Fig. 1) and those with very dense infiltrainfiltration in the stroma surrounding the primary tumor tion were graded as 3+ (Fig. 2). If infiltration was intermediate between the two extremes, it was graded as ’ To whom reprint requests should be addressed at University of 2+ (Fig. 3). Inflammatory infiltrates adjacent to foci of Cincinnati Medical Center, Division of Gynecologic Oncology, 231 necrosis were ignored. When there was a significant variability within a tumor in regard to the degree of lymBethesda Avenue, Cincinnati, OH 45267-0526. 200
0090-8258/89 $1.50 Copyright 0 1989by Academic Press,Inc. All rights of reproduction in any form reserved.
LYMPHOPLASMOCYTIC
FIG. 1.
INFILTRATION
AROUND
TUMOR
CELLS
201
Sparse lymphoplasmocytic infiltration (Grade 1’).
phoplasmocytic infiltration, the average density of infiltration was recorded. RESULTS The age range was 30-86 years with a mean age of 66 years. Eight patients had Stage I, 23 had Stage II, 9 had Stage III, and 2 had Stage IV disease. The incidence of nodal metastases correlated directly with stage of disease ranging from 12% for Stage I disease to 100% in patients with Stage IV disease (Table 1). Lymphoplasmocytic infiltration was determined to be absent in two patients (5%). It was l+ in 11 patients (26%), 2+ in 23 patients (48%), and 3+ in 9 patients (21%). The degree of lymphoplasmocytic infiltration, when present, did not appear to give any meaningful correlations in regard to nodal metastases (Table 2). In regard to nodal metastases, no association was found between lymphoplasmocytic infiltration and stage of the disease (Table 3), histologic grade (Table 4), depth of stromal invasion (Table 5), or vascular channel involvement (Table 6).
DISCUSSION Cellular immune competence, as evidenced by lymphoplasmocytic infiltration around tumor cells and morphologic changes in regional lymph nodes, has been reported to correlate with patient prognosis and survival in a number of different tumors. Lymphoid infiltration in and around the tumor and sinus histiocytosis in draining axillary lymph nodes have been shown to be associated with an improved prognosis in patients with carcinoma of the breast [6,7,16]. A similar relationship was also shown in gastric carcinoma. Black et al. [7,8,18] studied the relationship between survival and the structural features such as nuclear differentiation, degree of lymphoid infiltration, and lymphoid structure of the regional lymph node. They confirmed that prolonged survival in patients with gastric cancer was associated with an increased incidence of lymphoid infiltration, follicular hyperplasia in the regional lymph node, and greater nuclear differentiation. Tabuchi et al. [9], using a stathmokinetic technique to
202
HUSSEINZADEH
ET AL.
FIG. 2. Dense lymphoplasmocytic infiltration (Grade 3’).
analyze the mitotic activity of human gastric cancer, noted that moderate and marked degrees of infiltration suppress the mitotic activity of cancer cells and were more frequent in patients with early stage and well-differentiated cancer. In patients with colon cancer, factors that appeared to correlate best with patient survival were the stage of the disease, grade of tumor, and the number of involved nodes. Murray et al. [ 101and Nacopoulos [ 111reported 78% and 53% 5-year survival when lymphoplasmocytic infiltrations were present. In contrast, when lymphoplasmocytic reactions were absent, 5-year survival was 40% and 30%, respectively. They also noted improved survival with some histologic patterns in regional lymph nodes such as sinus histiocytosis [lo] and lymphocyte predominance [I 11. A similar observation was noted in patients with transitional cell carcinoma of the bladder
[121. In cervical cancer the importance of host-immune response has been suggested by some investigators [19,20]. VanNagell [ 13,141 reported that lymphoplasmocytic infiltration was not associated with cell type and lymph
node morphology in patients with invasive cervical cancer but was associated with a significant decrease in the incidence of lymph node metastases. Nine percent of patients with marked lymphocytic response had metastatic disease in pelvic nodes as compared to 25% nodal metastases in patients with minimal lymphocytic infiltration. Likewise, the incidence of recurrence was reduced from 34% to 7% in the presence of a marked lymphoplasmocytic tumor infiltrate. Ninety-five percent of those with marked lymphoid reaction survived 2-15 years following therapy whereas 31% with minimal or no lymphoplasmocytic response died of recurrent disease during this period. Gusberg et al. [I71 reported an inverse relationship between the presence of stromal response and absence of positive lymph nodes in patients with invasive cervical cancer. Of the patients with good lymphocytic response, 13.8% had positive node compared to those with poor lymphocytic response who had 66.6% nodal metastases. In patients with squamous cell carcinoma of the vulva, Gosling et al. [15] have shown a lower 5-year survival for patients whose tumor had none to minimal infiltration
LYMPHOPLASMOCYTIC
INFILTRATION
AROUND TUMOR CELLS
203
PIG. 3. Intermediate lymphoplasmocytic infiltration (Grade 2’).
