Virchows Arch (2014) 465:697–701 DOI 10.1007/s00428-014-1663-x
ORIGINAL ARTICLE
Primary tumor size predicts pathologic findings in the retroperitoneal lymph nodes in patients with paratesticular rhabdomyosarcoma Shaheen Alanee & Bradley Holland & Danuta Dynda & Onsi Kamel & Sabha Ganai
Received: 3 August 2014 / Revised: 14 September 2014 / Accepted: 29 September 2014 / Published online: 8 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract To determine patient and tumor characteristics that could predict pathologic findings after retroperitoneal lymph node dissection (RPLND) in paratesticular rhabdomyosarcoma (PTRMS), a total of 266 cases of PTRMS diagnosed between 1973 and 2010 were identified from a national database. RPLND dissection was performed in 67 patients, with a mean age of 14.9 years and median survival of 80 months. PTRMS occurred more often on the right side, had embryonal histology, and had an average size of 6.7 cm. Retroperitoneal lymph node (RPLN) metastasis occurred in 40 % (n=27) of patients. Tumor size and age were strong predictors of finding rhabdomyosarcoma in the retroperitoneal lymph nodes when examined by pathologists. Primary tumors larger than 7 cm in size developing in males 12 years or older had four times more odds of being associated with positive findings on pathologic examinations of the retroperitoneal lymph nodes. Patient race, histology, and tumor laterality were not significant predictors of PTRMS metastasis to the RPLN basin. Patients 12 years or older with PTRMS larger than 7 cm have a significant risk of retroperitoneal lymph nodes involvement with PTRMS. Detailed pathologic examination of the lymph nodes in these patients is recommended.
S. Alanee (*) : B. Holland : S. Ganai Department of Surgery, Division of Urology and Division of Surgical Oncology, Southern Illinois University School of Medicine, PO Box 19665, Springfield, IL 62794-9665, USA e-mail: [email protected] D. Dynda Center for Clinical Research, Southern Illinois University School of Medicine, PO Box 19665, Springfield, IL 62794-9665, USA O. Kamel Department of Pathology, Southern Illinois University School of Medicine, PO Box 19665, Springfield, IL 62794-9665, USA
Keywords Paratesticular neoplasm . Primary tumor size . Retroperitoneal lymph node . Rhabdomyosarcoma . SEER database
Introduction We recently examined a male patient in his second decade of life who presented with a right scrotal mass that rapidly increased in size over 6 months. Ultrasound of the scrotum demonstrated a 6.5×3.5×5.2 cm mass that involved the epididymis and was distinct from the testis (Fig. 1). Tumor markers (β-human choriogonadotropin, alpha fetoprotein, and lactic dehydrogenase) were normal and computerized tomography (CT) of the chest, abdomen, and pelvis did not show any signs of metastasis. Considering the rapid tumor growth, orchiectomy was advised and performed promptly. Pathologic examination of the mass revealed poorlydifferentiated paratesticular rhabdomyosarcoma (PTRMS; Fig. 2). After multidisciplinary discussion with concern for the patient’s age of presentation, positron emission tomography (PET) was recommended for further staging. While PET/ CT was negative for macroscopic metastatic disease, the patient was advised to have retroperitoneal lymph node dissection (RPLND) based on evidence showing microscopic pathologic nodal involvement in 17 % of patients without radiographic evidence of disease [3, 17]. Final pathologic examination of the retroperitoneal lymph nodes (LN) did indeed show the presence of rhabdomyosarcoma in those lymph nodes (Fig. 3) in spite of the negative imaging studies performed prior to surgery. PTRMS is the most common primary tumor of the mesenchymal-supporting tissue of the testes in males diagnosed under 36 years of age, with a mean age of 10 years [9, 12, 13]. The treatment of this disease is primarily based on chemotherapy, and controversy persists regarding the
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Virchows Arch (2014) 465:697–701
Fig. 1 Ultrasound of the right testicle. a Transverse view of superior testis showing uninvolved epididymis. b Transverse view of inferior testis demonstrating paratesticular rhabdomyosarcoma (tumor indicated with white arrow)
diagnostic and therapeutic role of RPLND. CT scan has been suggested to predict retroperitoneal LN metastasis in PTRMS as an adequate substitute for pathologic examination of LN removed with RPLND, but multiple studies have documented imaging to miss cases of LN involvement, leading to increased local recurrence [16]. Therefore, it is important to better understand the relationship between patient and disease factors and the incidence of positive pathologic findings in the retroperitoneal LN. Tumor size has previously been shown to be associated with LN metastasis in other malignancies [11, 18], but the relationship between size and metastasis has not been investigated in PTRMS despite the fact that tumor size can be easily appreciated by clinical or radiologic examination. In this study, we focused on effect of primary tumor size and other tumor and patient factors on the incidence of pathologically documented LN metastasis in patients with PTRMS. Recognizing the low incidence of PTRMS, a large national database was used to perform our analysis.
