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Carcinoma of lung with rhabdoid features
Carcinoma of Lung With Rhabdoid Features PHEROZE TAMBOLI, MD, TUSHAR H. TOPRANI, MD, ´N ˜ EZ, MD, MITUAL B. AMIN, MD, JUNG SIL RO, MD, NELSON G. ORDO ALBERTO G. AYALA, MD, AND JAE Y. RO, MD, PHD Lung tumors with rhabdoid features, included as variants of large cell carcinoma in the 1999 World Health Organization classification of lung tumors, are rare and have an aggressive clinical course. We report 11 patients with primary lung tumors with rhabdoid features and review the literature on this uncommon tumor. We examined samples from 7 primary (6 resections, 1 biopsy) and 4 metastatic tumor samples. All specimens were stained with immunohistochemical stains for pancytokeratin (CK), cytokeratin 7 (CK7), cytokeratin (CK20), thyroid transcription factor-1 (TTF-1), and vimentin. The patients were 7 men and 4 women whose ages ranged from 35 to 70 years. Nine patients presented with respiratory symptoms, and 9 patients had a history of heavy smoking. One patient had TNM stage I tumor, 3 had stage III tumors, and 6 had stage IV tumors at presentation; tumor stage could not be determined in 1 patient. Histological examination of these tumors showed typical rhabdoid cells: large cells with abundant cytoplasm, a large eccentric nucleus with a central macronucleolus, and a rounded eosinophilic cytoplasmic inclusion that sometimes caused nuclear indentation. These cells
constituted 10% to 90% of the tumor. The “parent” neoplasm was sarcomatoid carcinoma and adenocarcinoma in 4 cases each and was large cell undifferentiated carcinoma in 3 cases. Cytoplasmic staining in the rhabdoid cells was seen in 9 of 11 cases for CK, in 4 of 10 cases for CK7, and in all 11 cases for vimentin. Nuclear staining for TTF-1 in the rhabdoid cells was absent in all 11 cases, and cytoplasmic staining for CK20 was negative in the rhabdoid cells in all 10 cases studied. Of the 9 patients with available follow-up information, 8 died of disease, and 1 is alive with no evidence of disease 20 months after the initial diagnosis. We conclude that rhabdoid features can occur in a variety of lung tumors, including sarcomatoid carcinoma. Recognizing these lesions is important because of their possibly aggressive clinical course. HUM PATHOL 35:8-13. © 2004 Elsevier Inc. All rights reserved. Key words: lung carcinoma, rhabdoid, immunohistochemistry. Abbreviations: CK, pancytokeratin; CK7, cytokeratin 7; CK20, cytokeratin 20; TTF-1, thyroid transcription factor-1.
Rhabdoid tumor was first reported in the kidney as a distinct tumor that occurred in children.1,2 The rhabdoid cells of these tumors were reportedly characterized by the presence of a rounded eosinophilic cytoplasmic inclusion within large cells with abundant cytoplasm and by the presence of a large eccentric nucleus with a central macronucleolus. Subsequently, tumors with similar morphological characteristics were reported in various extrarenal sites.3-17 Many of these lesions, unlike the renal tumors, were generally mixed with a carcinoma or a mesenchymal neoplasm. These neoplasms are characterized by an aggressive course and poor prognosis. The first case reported of a rhabdoid tumor in the lung was described by Colby et al18 in 1995, as neuroendocrine carcinoma with rhabdoid phenotype. This patient was also included in the series of 6 cases that was subsequently reported by Cavazza et al in 1996.19 Additional cases have since been reported.13,20-25 In the 1999 World Health Organization classification of lung tumors, the rhabdoid phenotype has been included as a variant of large cell carcinoma.26 The aims of our study were to report the clinicopathologic features of 11 cases of lung carcinoma with rhabdoid features and to review the literature on this
uncommon tumor. To our knowledge, this constitutes the largest series of these rare tumors that arise in the lung. MATERIALS AND METHODS Lung tumors with rhabdoid features were identified during routine histological examination of lung cancer specimens at The University of Texas MD Anderson Cancer Center. Clinical information and follow-up status in these 11 patients was obtained by reviewing the patients’ records. The tumors were staged according to the 1997 TNM staging system.27 The diagnosis of lung carcinoma with rhabdoid features was established when ⱖ10% of the tumor cells showed morphological characteristics that are typical of rhabdoid tumor. All available hematoxylin and eosin slides were reviewed. These included the lobectomy specimen of the primary lung tumor in 6 patients, needle biopsy of the primary lung tumor in 1 patient, and resected metastatic lesions (from lymph node, jejunum, and soft tissue of the chest wall) in the remaining 4 patients. Immunohistochemical studies were performed on formalin-fixed paraffin-embedded tissue sections with the LSAB2 peroxidase kit (DAKO Corporation, Carpinteria, CA) in a DAKO Autostainer (DAKO). Heat-induced epitope retrieval procedure was used to enhance the immunostaining. The primary antibodies used included the following: cytokeratin cocktail (clone AE1 and clone AE3 mouse monoclonal antibodies at 1:200 dilution [Boehringer Mannheim Corp., Indianapolis, IN] and CAM 5.2 at 1:5 dilution [Becton-Dickinson, Mountainview, CA]), cytokeratin 7 (CK7; clone OV-TL 12/30, 1:50 dilution; DAKO), cytokeratin 20 (CK20; clone KS20.8, 1:40 dilution; DAKO), thyroid transcription factor 1 (TTF-1; clone 8G7G3/1, 1:20 dilution; DAKO), and vimentin monoclonal antibodies (clone V9, 1:500 dilution; DAKO). Known positive and negative tissues were used as controls.