TABLE 1 Stage and Nodal Metastases Stage I II III IV
No. of patients (%)
Node metastases (%)
8 (1%) 23 (55%) 9 (21%) 2 (5%)
1 (12%) 8 (35%) 5 (56%) 2 (100%)
P value”
<.05
’ Fisher exact test.
TABLE 2 Lymphocytic Infiltration and Nodal Metastases L.I.
0 1+ 2’ 3’
No. of patients (%)
Nodal metastases (%)
2 (5%) 11 (26%) 20 (48%) 9 (21%)
0 6 (55%) 7 (35%) 3 (33%)
u Chi-square, x = 2.661 on 3 df.
P value”
P>
.l
compared to those with marked infiltration (34.3 vs 61.9%). Boyce et al. [3] reported that patients with marked lymphocytic infiltration in the stroma surrounding the primary tumor had fewer inguinal node metastases than those without lymphocytic infiltration (37 vs 45%). There was also better 5-year survival in patients with marked lymphocytic infiltration compared to those with mild infiltration (75 vs 63%). However, the association between these parameters was not statistically significant. Our data indicate that the density of lymphoplasmocytic infiltration when present did not correlate with regional node metastases regardless of stage of disease, histologic grade of tumor, depth of tumor invasion, or vascular channel involvement. The presence or absence of lymphoplasmocytic infiltration around tumor cells appeared to have no value as a prognostic factor in predicting nodal metastases in patients with invasive squamous cell carcinoma of the vulva.
204
HUSSEINZADEH
ET AL.
TABLE 3 Lymphocytic Infiltration vs Stage and Nodal Metastases L.I.”
No.
0
2 11 20 9
1’ 2’ 3’
Stage I 1 5 2
+ Node
Stage II
+ Node
Stage III
+ Node
Stage IV
+ Node
0 1 (5%) 0
2 4 13 5
0 1 (9%) 5 (25%) 2 (22%)
4 2 2
3 (27%) 1 (5%) 1 (11%)
2 -
2 (18%) -
a Lymphocytic infiltration.
REFERENCES TABLE 4 Lymphocytic Infiltration vs Histologic Grade and Nodal Metastases L.I.” 0 1’ 2’ 3’
No.
G,
+ Node
G2
+ Node
G,
+ Node
211 20 9
2 7 3
0 3 (15%) 0
2 4 10 4
0 3 (27%) 3 (15%) 2 (22%)
1 5 3 2
0 3 (27%) 1 (5%) 1 (11%)
’ Lymphocytic infiltration.
TABLE 5 Lymphocytic Infiltration vs Stromal Invasion and Nodal Metastases L.I.” 0 1’ 2’ 3’
No.
6 5 mm
+ Node
25
+ Node
2 11 20 9
2 2 9 5
0 1 (9%) 1 (5%) 1 (11%)
-
5 (45%) 6 (30%) 2 (22%)
9 11 4
’ Lymphocytic infiltration.
TABLE 6 Lymphocytic Infiltration vs Vascular Channel Involvement and Nodal Metastases L.I.” 0 1’ 2’ 3’
No.