Methods
purpose of this analysis [9]. SEER is a population-based cancer registry that routinely collects high-quality patient data from 17 registries in 14 states and represents an estimated 28 % of the US population. The SEER database was queried, after institutional review board determination, for the diagnosis of PTRMS from 1973 to 2010 using SEER*Stat software version 8.1.2 [10]. PTRMS cases were identified using the third edition of the International Classification of Diseases for Oncology (IDC-O-3) codes 8900 to 8904, 8910, 8912, 8920 to 8921, and 8991 and primary anatomical site codes of C62.0, C62.1, C62.9, C63.0, C63.1, and C63.2, which respectively code for undescended testis, descended testis, testis, epididymis, spermatic cord, and scrotum. Typically, SEER obtains histological confirmation of more than 90 % of all cancers. SEER requires reviewing all pathology reports to complete cancer reporting. If the pathology department is computerized and each report contains an ICD-O histology and behavior code, a computerized list of diagnoses is generated. If the pathology department is not computerized or does not use ICD-O codes to code histology, the registrar must manually review each pathology report. Some cancer registrars arrange with the pathology department
The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute was used for the
Fig. 2 Photomicrograph of poorly-differentiated rhabdomyosarcoma
Fig. 3 Pictomicrograph of retroperitoneal lymph node with rhabdomyosarcoma involvement with insert showing strong positive staining for desmin in tumor tissue (normal lymph node tissue delineated with red arrows, rest of slide is all tumor)
Virchows Arch (2014) 465:697–701
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to automatically have copies of all pathology reports sent to the registry for review so that the registrar can determine which are reportable. Both computerized and manual methods of reviewing pathology reports are required to include a way to track reports to ensure that each report has been included in the registrar’s review. Patients were considered to have not undergone RPLND if the patient was coded “no nodes were examined” in the variable “regional nodes examined (1988)”; “no regional LN removed” in the variable “scope of regional LN surgery (1998–2002)”; or “no regional LNs removed or aspirated, diagnosed at autopsy,” “biopsy or aspiration of regional LN, not otherwise specified (NOS),” or “sentinel LN biopsy” in the “treatment summary-scope of regional surgery (2003)” variable. The same three variables were used to define patients who underwent RPLND if greater than one LN were examined if the above coding was not specified. Tumor size was specified using SEER variables for tumor size “EOD (Extension of disease) 10-size (1988–2003)” and “CS tumor size (2004+)”. Pathologically documented metastasis to retroperitoneal LNs was defined using SEER variable “Regional nodes positive (1988+)”. SAS software (V9.3, Cary, NC) was used for statistical analysis to evaluate the association between different patient and tumor characteristics
Table 1 Demographics of patients with paratesticular rhabdomyosarcoma who underwent pathologic examination of the retroperitoneal lymph nodes (n=67)
Results Patient characteristics Table 1 summarizes demographics and primary tumor characteristics of 67 males with PTRMS treated with RPLND identified in the SEER database between 1973 and 2010. Demographics showed that 49 patients were white (73.1 %), 12 were black (17.9 %), and 5 were designated as other (7.5 %). The mean age at diagnosis was 14.9±9.5 years. Tumor characteristics The site of the primary tumor was the testis in 43 cases (64.2 %), the spermatic cord in 5 cases (7.5 %), the scrotum in 14 cases (20.9 %), and the epididymis in 5 cases (7.5 %). Embryonal rhabdomyosarcoma constituted 67.2 % of cases,
Characteristic
Age Tumor size Race
Site
Histology
Laterality RLN rhabdomyosarcoma lymph node, NS not significant, NOS not otherwise specified
and the incidence of LN metastasis on RPLND. Chi square and Fisher exact tests were used for determining significance of categorical variables. Odds ratios (OR) are presented with 95 % confidence intervals (CI). Statistical significance was determined with an alpha of 0.05.