From the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. Accepted for publication July 31, 2003. Address correspondence and reprint requests to Pheroze Tamboli, MD, Department of Pathology, M.D. Anderson Cancer Center, Box 85, 1515 Holcombe Boulevard, Houston, TX 77030. 0046-8177/$—see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2003.07.019
8
CARCINOMA OF LUNG WITH RHABDOID FEATURES (Tamboli et al)
TABLE 1. Clinicopathologic Features Sex/age No. (yr)
Symptoms
Smoking history
Location/ Maximum dimension (cm)
Site of metastases
1 2 3
M/57 F/57 M/54
Respiratory Hemoptysis Hemoptysis
Yes Yes Yes
LUL/23 LUL/4.0 RUL/4.0
Not known Brain and jejunum Liver, bone, lymph node Lung, lymph node Soft tissue, bowel, lymph node Bone, chest wall
4 5
F/48 M/54
Yes NA
RUL/5.1 RUL/10
6
M/70
Yes
Left lung/NA
7 8
M/61 F/59
Hoarseness Hemoptysis, GI bleeding Knot in right lateral chest wall Hemoptysis Cough
Yes Yes
RUL/4.7 RML/NA
9 10
M/34 M/65
NA NA
LLL/2.0 LLL/NA
11
F/59
Hemoptysis Mass in the chest wall Hemoptysis
Lymph node, bone Brain, bone, lung, lymph node Lung Chest wall
Yes
LLL/3.0
Lymph node
% Rhabdoid Follow-up cells status (mo)
TNM stage
Associated tumor type
NA I IV
Sarcomatoid carcinoma Large cell undifferentiated carcinoma Large cell undifferentiated carcinoma
25 90 15
LFU DOD (11) DOD (4)
IIIB IV
Adenocarcinoma Large cell undifferentiated carcinoma
10 90
DOD (19) DOD (5)
IV
Adenocarcinoma
90
DOD (10)
IIIA IV
Sarcomatoid carcinoma Adenocarcinoma
30 50
DOD (15) DOD (3)
IV IV
Sarcomatoid carcinoma Sarcomatoid carcinoma
60 75
DOD (3) LFU
IIIA
Adenocarcinoma
20
ANED (20)
Abbreviations: ANED, alive with no evidence of disease; DOD, dead of disease; F, female; GI, gastrointestinal; LFU, lost to follow-up; LLL, left lower lobe; LUL, left upper lobe; M, male; NA, not available; RML, right middle lobe; RUL, right upper lobe.
RESULTS Clinical Findings
10% and 20% in the adenocarcinomas; and 90% in the large cell undifferentiated carcinoma. The lung tumor that was diagnosed on a needle biopsy specimen showed adenocarcinoma, with 50% of cells having rhabdoid morphology. Among the 4 patients with resected metastatic lesions, the histological diagnosis was large cell undifferentiated carcinoma in 2 patients (with 15% and 90% rhabdoid cells) and sarcomatoid carcinoma in 1 patient (75% rhabdoid cells). The metastases from the fourth patient contained ⬎90% rhabdoid cells. In all 11 cases, the rhabdoid component was characterized by the presence of large cells with abundant eosinophilic cytoplasm, a large eccentric nucleus with a central macronucleolus, and a rounded eosinophilic cytoplasmic inclusion that sometimes caused nuclear indentation (Fig 1).
Salient clinicopathologic features are presented in Table 1. The patients were 7 men and 4 women, who ranged in age from 35 to 70 years (mean age: 56.2 years, median age: 57 years). There was a history of heavy smoking in all 9 patients for whom this information was available. The tumor was located on the left side in 6 patients and on the right side in 5. At presentation, the tumors were staged as follows: TNM stage I, 1 patient; stage III, 3 patients; and stage IV, 6 patients. The tumor stage could not be determined in 1 patient. At initial presentation, 4 patients had metastases beyond the regional lymph nodes. One of these patients had an earlier resection of a lung tumor at another institution, whereas the other 3 had radiological evidence of lung tumor. The most common site for metastases was lymph nodes; this occurred in 6 patients, 4 of whom had metastases to extramediastinal nodal sites. Intrapulmonary metastases were noted radiologically in 3 patients. Other sites of metastases included bone (3 patients), soft tissue (3 patients), brain (2 patients), small intestine (2 patients), and liver (1 patient).
Immunohistochemical Findings The results of immunohistochemical staining are summarized in Table 2. The paranuclear inclusions in the rhabdoid cells stained for pancytokeratin (CK) in 9 of 11 cases and for vimentin in all 11 cases (Fig 2). Cytoplasmic, paranuclear staining for CK7 was seen in 4 of 10 cases. The rhabdoid cells were negative for CK20 in the 10 cases investigated for this marker. No expression for TTF-1 was seen in any of the 11 cases.