Absent
+ Node
Present
+ Node
2 11 20 9
1 7 19 9
0 2 (18%) 6 (32%) 3 (33%)
1 4 I -
0 4 (26%) 1 (5%) -
n Lymphocytic infiltration.
1. Franklin, E. W., and Rutledge, P. Prognostic factor in epidermoid carcinoma of the vulva, Obstet. Gynecol. 37, 892-901 (1971). 2. Donaldson, E. S., Powel, D. E., Hanson, M. R., and Van Nagell, J. R. Prognostic parameters in invasive vulvar cancer, Gynecol. Oncol. 11, 190-194 (1981). 3. Boyce, J., Fruchter, R. G., Kasambilides, E., Nicastri, A. D., Sedlis, A., and Remy, J. C. Prognostic factors in carcinoma of the vulva, Gynecol. Oncol. 20, 364-377 (1985). 4. Andreasson, B., and Nyboe, J. Predictive factors with reference to low-risk metastases in squamous cell carcinoma in the vulvar region, Gynecol. Oncol. 21, 196-206 (1985). 5. Husseinzadeh, N., Zaino, R., Nahhas, W. A., and Mortel. R. The significance of histologic findings in predicting nodal metastases in invasive squamous cell carcinoma of the vulva, Gynecol. Oncol. 16, 105-111 (1983). 6. Black, M. M., Kerpe, S., and Speer, F. D. Lymph node structure in patients with cancer of breast, Amer. J. Pathol. 24, 505-521 (1953). 7. Black, M. M., Opler, S. R., and Speer, F. D. Structural representations of tumor-Host relationships in gastric carcinoma, Surg. Gynecol. Obstet. 102, 599-603 (1956). 8. Black, M. M., Freeman, C., Mork, T., Harvei, S., and Culter, S. J. Prognostic significance of microscopic structure of gastric carcinoma and their regional lymph nodes, Cancer 27, 703-711 (1971). 9. Tabuchi, Y., Takiguchi, Y., Murayama, Y., and Saito, Y. Effect of cellular reaction in gastric cancer tissue and in regional lymph nodes on the mitotic activity of cancer cells, Gunn 72,45-52 (1981). 10. Murray, D., Hreno, A., Dutton, J., and Hampson, L. G. Prognosis in colon cancer, a pathologic reassessment, Arch. Surg. 110, 903913 (1975). 11. Nacopoulos, L., Azaris, P., Papacharalampous, N., and Davaris, P. Prognostic significance of histologic host response in cancer of the large bowel, Cancer 47, 930-936 (1981). 12. Marginez-Pineiro, J. A., Gamallo, C., Isoma, S., Matron, C., Ortas, J., and Contreras, F. Significance and prognostic value of morphology of regional lymph nodes and of peritumoral lymphocycle infiltration in bladder cancer, Eur. Ural. 5, 7-13 (1979). 13. Van Nagell, J. R., Donaldson, E. S., Wood, E. G., and Parker, J. The significance of vascular invasion and infiltration in invasive cervical cancer, Cancer 41, 228-234 (1978). 14. Van Nagell, J. R., Donaldson, E. S., Parker, J. C., VanDyle, A. M., and Wood, E. G. The prognostic significance of pelvic lymph node morphology in carcinoma of the uterine cervix, Cancer 39, 2624-2632 (1977).
LYMPHOPLASMOCYTIC
INFILTRATION
15. Gosling, J. R. C., Abell, M. R., Drolette, B. M., and Loughrin, T. D. Infiltrative squamous cell (epidermoidal) carcinoma of vulva, Cancer 14,330-343 (l%l). 16. Anastassiades, O., and Pryce, D. M. Immunological significance of the morphological changes in lymph node draining breast cancer, Bit. J. Cancer 20, 239-249 (1966). 17. Gusberg, S. B., Yannopoulos, K., and Cohen, C. J. Virulence indices and lymph nodes in cancer of the cervix, Amer. J. Roentgenol. 2, 273-277 (1971).