Total
n (% of total)
RLN-negative n (% of group)
RLN-positive n (% of group)
p value
ORIGINAL ARTICLE
Primary tumor size predicts pathologic findings in the retroperitoneal lymph nodes in patients with paratesticular rhabdomyosarcoma Shaheen Alanee & Bradley Holland & Danuta Dynda & Onsi Kamel & Sabha Ganai
Received: 3 August 2014 / Revised: 14 September 2014 / Accepted: 29 September 2014 / Published online: 8 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract To determine patient and tumor characteristics that could predict pathologic findings after retroperitoneal lymph node dissection (RPLND) in paratesticular rhabdomyosarcoma (PTRMS), a total of 266 cases of PTRMS diagnosed between 1973 and 2010 were identified from a national database. RPLND dissection was performed in 67 patients, with a mean age of 14.9 years and median survival of 80 months. PTRMS occurred more often on the right side, had embryonal histology, and had an average size of 6.7 cm. Retroperitoneal lymph node (RPLN) metastasis occurred in 40 % (n=27) of patients. Tumor size and age were strong predictors of finding rhabdomyosarcoma in the retroperitoneal lymph nodes when examined by pathologists. Primary tumors larger than 7 cm in size developing in males 12 years or older had four times more odds of being associated with positive findings on pathologic examinations of the retroperitoneal lymph nodes. Patient race, histology, and tumor laterality were not significant predictors of PTRMS metastasis to the RPLN basin. Patients 12 years or older with PTRMS larger than 7 cm have a significant risk of retroperitoneal lymph nodes involvement with PTRMS. Detailed pathologic examination of the lymph nodes in these patients is recommended.
S. Alanee (*) : B. Holland : S. Ganai Department of Surgery, Division of Urology and Division of Surgical Oncology, Southern Illinois University School of Medicine, PO Box 19665, Springfield, IL 62794-9665, USA e-mail: [email protected] D. Dynda Center for Clinical Research, Southern Illinois University School of Medicine, PO Box 19665, Springfield, IL 62794-9665, USA O. Kamel Department of Pathology, Southern Illinois University School of Medicine, PO Box 19665, Springfield, IL 62794-9665, USA
Keywords Paratesticular neoplasm . Primary tumor size . Retroperitoneal lymph node . Rhabdomyosarcoma . SEER database
Introduction We recently examined a male patient in his second decade of life who presented with a right scrotal mass that rapidly increased in size over 6 months. Ultrasound of the scrotum demonstrated a 6.5×3.5×5.2 cm mass that involved the epididymis and was distinct from the testis (Fig. 1). Tumor markers (β-human choriogonadotropin, alpha fetoprotein, and lactic dehydrogenase) were normal and computerized tomography (CT) of the chest, abdomen, and pelvis did not show any signs of metastasis. Considering the rapid tumor growth, orchiectomy was advised and performed promptly. Pathologic examination of the mass revealed poorlydifferentiated paratesticular rhabdomyosarcoma (PTRMS; Fig. 2). After multidisciplinary discussion with concern for the patient’s age of presentation, positron emission tomography (PET) was recommended for further staging. While PET/ CT was negative for macroscopic metastatic disease, the patient was advised to have retroperitoneal lymph node dissection (RPLND) based on evidence showing microscopic pathologic nodal involvement in 17 % of patients without radiographic evidence of disease [3, 17]. Final pathologic examination of the retroperitoneal lymph nodes (LN) did indeed show the presence of rhabdomyosarcoma in those lymph nodes (Fig. 3) in spite of the negative imaging studies performed prior to surgery. PTRMS is the most common primary tumor of the mesenchymal-supporting tissue of the testes in males diagnosed under 36 years of age, with a mean age of 10 years [9, 12, 13]. The treatment of this disease is primarily based on chemotherapy, and controversy persists regarding the
698
Virchows Arch (2014) 465:697–701
Fig. 1 Ultrasound of the right testicle. a Transverse view of superior testis showing uninvolved epididymis. b Transverse view of inferior testis demonstrating paratesticular rhabdomyosarcoma (tumor indicated with white arrow)
diagnostic and therapeutic role of RPLND. CT scan has been suggested to predict retroperitoneal LN metastasis in PTRMS as an adequate substitute for pathologic examination of LN removed with RPLND, but multiple studies have documented imaging to miss cases of LN involvement, leading to increased local recurrence [16]. Therefore, it is important to better understand the relationship between patient and disease factors and the incidence of positive pathologic findings in the retroperitoneal LN. Tumor size has previously been shown to be associated with LN metastasis in other malignancies [11, 18], but the relationship between size and metastasis has not been investigated in PTRMS despite the fact that tumor size can be easily appreciated by clinical or radiologic examination. In this study, we focused on effect of primary tumor size and other tumor and patient factors on the incidence of pathologically documented LN metastasis in patients with PTRMS. Recognizing the low incidence of PTRMS, a large national database was used to perform our analysis.