Pathological Findings The resected primary tumors were 3.0, 4.0, 4.7, 5.1, and 23 cm in diameter, respectively, in 5 of 6 patients; no information on tumor size was available for the patient who had undergone resection at a different institution. These 5 tumors were described as well circumscribed, with a gray-white to tan-yellow cut surface showing focal areas of hemorrhage and necrosis. Histologically, the primary tumors were sarcomatoid carcinoma in 3 patients, adenocarcinoma in 2 patients, and large cell undifferentiated carcinoma in 1 patient. The proportions of rhabdoid cells in these tumors were 25%, 30%, and 60% in the sarcomatoid carcinomas;
Clinical Outcome Two of our 11 patients were lost to follow-up after the initial visit. For the remaining 9 patients, the follow-up period ranged from 3 to 20 months, with a mean and median of 10 months. Eight of the 9 patients (89%) died of disease, at 3, 3, 4, 5, 10, 11, 15, and 19 months after diagnosis. One patient is alive with no evidence of disease at 20 months. 9
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Volume 35, No. 1 (January 2004)
logical features and have been shown to have many similarities on immunohistochemical staining.29 The hallmark of rhabdoid cells is a large paranuclear, hyaline, often globular eosinophilic cytoplasmic inclusion that sometimes causes nuclear indentation.1,19 Ultrastructurally, this inclusion is composed of cytoplasmic intermediate filaments that are arranged in a concentric, whorl-like pattern.1,19,22 On occasion, some of these cells have been reported to have variable numbers of dense core-type granules that represent neuroendocrine differentiation.19 A transition between nonrhabdoid and rhabdoid tumor cells has been variably noted,13,19,21 with the rhabdoid cells observed mainly at the periphery of the tumor.21 Most extrarenal rhabdoid tumors show a combined morphology, with the rhabdoid component and an epithelial or mesenchymal component. Wick et al30 proposed the term composite extrarenal rhabdoid tumor for tumors that are composed of both a recognized entity, such as adenocarcinoma, and a population of tumor cells with rhabdoid features. They also suggested that tumors composed exclusively of rhabdoid cells should be labeled malignant extrarenal rhabdoid tumors. In addition, they indicated that because the “rhabdoid” phenotype is seen in a heterogeneous group of lesions of dissimilar histogenesis, this phenotype may represent a “common endpoint of clonal evolution” in tumors of clearly different origins.30 Indeed, most of the cases of lung tumors with rhabdoid features that have been reported in the literature, as well as those that we have studied, have a recognizable “parent” lung carcinoma associated with the rhabdoid cell component. Thus, lung tumors with rhabdoid features seem to fit into the category of composite extrarenal rhabdoid tumor as suggested by Wick et al.30 In our patients, the parent neoplasm was sarcomatoid carcinoma (4 cases), adenocarcinoma (4 cases), and large cell undifferentiated carcinoma (3 cases). Cavazza et al19 suggested that to qualify for such a diagnosis in the lung, rhabdoid cells should comprise ⱖ10% of the tumor cells. This was reiterated by Shimazaki et al,23 who found that tumors with ⬎10% rhabdoid cells behaved more aggressively than did those with ⬍10% rhabdoid cells. Those investigators also found that tumors with ⬍5% rhabdoid cells behaved similarly to large cell carcinoma without rhabdoid cells.23 Only those patients in whom the rhabdoid component of the tumors constituted ⱖ10% of the total tumor are included in this review. On the basis of this criterion, only 21 cases of patients with rhabdoid lung tumors have been published so far.13,19-25 Clinicopathologic features of those 21 patients are summarized in Table 3. The 32 patients (21 previously reported and 11 from the present series) of rhabdoid lung tumors range in age from 25 to 82 years (mean, 56.9 years; median, 57 years). The patients were 20 men and 12 women. The most common presenting symptoms, reported in 23 patients, were respiratory, including cough, hemoptysis, chest pain, hoarseness, and dyspnea. There was a
FIGURE 1. (A) Rhabdoid cells arranged in an alveolar pattern (⫻100). (B) High power showing rhabdoid cells with typical paranuclear cytoplasmic inclusions (⫻400).
DISCUSSION Renal rhabdoid tumor was first described as a distinct clinicopathologic entity occurring in a pediatric population and was characterized by a poor survival rate.1,2 This type of tumor had pure rhabdoid morphology highlighted by the proliferation of typical monotonous rhabdoid cells.28 Since then, extrarenal tumors with rhabdoid morphology have generated much interest and have been described in various other locations such as soft tissue, liver, uterus, skin, brain, prostate, vulva, urinary bladder, orbit, intestine and stomach, tongue, and recently, the lungs.3-17,19-25 Although renal rhabdoid tumors are tumors of childhood, extrarenal rhabdoid tumors are observed in a broad range of age groups.4 Even though rhabdoid tumors of the kidney and extrarenal rhabdoid tumors are considered to be separate entities, the rhabdoid cells have similar morpho10
CARCINOMA OF LUNG WITH RHABDOID FEATURES (Tamboli et al)
TABLE 2. Results of Immunohistochemical Staining Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Case 8
Case 9
Case 10
Case 11
IHC stains
R
NR
R
NR
R
NR
R
NR
R
R
R
NR
R
NR
R
NR
R
NR
R
NR
CK CK7 CK20 TTF-1 Vimentin
⫹, F ⫺ ⫺ ⫺ ⫹
⫹, F ⫺ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹, F ⫹
⫹ ⫹ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹ ⫹, F
⫹ ⫹ ⫺ ⫺ ⫹, F
⫹ ⫹ ⫺ ⫺ ⫹, F
⫹ ⫺ ⫺ ⫺ ⫹
⫹, F ⫺ ⫺ ⫺ ⫹
⫺ ⫺ ⫺ ⫺ ⫹
⫺ ⫺ ⫺ ⫺ ⫹, F
⫹ ND ND ⫺ ⫹, F
⫹ ND ND ⫹ ⫺
⫺ ⫺ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹, F ⫹, F
⫹ ⫺ ⫺ ⫺ ⫹
⫹ ⫺ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹, F ⫺
Abbreviations: CK, pancytokeratin; CK7, cytokeratin 7; CK20, cytokeratin 20; F, focally; IHC, immunohistochemical; ND, not done; NR, nonrhabdoid; R, rhabdoid; TTF-1, thyroid transcription factor-1.
These findings seem to indicate that CK7 and TTF-1 are of limited value in determining the site of origin of an extrarenal rhabdoid tumor. Therefore, clinical and radiological data are required to exclude a primary tumor located elsewhere, before a diagnosis of a tumor with rhabdoid features is considered to be a lung primary. These tumors have also been variably reported to show neuroendocrine differentiation.19,21,23,29 Thus, there are reports of combined large cell neuroendocrine carcinoma with rhabdoid cells.20 In addition, Leu-7 and glial fibrillary acidic protein have been reported to be positive in a few cases.19 These tumors may be considered to be aggressive, as the majority present with high-stage disease. Among the 17 patients (including 10 of our patients) for whom data on tumor TNM stage were available, 2 presented with stage I disease, 9 with stage III disease, and 6 with stage IV disease. Information on the site of the metastases was available in 20 patients, with the lymph node being the most common site of metastases. The clinical follow-up on these 32 cases ranged from 22 days to 60 months, with a mean of 8.3 months. Nineteen of the 32 (60%) patients died of disease, with survival time ranging from 0.6 to 36 months (mean survival of 8.1 months, median of 5 months). Three were alive with disease, and 3 were alive with no evidence of disease. Two other patients were alive, but their status was not known. One patient died of other causes. No information was available for 1 patient, and the remaining 3 patients were lost to follow-up. Clearly these tumors behave aggressively; however, it is not certain whether these patients do worse than TNM stage–matched patients who have advanced non–small cell lung carcinoma. Comparing the survival rates for cases of rhabdoid lung tumors and historic cases of advanced-stage non–small cell lung carcinoma is also difficult because of the heterogeneity of the study population and the variation in survival rates of patients with advanced non–small cell lung carcinoma (10% to 40% 1-year survival). Also, in keeping with the purported aggressive nature of these tumors, Miyagi et al21 have reported strong positive staining for proliferating cell nuclear antigen in the rhabdoid cells (⬎60%), in contrast to scattered staining in the nonrhabdoid component of the tumor, showing that the rhabdoid cells are highly proliferative.