AROUND TUMOR CELLS
205
18. Black, M. M., and Speer, F. D. Sinus histiocytosis of lymph nodes in cancer, Surg. Gynecol. Obstet. 106, 163-175 (1958). 19. Goldstein, M. S., Shore, B., and Gusberg, S. B. Cellular immunity as a host response to squamous cell carcinoma of the cervix, Amer. J. Obstet. Gynecol. 111, 7X-755 (1971). 20. Chiang, W. T., Wei, P. Y., and Alexander, E. R. Circulatory and cellular immune responses to squamous cell carcinoma of the uterine cervix, Amer. J. Obstet. Gynecol. 126, 116-121 (1976).
ONCOLOGY
3,
200-205 (1989)
Significance of Lymphoplasmocytic Infiltration around Tumor Cell in the Prediction of Regional Lymph Node Metastases in Patients with Invasive Squamous Cell Carcinoma of the Vulva: A ClinicoPathologic Study NADER HUSSEINZADEH,
M.D., *,I TERRENCE WESSELER, M.D.,? HELMUT SCHELLHAS, M.D.,f AND WILLIAM NAHHAS, M.D.§
*Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, tDepartment of Pathology, University of Cincinnati, Cincinnati, Ohio 45267; *Division of Gynecologic Oncology, The Jewish Hospital of Cincinnati; and $Division of Gynecologic Oncology, Miami Valley Hospital, Wright State University, Dayton, Ohio 45431 Received April 27, 1988
Histologic material from 42 patients treated for invasive squamous cell carcinoma of the vulva was studied to determine the prognostic significance of lymphoplasmocytic infiltration around tumor cells in the prediction of regional lymph node metastases. No correlation was found between lymphoplasmocytic infiltration and nodal metastasis with respect to degree of tumor differentiaton, stage of disease, and vascular channel involvement. The presenceor absenceof lymphoplasmocytic infiltration around tumor cells appears to have no prognostic value in predicting nodal metastases. Q 1989 Academic Press, Inc.
had fewer inguinal node metastases and better survival than those without lymphocytic infiltration; the association was not statistically significant. The present study was undertaken to determine the prognostic value of lymphoplasmocytic infiltration around tumor cells in regard to regional node metastases in patients with primary invasive squamous cell carcinoma of the vulva. MATERIALS
AND METHODS
The study group consisted of 42 evaluable patients with Stage I-IV primary invasive squamous cell carciINTRODUCTION noma of the vulva who were treated between 1975 and Size of the primary lesion, histologic grade, stage of 1985. the disease, pattern of invasion, depth of stromal invaAll patients were staged preoperatively according to sion, vascular channel involvement, and nodal metas- International Federation of Gynecology and Obstetrics tases have shown to be prognostically significant in pa- (FIGO) criteria. tients with invasive squamous cell carcinoma of the vulva Thirty-five patients had radical vulvectomy with uni[l-5]. The presence of lymphoplasmocytic infiltration lateral or bilateral inguinal-femoral lymphadenectomy around tumor cells has been shown to be of prognostic and 7 patients had additional unilateral or bilateral pelvic value and associated with increased survival in patients lymphadenectomy. Histopathologic specimens were rewith breast [6], stomach [7-91, colon [lo,1 11, bladder viewed by one of the authors (T.W.). The lymphoplas[12], cervical [13,14,17], and vulvar cancer [3,15]. Gos- mocytic infiltrate at the periphery of any given tumor ling ef al. [15] have shown that the presence of lymphoid was graded in a semiquantitative manner. If there was infiltration is associated with increased survival in pa- no such infiltration, it was considered Grade 0. Those tients with squamous cell carcinoma of the vulva. Boyce tumors with sparse lymphoplasmocytic infiltration were et al. [3] reported that patients with marked lymphocytic graded as 1+ (Fig. 1) and those with very dense infiltrainfiltration in the stroma surrounding the primary tumor tion were graded as 3+ (Fig. 2). If infiltration was intermediate between the two extremes, it was graded as ’ To whom reprint requests should be addressed at University of 2+ (Fig. 3). Inflammatory infiltrates adjacent to foci of Cincinnati Medical Center, Division of Gynecologic Oncology, 231 necrosis were ignored. When there was a significant variability within a tumor in regard to the degree of lymBethesda Avenue, Cincinnati, OH 45267-0526. 200
0090-8258/89 $1.50 Copyright 0 1989by Academic Press,Inc. All rights of reproduction in any form reserved.