Methods
purpose of this analysis [9]. SEER is a population-based cancer registry that routinely collects high-quality patient data from 17 registries in 14 states and represents an estimated 28 % of the US population. The SEER database was queried, after institutional review board determination, for the diagnosis of PTRMS from 1973 to 2010 using SEER*Stat software version 8.1.2 [10]. PTRMS cases were identified using the third edition of the International Classification of Diseases for Oncology (IDC-O-3) codes 8900 to 8904, 8910, 8912, 8920 to 8921, and 8991 and primary anatomical site codes of C62.0, C62.1, C62.9, C63.0, C63.1, and C63.2, which respectively code for undescended testis, descended testis, testis, epididymis, spermatic cord, and scrotum. Typically, SEER obtains histological confirmation of more than 90 % of all cancers. SEER requires reviewing all pathology reports to complete cancer reporting. If the pathology department is computerized and each report contains an ICD-O histology and behavior code, a computerized list of diagnoses is generated. If the pathology department is not computerized or does not use ICD-O codes to code histology, the registrar must manually review each pathology report. Some cancer registrars arrange with the pathology department
The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute was used for the
Fig. 2 Photomicrograph of poorly-differentiated rhabdomyosarcoma
Fig. 3 Pictomicrograph of retroperitoneal lymph node with rhabdomyosarcoma involvement with insert showing strong positive staining for desmin in tumor tissue (normal lymph node tissue delineated with red arrows, rest of slide is all tumor)
Virchows Arch (2014) 465:697–701
699
to automatically have copies of all pathology reports sent to the registry for review so that the registrar can determine which are reportable. Both computerized and manual methods of reviewing pathology reports are required to include a way to track reports to ensure that each report has been included in the registrar’s review. Patients were considered to have not undergone RPLND if the patient was coded “no nodes were examined” in the variable “regional nodes examined (1988)”; “no regional LN removed” in the variable “scope of regional LN surgery (1998–2002)”; or “no regional LNs removed or aspirated, diagnosed at autopsy,” “biopsy or aspiration of regional LN, not otherwise specified (NOS),” or “sentinel LN biopsy” in the “treatment summary-scope of regional surgery (2003)” variable. The same three variables were used to define patients who underwent RPLND if greater than one LN were examined if the above coding was not specified. Tumor size was specified using SEER variables for tumor size “EOD (Extension of disease) 10-size (1988–2003)” and “CS tumor size (2004+)”. Pathologically documented metastasis to retroperitoneal LNs was defined using SEER variable “Regional nodes positive (1988+)”. SAS software (V9.3, Cary, NC) was used for statistical analysis to evaluate the association between different patient and tumor characteristics
Table 1 Demographics of patients with paratesticular rhabdomyosarcoma who underwent pathologic examination of the retroperitoneal lymph nodes (n=67)
Results Patient characteristics Table 1 summarizes demographics and primary tumor characteristics of 67 males with PTRMS treated with RPLND identified in the SEER database between 1973 and 2010. Demographics showed that 49 patients were white (73.1 %), 12 were black (17.9 %), and 5 were designated as other (7.5 %). The mean age at diagnosis was 14.9±9.5 years. Tumor characteristics The site of the primary tumor was the testis in 43 cases (64.2 %), the spermatic cord in 5 cases (7.5 %), the scrotum in 14 cases (20.9 %), and the epididymis in 5 cases (7.5 %). Embryonal rhabdomyosarcoma constituted 67.2 % of cases,
Characteristic
Age Tumor size Race
Site
Histology
Laterality RLN rhabdomyosarcoma lymph node, NS not significant, NOS not otherwise specified
and the incidence of LN metastasis on RPLND. Chi square and Fisher exact tests were used for determining significance of categorical variables. Odds ratios (OR) are presented with 95 % confidence intervals (CI). Statistical significance was determined with an alpha of 0.05.
Total
n (% of total)
RLN-negative n (% of group)
RLN-positive n (% of group)
p value