history of heavy smoking in 19 of the 24 patients for whom this information was available. The size of the primary tumor (reported in 23 patients) ranged from 2.0 cm to 23.0 cm (mean, 7.0 cm). Eighteen tumors occurred on the right side and 14, on the left. The amount of the rhabdoid component of the tumors ranged from 10% to 90% and was associated with 12 cases of adenocarcinoma, 7 cases of large cell undifferentiated carcinoma, 4 cases of sarcomatoid carcinoma, 4 cases of poorly differentiated carcinoma, 3 cases of large cell neuroendocrine carcinoma, and 1 case of sarcoma; 1 case was reported as an extrarenal rhabdoid tumor occurring in the lung, with no mention of an associated parent tumor. It should be noted that almost all of these tumors have been reported to be carcinomas, with the exception of 1 case with sarcomalike features that was reported by Cavazza et al.19 These tumors usually express both vimentin and epithelial markers (CK or epithelial membrane antigen),13,19-21,23,25 although a few tumors that do not express epithelial markers have been reported.19,22,24 Although all the cases in our study did stain for vimentin, 2 of the 11 cases showed no reactivity for CK. In 10 of our cases, 4 were positive for CK7, and all 10 were negative for CK20. All 11 cases were negative for TTF-1.
FIGURE 2. Immunoperoxidase stain for vimentin showing positivity for the cytoplasmic inclusions (⫻400).
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HUMAN PATHOLOGY
Volume 35, No. 1 (January 2004)
TABLE 3. Summary of Reported Cases of Lung Tumors With Rhabdoid Features
Reference
Sex/age No. (yr)
Symptoms
Location/ Smoking maximum history dimension (cm)
Site of metastases
TNM stage
Associated tumor type
1
F/54
Hemoptysis
Yes
RUL/NA
Lymph node
NA Large cell carcinoma
2 3 4 5 6 7
M/36 M/47 F/71 M/71 F/25 M/74
Chest pain Hemoptysis NA NA Bazex’s syndrome Incidental finding
NA Yes NA NA No Yes
LUL/NA RLL/NA LUL/NA RLL/NA LLL/NA LLL/3.5
NA NA Lymph node NA Lung, lymph node NA
NA NA NA NA NA NA
8 9 10
M/68 F/62 M/40
No Yes No
RML/3 RUL/11 RUL/6
Lymph node Present NA
NA Adenocarcinoma NA LCNEC NA Adenocarcinoma
F/50
Cough and hemoptysis Cough and hemoptysis Cough, chest pain, dyspnea Cough and dyspnea
Yes
LLL/17
Lymph node
12
M/53
Cough and hemoptysis
Yes
LUL/12
NA
Miyagi et al21 13 14 15 16 Shimazaki et al23 17
M/51 M/72 F/50 M/69
Hemoptysis Cough Fatigue Abnormal chest X-ray
Yes No No N/A
RUL/4 RUL/5.6 RML/3.0 RLL/4.5
Lymph node Lymph node NA None
M/66
Hemoptysis
NA
LUL/6.0
None
18
M/82
Yes
LUL/11.0
None
19
F/47
Chest pain, cough, dyspnea Hemoptysis and cough
Yes
RUL/8.5
None
20
F/69
Chest pain
Yes
21
M/59
NA
Yes
NA LCNEC, small cell carcinoma NA LCNEC, small cell carcinoma, SCC IIIA Adenocarcinoma IIIA Adenocarcinoma IA Adenocarcinoma IIIA Poorly differentiated tumor IIIB Poorly differentiated tumor IIIA Poorly differentiated tumor IIIA Poorly differentiated tumor NA Pseudomesotheliomatous adenocarcinoma NA Large cell carcinoma
Cavazza et al19
Rubenchik et al22 Chetty et al13
Chetty et al20 11
Attems and Lintner24 Kaneko et al25
RUL/2.0-cm-thick Duodenum, skin, pleural rind adrenal gland RUL/4.5 Adrenal gland
Sarcoma Adenocarcinoma Adenocarcinoma Large cell carcinoma Large cell carcinoma NA
% Rhabdoid Follow-up cells status (mo) 90
AWD (6)
⬎10 ⬎10 10 ⬎10 10 Most
AWD (4) DOD (4) AWD (2) ASU (5) NA ANED (24)
⬎10 25 ⬎10
DOD (6) DOD (3) LFU (6)
15
DOD (6)
10
DOD (12)
70 90 50 18.2
DOD (36) DOD (4) ASU (41) DOD (1.5)
15.5
DOD (0.6)
15
DOD (1)
60
DOD (10)
NA
Dead, other disease (3) ANED (60)
90
Abbreviations: ANED, alive with no evidence of disease; ASU, alive, status unknown; AWD, alive with disease; DOD, dead of disease; F, female; LCNEC, large cell neuroendocrine carcinoma; LLL, left lower lobe; LUL, left upper lobe; M, male; NA, not available; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe; SCC, squamous cell carcinoma.