LYMPHOPLASMOCYTIC
FIG. 1.
INFILTRATION
AROUND
TUMOR
CELLS
201
Sparse lymphoplasmocytic infiltration (Grade 1’).
phoplasmocytic infiltration, the average density of infiltration was recorded. RESULTS The age range was 30-86 years with a mean age of 66 years. Eight patients had Stage I, 23 had Stage II, 9 had Stage III, and 2 had Stage IV disease. The incidence of nodal metastases correlated directly with stage of disease ranging from 12% for Stage I disease to 100% in patients with Stage IV disease (Table 1). Lymphoplasmocytic infiltration was determined to be absent in two patients (5%). It was l+ in 11 patients (26%), 2+ in 23 patients (48%), and 3+ in 9 patients (21%). The degree of lymphoplasmocytic infiltration, when present, did not appear to give any meaningful correlations in regard to nodal metastases (Table 2). In regard to nodal metastases, no association was found between lymphoplasmocytic infiltration and stage of the disease (Table 3), histologic grade (Table 4), depth of stromal invasion (Table 5), or vascular channel involvement (Table 6).
DISCUSSION Cellular immune competence, as evidenced by lymphoplasmocytic infiltration around tumor cells and morphologic changes in regional lymph nodes, has been reported to correlate with patient prognosis and survival in a number of different tumors. Lymphoid infiltration in and around the tumor and sinus histiocytosis in draining axillary lymph nodes have been shown to be associated with an improved prognosis in patients with carcinoma of the breast [6,7,16]. A similar relationship was also shown in gastric carcinoma. Black et al. [7,8,18] studied the relationship between survival and the structural features such as nuclear differentiation, degree of lymphoid infiltration, and lymphoid structure of the regional lymph node. They confirmed that prolonged survival in patients with gastric cancer was associated with an increased incidence of lymphoid infiltration, follicular hyperplasia in the regional lymph node, and greater nuclear differentiation. Tabuchi et al. [9], using a stathmokinetic technique to
202
HUSSEINZADEH
ET AL.
FIG. 2. Dense lymphoplasmocytic infiltration (Grade 3’).
analyze the mitotic activity of human gastric cancer, noted that moderate and marked degrees of infiltration suppress the mitotic activity of cancer cells and were more frequent in patients with early stage and well-differentiated cancer. In patients with colon cancer, factors that appeared to correlate best with patient survival were the stage of the disease, grade of tumor, and the number of involved nodes. Murray et al. [ 101and Nacopoulos [ 111reported 78% and 53% 5-year survival when lymphoplasmocytic infiltrations were present. In contrast, when lymphoplasmocytic reactions were absent, 5-year survival was 40% and 30%, respectively. They also noted improved survival with some histologic patterns in regional lymph nodes such as sinus histiocytosis [lo] and lymphocyte predominance [I 11. A similar observation was noted in patients with transitional cell carcinoma of the bladder
[121. In cervical cancer the importance of host-immune response has been suggested by some investigators [19,20]. VanNagell [ 13,141 reported that lymphoplasmocytic infiltration was not associated with cell type and lymph
node morphology in patients with invasive cervical cancer but was associated with a significant decrease in the incidence of lymph node metastases. Nine percent of patients with marked lymphocytic response had metastatic disease in pelvic nodes as compared to 25% nodal metastases in patients with minimal lymphocytic infiltration. Likewise, the incidence of recurrence was reduced from 34% to 7% in the presence of a marked lymphoplasmocytic tumor infiltrate. Ninety-five percent of those with marked lymphoid reaction survived 2-15 years following therapy whereas 31% with minimal or no lymphoplasmocytic response died of recurrent disease during this period. Gusberg et al. [I71 reported an inverse relationship between the presence of stromal response and absence of positive lymph nodes in patients with invasive cervical cancer. Of the patients with good lymphocytic response, 13.8% had positive node compared to those with poor lymphocytic response who had 66.6% nodal metastases. In patients with squamous cell carcinoma of the vulva, Gosling et al. [15] have shown a lower 5-year survival for patients whose tumor had none to minimal infiltration
LYMPHOPLASMOCYTIC
INFILTRATION
AROUND TUMOR CELLS
203
PIG. 3. Intermediate lymphoplasmocytic infiltration (Grade 2’).
TABLE 1 Stage and Nodal Metastases Stage I II III IV
No. of patients (%)
Node metastases (%)
8 (1%) 23 (55%) 9 (21%) 2 (5%)
1 (12%) 8 (35%) 5 (56%) 2 (100%)
P value”
<.05
’ Fisher exact test.
TABLE 2 Lymphocytic Infiltration and Nodal Metastases L.I.
0 1+ 2’ 3’
No. of patients (%)
Nodal metastases (%)
2 (5%) 11 (26%) 20 (48%) 9 (21%)
0 6 (55%) 7 (35%) 3 (33%)
u Chi-square, x = 2.661 on 3 df.
P value”
P>
.l
compared to those with marked infiltration (34.3 vs 61.9%). Boyce et al. [3] reported that patients with marked lymphocytic infiltration in the stroma surrounding the primary tumor had fewer inguinal node metastases than those without lymphocytic infiltration (37 vs 45%). There was also better 5-year survival in patients with marked lymphocytic infiltration compared to those with mild infiltration (75 vs 63%). However, the association between these parameters was not statistically significant. Our data indicate that the density of lymphoplasmocytic infiltration when present did not correlate with regional node metastases regardless of stage of disease, histologic grade of tumor, depth of tumor invasion, or vascular channel involvement. The presence or absence of lymphoplasmocytic infiltration around tumor cells appeared to have no value as a prognostic factor in predicting nodal metastases in patients with invasive squamous cell carcinoma of the vulva.
204
HUSSEINZADEH
ET AL.
TABLE 3 Lymphocytic Infiltration vs Stage and Nodal Metastases L.I.”
No.
0
2 11 20 9
1’ 2’ 3’
Stage I 1 5 2
+ Node
Stage II
+ Node
Stage III
+ Node
Stage IV
+ Node
0 1 (5%) 0
2 4 13 5
0 1 (9%) 5 (25%) 2 (22%)
4 2 2
3 (27%) 1 (5%) 1 (11%)
2 -
2 (18%) -
a Lymphocytic infiltration.
REFERENCES TABLE 4 Lymphocytic Infiltration vs Histologic Grade and Nodal Metastases L.I.” 0 1’ 2’ 3’
No.
G,
+ Node
G2
+ Node
G,
+ Node
211 20 9
2 7 3
0 3 (15%) 0
2 4 10 4
0 3 (27%) 3 (15%) 2 (22%)
1 5 3 2
0 3 (27%) 1 (5%) 1 (11%)
’ Lymphocytic infiltration.
TABLE 5 Lymphocytic Infiltration vs Stromal Invasion and Nodal Metastases L.I.” 0 1’ 2’ 3’
No.
6 5 mm
+ Node
25
+ Node
2 11 20 9
2 2 9 5
0 1 (9%) 1 (5%) 1 (11%)
-
5 (45%) 6 (30%) 2 (22%)
9 11 4
’ Lymphocytic infiltration.
TABLE 6 Lymphocytic Infiltration vs Vascular Channel Involvement and Nodal Metastases L.I.” 0 1’ 2’ 3’
No.
Absent
+ Node
Present
+ Node
2 11 20 9
1 7 19 9
0 2 (18%) 6 (32%) 3 (33%)
1 4 I -
0 4 (26%) 1 (5%) -
n Lymphocytic infiltration.