A pathologic and immunohistochemical study. Am J Surg Pathol 13:848-858, 1989 8. Carter RL, McCarthy KP, al-Sawm SZ, et al: Malignant rhabdoid tumour of the bladder with immunohistochemical and ultrastructural evidence suggesting histiocytic origin. Histopathology 14: 179-190, 1989 9. Harris M, Eyden BP, Joglekar VM: Rhabdoid tumour of the bladder: A histological, ultrastructural and immunohistochemical study. Histopathology 11:1083-1092, 1987 10. Walford N, Deferrai R, Slater RM, et al: Intraorbital rhabdoid tumour following bilateral retinoblastoma. Histopathology 20: 170-173, 1992 11. Niffenegger JH, Jakobiec FA, Shore JW, et al: Adult extrarenal rhabdoid tumor of the lacrimal gland. Ophthalmology 99:567574, 1992 12. Chetty R, Bhathal PS: Caecal adenocarcinoma with rhabdoid phenotype: An immunohistochemical and ultrastructural analysis. Virchows Arch A Pathol Anat Histopathol 422:179-182, 1993 13. Chetty R, Bhana B, Batitang S, et al: Lung carcinomas composed of rhabdoid cells. Eur J Surg Oncol 23:432-434, 1997 14. Ueyama T, Nagai E, Yao T, et al: Vimentin-positive gastric carcinomas with rhabdoid features. A clinicopathologic and immunohistochemical study. Am J Surg Pathol 17:813-819, 1993 15. Patron M, Palacios J, Rodriguez-Peralto JL, et al: Malignant rhabdoid tumor of the tongue. A case report with immunohistochemical and ultrastructural findings. Oral Surg Oral Med Oral Pathol 65:67-70, 1988 16. Small EJ, Gordon GJ, Dahms BB: Malignant rhabdoid tumor of the heart in an infant. Cancer 55:2850-2853, 1985 17. Batsakis JG, Manning JT: Malignant rhabdoid tumor. Ann Otol Rhinol Laryngol 97:690-691, 1988
In conclusion, lung tumors with rhabdoid cells are uncommon tumors that may behave aggressively. The presence of a rhabdoid component in a lung tumor should be reported, and the clinician should be alerted about the possibly aggressive nature of this tumor. REFERENCES 1. Haas JE, Palmer NF, Weinberg AG, et al: Ultrastructure of malignant rhabdoid tumor of the kidney. A distinctive renal tumor of children. HUM PATHOL 12:646-657, 1981 2. Beckwith JB, Palmer NF: Histopathology and prognosis of Wilms tumors: Results from the First National Wilms’ Tumor Study. Cancer 41:1937-1948, 1978 3. Cattani MG, Viale G, Santini D, et al: Malignant rhabdoid tumour of the uterus: An immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat Histopathol 420:459-462, 1992 4. Parham DM, Weeks DA, Beckwith JB: The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. Am J Surg Pathol 18:1010-1029, 1994 5. Ekfors TO, Aho HJ, Kekomaki M: Malignant rhabdoid tumor of the prostatic region. Immunohistological and ultrastructural evidence for epithelial origin. Virchows Arch A Pathol Anat Histopathol 406:381-388, 1985 6. Matias C, Nunes JF, Vicente LF, et al: Primary malignant rhabdoid tumour of the vulva. Histopathology 17:576-578, 1990 7. Perrone T, Swanson PE, Twiggs L, et al: Malignant rhabdoid tumor of the vulva: Is distinction from epithelioid sarcoma possible?
12
CARCINOMA OF LUNG WITH RHABDOID FEATURES (Tamboli et al) 18. Colby TV, Koss MN, Travis WD: Carcinoid and other neuroendocrine tumors, in Travis WD (ed): Tumors of the Lower Respiratory Tract. Washington, DC, Armed Forces Institute of Pathology, 1995, p 311 19. Cavazza A, Colby TV, Tsokos M, et al: Lung tumors with a rhabdoid phenotype. Am J Clin Pathol 105:182-188, 1996 20. Chetty R: Combined large cell neuroendocrine, small cell and squamous carcinomas of the lung with rhabdoid cells. Pathology 32:209-212, 2000 21. Miyagi J, Tsuhako K, Kinjo T, et al: Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma. Histopathology 37:37-44, 2000 22. Rubenchik I, Dardick I, Auger M: Cytopathology and ultrastructure of primary rhabdoid tumor of lung. Ultrastruct Pathol 20:355-360, 1996 23. Shimazaki H, Aida S, Sato M, et al: Lung carcinoma with rhabdoid cells: A clinicopathological study and survival analysis of 14 cases. Histopathology 38:425-434, 2001 24. Attems JH, Lintner F: Pseudomesotheliomatous adenocarci-
noma of the lung with rhabdoid features. Pathol Res Pract 197:841846, 2001 25. Kaneko T, Honda T, Fukushima M, et al: Large cell carcinoma of the lung with a rhabdoid phenotype. Pathol Int 52:643-647, 2002 26. Travis WD, Colby TV, Corrin B, et al: Histological Typing of Lung and Pleural Tumours. New York, Springer-Verlag, 1999, pp 40-42 27. Sobin LH, Wittekind C: Lung, in Sobin LH, Wittekind C (eds): TNM: Classification of Malignant Tumours (ed 5). New York, Wiley-Liss, 1997, pp 93-97 28. Weeks DA, Beckwith JB, Mierau GW, et al: Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms’ Tumor Study Pathology Center. Am J Surg Pathol 13:439-458, 1989 29. Kaiserling E, Ruck P, Handgretinger R, et al: Immunohistochemical and cytogenetic findings in malignant rhabdoid tumor. Gen Diagn Pathol 141:327-337, 1996 30. Wick MR, Ritter JH, Dehner LP: Malignant rhabdoid tumors: A clinicopathologic review and conceptual discussion. Semin Diagn Pathol 12:233-248, 1995
13
constituted 10% to 90% of the tumor. The “parent” neoplasm was sarcomatoid carcinoma and adenocarcinoma in 4 cases each and was large cell undifferentiated carcinoma in 3 cases. Cytoplasmic staining in the rhabdoid cells was seen in 9 of 11 cases for CK, in 4 of 10 cases for CK7, and in all 11 cases for vimentin. Nuclear staining for TTF-1 in the rhabdoid cells was absent in all 11 cases, and cytoplasmic staining for CK20 was negative in the rhabdoid cells in all 10 cases studied. Of the 9 patients with available follow-up information, 8 died of disease, and 1 is alive with no evidence of disease 20 months after the initial diagnosis. We conclude that rhabdoid features can occur in a variety of lung tumors, including sarcomatoid carcinoma. Recognizing these lesions is important because of their possibly aggressive clinical course. HUM PATHOL 35:8-13. © 2004 Elsevier Inc. All rights reserved. Key words: lung carcinoma, rhabdoid, immunohistochemistry. Abbreviations: CK, pancytokeratin; CK7, cytokeratin 7; CK20, cytokeratin 20; TTF-1, thyroid transcription factor-1.
Rhabdoid tumor was first reported in the kidney as a distinct tumor that occurred in children.1,2 The rhabdoid cells of these tumors were reportedly characterized by the presence of a rounded eosinophilic cytoplasmic inclusion within large cells with abundant cytoplasm and by the presence of a large eccentric nucleus with a central macronucleolus. Subsequently, tumors with similar morphological characteristics were reported in various extrarenal sites.3-17 Many of these lesions, unlike the renal tumors, were generally mixed with a carcinoma or a mesenchymal neoplasm. These neoplasms are characterized by an aggressive course and poor prognosis. The first case reported of a rhabdoid tumor in the lung was described by Colby et al18 in 1995, as neuroendocrine carcinoma with rhabdoid phenotype. This patient was also included in the series of 6 cases that was subsequently reported by Cavazza et al in 1996.19 Additional cases have since been reported.13,20-25 In the 1999 World Health Organization classification of lung tumors, the rhabdoid phenotype has been included as a variant of large cell carcinoma.26 The aims of our study were to report the clinicopathologic features of 11 cases of lung carcinoma with rhabdoid features and to review the literature on this
uncommon tumor. To our knowledge, this constitutes the largest series of these rare tumors that arise in the lung. MATERIALS AND METHODS Lung tumors with rhabdoid features were identified during routine histological examination of lung cancer specimens at The University of Texas MD Anderson Cancer Center. Clinical information and follow-up status in these 11 patients was obtained by reviewing the patients’ records. The tumors were staged according to the 1997 TNM staging system.27 The diagnosis of lung carcinoma with rhabdoid features was established when ⱖ10% of the tumor cells showed morphological characteristics that are typical of rhabdoid tumor. All available hematoxylin and eosin slides were reviewed. These included the lobectomy specimen of the primary lung tumor in 6 patients, needle biopsy of the primary lung tumor in 1 patient, and resected metastatic lesions (from lymph node, jejunum, and soft tissue of the chest wall) in the remaining 4 patients. Immunohistochemical studies were performed on formalin-fixed paraffin-embedded tissue sections with the LSAB2 peroxidase kit (DAKO Corporation, Carpinteria, CA) in a DAKO Autostainer (DAKO). Heat-induced epitope retrieval procedure was used to enhance the immunostaining. The primary antibodies used included the following: cytokeratin cocktail (clone AE1 and clone AE3 mouse monoclonal antibodies at 1:200 dilution [Boehringer Mannheim Corp., Indianapolis, IN] and CAM 5.2 at 1:5 dilution [Becton-Dickinson, Mountainview, CA]), cytokeratin 7 (CK7; clone OV-TL 12/30, 1:50 dilution; DAKO), cytokeratin 20 (CK20; clone KS20.8, 1:40 dilution; DAKO), thyroid transcription factor 1 (TTF-1; clone 8G7G3/1, 1:20 dilution; DAKO), and vimentin monoclonal antibodies (clone V9, 1:500 dilution; DAKO). Known positive and negative tissues were used as controls.
From the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. Accepted for publication July 31, 2003. Address correspondence and reprint requests to Pheroze Tamboli, MD, Department of Pathology, M.D. Anderson Cancer Center, Box 85, 1515 Holcombe Boulevard, Houston, TX 77030. 0046-8177/$—see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2003.07.019
8
CARCINOMA OF LUNG WITH RHABDOID FEATURES (Tamboli et al)
TABLE 1. Clinicopathologic Features Sex/age No. (yr)
Symptoms
Smoking history
Location/ Maximum dimension (cm)
Site of metastases
1 2 3
M/57 F/57 M/54
Respiratory Hemoptysis Hemoptysis
Yes Yes Yes
LUL/23 LUL/4.0 RUL/4.0
Not known Brain and jejunum Liver, bone, lymph node Lung, lymph node Soft tissue, bowel, lymph node Bone, chest wall
4 5
F/48 M/54
Yes NA
RUL/5.1 RUL/10
6
M/70
Yes
Left lung/NA
7 8
M/61 F/59
Hoarseness Hemoptysis, GI bleeding Knot in right lateral chest wall Hemoptysis Cough
Yes Yes
RUL/4.7 RML/NA
9 10
M/34 M/65
NA NA
LLL/2.0 LLL/NA
11
F/59
Hemoptysis Mass in the chest wall Hemoptysis
Lymph node, bone Brain, bone, lung, lymph node Lung Chest wall
Yes
LLL/3.0
Lymph node
% Rhabdoid Follow-up cells status (mo)
TNM stage
Associated tumor type
NA I IV
Sarcomatoid carcinoma Large cell undifferentiated carcinoma Large cell undifferentiated carcinoma
25 90 15
LFU DOD (11) DOD (4)
IIIB IV
Adenocarcinoma Large cell undifferentiated carcinoma
10 90
DOD (19) DOD (5)
IV
Adenocarcinoma
90
DOD (10)
IIIA IV
Sarcomatoid carcinoma Adenocarcinoma
30 50
DOD (15) DOD (3)
IV IV
Sarcomatoid carcinoma Sarcomatoid carcinoma
60 75
DOD (3) LFU
IIIA
Adenocarcinoma
20
ANED (20)
Abbreviations: ANED, alive with no evidence of disease; DOD, dead of disease; F, female; GI, gastrointestinal; LFU, lost to follow-up; LLL, left lower lobe; LUL, left upper lobe; M, male; NA, not available; RML, right middle lobe; RUL, right upper lobe.