1. Franklin, E. W., and Rutledge, P. Prognostic factor in epidermoid carcinoma of the vulva, Obstet. Gynecol. 37, 892-901 (1971). 2. Donaldson, E. S., Powel, D. E., Hanson, M. R., and Van Nagell, J. R. Prognostic parameters in invasive vulvar cancer, Gynecol. Oncol. 11, 190-194 (1981). 3. Boyce, J., Fruchter, R. G., Kasambilides, E., Nicastri, A. D., Sedlis, A., and Remy, J. C. Prognostic factors in carcinoma of the vulva, Gynecol. Oncol. 20, 364-377 (1985). 4. Andreasson, B., and Nyboe, J. Predictive factors with reference to low-risk metastases in squamous cell carcinoma in the vulvar region, Gynecol. Oncol. 21, 196-206 (1985). 5. Husseinzadeh, N., Zaino, R., Nahhas, W. A., and Mortel. R. The significance of histologic findings in predicting nodal metastases in invasive squamous cell carcinoma of the vulva, Gynecol. Oncol. 16, 105-111 (1983). 6. Black, M. M., Kerpe, S., and Speer, F. D. Lymph node structure in patients with cancer of breast, Amer. J. Pathol. 24, 505-521 (1953). 7. Black, M. M., Opler, S. R., and Speer, F. D. Structural representations of tumor-Host relationships in gastric carcinoma, Surg. Gynecol. Obstet. 102, 599-603 (1956). 8. Black, M. M., Freeman, C., Mork, T., Harvei, S., and Culter, S. J. Prognostic significance of microscopic structure of gastric carcinoma and their regional lymph nodes, Cancer 27, 703-711 (1971). 9. Tabuchi, Y., Takiguchi, Y., Murayama, Y., and Saito, Y. Effect of cellular reaction in gastric cancer tissue and in regional lymph nodes on the mitotic activity of cancer cells, Gunn 72,45-52 (1981). 10. Murray, D., Hreno, A., Dutton, J., and Hampson, L. G. Prognosis in colon cancer, a pathologic reassessment, Arch. Surg. 110, 903913 (1975). 11. Nacopoulos, L., Azaris, P., Papacharalampous, N., and Davaris, P. Prognostic significance of histologic host response in cancer of the large bowel, Cancer 47, 930-936 (1981). 12. Marginez-Pineiro, J. A., Gamallo, C., Isoma, S., Matron, C., Ortas, J., and Contreras, F. Significance and prognostic value of morphology of regional lymph nodes and of peritumoral lymphocycle infiltration in bladder cancer, Eur. Ural. 5, 7-13 (1979). 13. Van Nagell, J. R., Donaldson, E. S., Wood, E. G., and Parker, J. The significance of vascular invasion and infiltration in invasive cervical cancer, Cancer 41, 228-234 (1978). 14. Van Nagell, J. R., Donaldson, E. S., Parker, J. C., VanDyle, A. M., and Wood, E. G. The prognostic significance of pelvic lymph node morphology in carcinoma of the uterine cervix, Cancer 39, 2624-2632 (1977).
LYMPHOPLASMOCYTIC
INFILTRATION
15. Gosling, J. R. C., Abell, M. R., Drolette, B. M., and Loughrin, T. D. Infiltrative squamous cell (epidermoidal) carcinoma of vulva, Cancer 14,330-343 (l%l). 16. Anastassiades, O., and Pryce, D. M. Immunological significance of the morphological changes in lymph node draining breast cancer, Bit. J. Cancer 20, 239-249 (1966). 17. Gusberg, S. B., Yannopoulos, K., and Cohen, C. J. Virulence indices and lymph nodes in cancer of the cervix, Amer. J. Roentgenol. 2, 273-277 (1971).
AROUND TUMOR CELLS
205
18. Black, M. M., and Speer, F. D. Sinus histiocytosis of lymph nodes in cancer, Surg. Gynecol. Obstet. 106, 163-175 (1958). 19. Goldstein, M. S., Shore, B., and Gusberg, S. B. Cellular immunity as a host response to squamous cell carcinoma of the cervix, Amer. J. Obstet. Gynecol. 111, 7X-755 (1971). 20. Chiang, W. T., Wei, P. Y., and Alexander, E. R. Circulatory and cellular immune responses to squamous cell carcinoma of the uterine cervix, Amer. J. Obstet. Gynecol. 126, 116-121 (1976).