RESULTS Clinical Findings
10% and 20% in the adenocarcinomas; and 90% in the large cell undifferentiated carcinoma. The lung tumor that was diagnosed on a needle biopsy specimen showed adenocarcinoma, with 50% of cells having rhabdoid morphology. Among the 4 patients with resected metastatic lesions, the histological diagnosis was large cell undifferentiated carcinoma in 2 patients (with 15% and 90% rhabdoid cells) and sarcomatoid carcinoma in 1 patient (75% rhabdoid cells). The metastases from the fourth patient contained ⬎90% rhabdoid cells. In all 11 cases, the rhabdoid component was characterized by the presence of large cells with abundant eosinophilic cytoplasm, a large eccentric nucleus with a central macronucleolus, and a rounded eosinophilic cytoplasmic inclusion that sometimes caused nuclear indentation (Fig 1).
Salient clinicopathologic features are presented in Table 1. The patients were 7 men and 4 women, who ranged in age from 35 to 70 years (mean age: 56.2 years, median age: 57 years). There was a history of heavy smoking in all 9 patients for whom this information was available. The tumor was located on the left side in 6 patients and on the right side in 5. At presentation, the tumors were staged as follows: TNM stage I, 1 patient; stage III, 3 patients; and stage IV, 6 patients. The tumor stage could not be determined in 1 patient. At initial presentation, 4 patients had metastases beyond the regional lymph nodes. One of these patients had an earlier resection of a lung tumor at another institution, whereas the other 3 had radiological evidence of lung tumor. The most common site for metastases was lymph nodes; this occurred in 6 patients, 4 of whom had metastases to extramediastinal nodal sites. Intrapulmonary metastases were noted radiologically in 3 patients. Other sites of metastases included bone (3 patients), soft tissue (3 patients), brain (2 patients), small intestine (2 patients), and liver (1 patient).
Immunohistochemical Findings The results of immunohistochemical staining are summarized in Table 2. The paranuclear inclusions in the rhabdoid cells stained for pancytokeratin (CK) in 9 of 11 cases and for vimentin in all 11 cases (Fig 2). Cytoplasmic, paranuclear staining for CK7 was seen in 4 of 10 cases. The rhabdoid cells were negative for CK20 in the 10 cases investigated for this marker. No expression for TTF-1 was seen in any of the 11 cases.
Pathological Findings The resected primary tumors were 3.0, 4.0, 4.7, 5.1, and 23 cm in diameter, respectively, in 5 of 6 patients; no information on tumor size was available for the patient who had undergone resection at a different institution. These 5 tumors were described as well circumscribed, with a gray-white to tan-yellow cut surface showing focal areas of hemorrhage and necrosis. Histologically, the primary tumors were sarcomatoid carcinoma in 3 patients, adenocarcinoma in 2 patients, and large cell undifferentiated carcinoma in 1 patient. The proportions of rhabdoid cells in these tumors were 25%, 30%, and 60% in the sarcomatoid carcinomas;
Clinical Outcome Two of our 11 patients were lost to follow-up after the initial visit. For the remaining 9 patients, the follow-up period ranged from 3 to 20 months, with a mean and median of 10 months. Eight of the 9 patients (89%) died of disease, at 3, 3, 4, 5, 10, 11, 15, and 19 months after diagnosis. One patient is alive with no evidence of disease at 20 months. 9
HUMAN PATHOLOGY
Volume 35, No. 1 (January 2004)
logical features and have been shown to have many similarities on immunohistochemical staining.29 The hallmark of rhabdoid cells is a large paranuclear, hyaline, often globular eosinophilic cytoplasmic inclusion that sometimes causes nuclear indentation.1,19 Ultrastructurally, this inclusion is composed of cytoplasmic intermediate filaments that are arranged in a concentric, whorl-like pattern.1,19,22 On occasion, some of these cells have been reported to have variable numbers of dense core-type granules that represent neuroendocrine differentiation.19 A transition between nonrhabdoid and rhabdoid tumor cells has been variably noted,13,19,21 with the rhabdoid cells observed mainly at the periphery of the tumor.21 Most extrarenal rhabdoid tumors show a combined morphology, with the rhabdoid component and an epithelial or mesenchymal component. Wick et al30 proposed the term composite extrarenal rhabdoid tumor for tumors that are composed of both a recognized entity, such as adenocarcinoma, and a population of tumor cells with rhabdoid features. They also suggested that tumors composed exclusively of rhabdoid cells should be labeled malignant extrarenal rhabdoid tumors. In addition, they indicated that because the “rhabdoid” phenotype is seen in a heterogeneous group of lesions of dissimilar histogenesis, this phenotype may represent a “common endpoint of clonal evolution” in tumors of clearly different origins.30 Indeed, most of the cases of lung tumors with rhabdoid features that have been reported in the literature, as well as those that we have studied, have a recognizable “parent” lung carcinoma associated with the rhabdoid cell component. Thus, lung tumors with rhabdoid features seem to fit into the category of composite extrarenal rhabdoid tumor as suggested by Wick et al.30 In our patients, the parent neoplasm was sarcomatoid carcinoma (4 cases), adenocarcinoma (4 cases), and large cell undifferentiated carcinoma (3 cases). Cavazza et al19 suggested that to qualify for such a diagnosis in the lung, rhabdoid cells should comprise ⱖ10% of the tumor cells. This was reiterated by Shimazaki et al,23 who found that tumors with ⬎10% rhabdoid cells behaved more aggressively than did those with ⬍10% rhabdoid cells. Those investigators also found that tumors with ⬍5% rhabdoid cells behaved similarly to large cell carcinoma without rhabdoid cells.23 Only those patients in whom the rhabdoid component of the tumors constituted ⱖ10% of the total tumor are included in this review. On the basis of this criterion, only 21 cases of patients with rhabdoid lung tumors have been published so far.13,19-25 Clinicopathologic features of those 21 patients are summarized in Table 3. The 32 patients (21 previously reported and 11 from the present series) of rhabdoid lung tumors range in age from 25 to 82 years (mean, 56.9 years; median, 57 years). The patients were 20 men and 12 women. The most common presenting symptoms, reported in 23 patients, were respiratory, including cough, hemoptysis, chest pain, hoarseness, and dyspnea. There was a
FIGURE 1. (A) Rhabdoid cells arranged in an alveolar pattern (⫻100). (B) High power showing rhabdoid cells with typical paranuclear cytoplasmic inclusions (⫻400).
DISCUSSION Renal rhabdoid tumor was first described as a distinct clinicopathologic entity occurring in a pediatric population and was characterized by a poor survival rate.1,2 This type of tumor had pure rhabdoid morphology highlighted by the proliferation of typical monotonous rhabdoid cells.28 Since then, extrarenal tumors with rhabdoid morphology have generated much interest and have been described in various other locations such as soft tissue, liver, uterus, skin, brain, prostate, vulva, urinary bladder, orbit, intestine and stomach, tongue, and recently, the lungs.3-17,19-25 Although renal rhabdoid tumors are tumors of childhood, extrarenal rhabdoid tumors are observed in a broad range of age groups.4 Even though rhabdoid tumors of the kidney and extrarenal rhabdoid tumors are considered to be separate entities, the rhabdoid cells have similar morpho10
CARCINOMA OF LUNG WITH RHABDOID FEATURES (Tamboli et al)
TABLE 2. Results of Immunohistochemical Staining Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Case 8
Case 9
Case 10
Case 11
IHC stains
R
NR
R
NR
R
NR
R
NR
R
R
R
NR
R
NR
R
NR
R
NR
R
NR
CK CK7 CK20 TTF-1 Vimentin
⫹, F ⫺ ⫺ ⫺ ⫹
⫹, F ⫺ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹, F ⫹
⫹ ⫹ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹ ⫹, F
⫹ ⫹ ⫺ ⫺ ⫹, F
⫹ ⫹ ⫺ ⫺ ⫹, F
⫹ ⫺ ⫺ ⫺ ⫹
⫹, F ⫺ ⫺ ⫺ ⫹
⫺ ⫺ ⫺ ⫺ ⫹
⫺ ⫺ ⫺ ⫺ ⫹, F
⫹ ND ND ⫺ ⫹, F
⫹ ND ND ⫹ ⫺
⫺ ⫺ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹, F ⫹, F
⫹ ⫺ ⫺ ⫺ ⫹
⫹ ⫺ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫺ ⫹
⫹ ⫹ ⫺ ⫹, F ⫺
Abbreviations: CK, pancytokeratin; CK7, cytokeratin 7; CK20, cytokeratin 20; F, focally; IHC, immunohistochemical; ND, not done; NR, nonrhabdoid; R, rhabdoid; TTF-1, thyroid transcription factor-1.
These findings seem to indicate that CK7 and TTF-1 are of limited value in determining the site of origin of an extrarenal rhabdoid tumor. Therefore, clinical and radiological data are required to exclude a primary tumor located elsewhere, before a diagnosis of a tumor with rhabdoid features is considered to be a lung primary. These tumors have also been variably reported to show neuroendocrine differentiation.19,21,23,29 Thus, there are reports of combined large cell neuroendocrine carcinoma with rhabdoid cells.20 In addition, Leu-7 and glial fibrillary acidic protein have been reported to be positive in a few cases.19 These tumors may be considered to be aggressive, as the majority present with high-stage disease. Among the 17 patients (including 10 of our patients) for whom data on tumor TNM stage were available, 2 presented with stage I disease, 9 with stage III disease, and 6 with stage IV disease. Information on the site of the metastases was available in 20 patients, with the lymph node being the most common site of metastases. The clinical follow-up on these 32 cases ranged from 22 days to 60 months, with a mean of 8.3 months. Nineteen of the 32 (60%) patients died of disease, with survival time ranging from 0.6 to 36 months (mean survival of 8.1 months, median of 5 months). Three were alive with disease, and 3 were alive with no evidence of disease. Two other patients were alive, but their status was not known. One patient died of other causes. No information was available for 1 patient, and the remaining 3 patients were lost to follow-up. Clearly these tumors behave aggressively; however, it is not certain whether these patients do worse than TNM stage–matched patients who have advanced non–small cell lung carcinoma. Comparing the survival rates for cases of rhabdoid lung tumors and historic cases of advanced-stage non–small cell lung carcinoma is also difficult because of the heterogeneity of the study population and the variation in survival rates of patients with advanced non–small cell lung carcinoma (10% to 40% 1-year survival). Also, in keeping with the purported aggressive nature of these tumors, Miyagi et al21 have reported strong positive staining for proliferating cell nuclear antigen in the rhabdoid cells (⬎60%), in contrast to scattered staining in the nonrhabdoid component of the tumor, showing that the rhabdoid cells are highly proliferative.
history of heavy smoking in 19 of the 24 patients for whom this information was available. The size of the primary tumor (reported in 23 patients) ranged from 2.0 cm to 23.0 cm (mean, 7.0 cm). Eighteen tumors occurred on the right side and 14, on the left. The amount of the rhabdoid component of the tumors ranged from 10% to 90% and was associated with 12 cases of adenocarcinoma, 7 cases of large cell undifferentiated carcinoma, 4 cases of sarcomatoid carcinoma, 4 cases of poorly differentiated carcinoma, 3 cases of large cell neuroendocrine carcinoma, and 1 case of sarcoma; 1 case was reported as an extrarenal rhabdoid tumor occurring in the lung, with no mention of an associated parent tumor. It should be noted that almost all of these tumors have been reported to be carcinomas, with the exception of 1 case with sarcomalike features that was reported by Cavazza et al.19 These tumors usually express both vimentin and epithelial markers (CK or epithelial membrane antigen),13,19-21,23,25 although a few tumors that do not express epithelial markers have been reported.19,22,24 Although all the cases in our study did stain for vimentin, 2 of the 11 cases showed no reactivity for CK. In 10 of our cases, 4 were positive for CK7, and all 10 were negative for CK20. All 11 cases were negative for TTF-1.
FIGURE 2. Immunoperoxidase stain for vimentin showing positivity for the cytoplasmic inclusions (⫻400).
11
HUMAN PATHOLOGY
Volume 35, No. 1 (January 2004)
TABLE 3. Summary of Reported Cases of Lung Tumors With Rhabdoid Features
Reference
Sex/age No. (yr)
Symptoms
Location/ Smoking maximum history dimension (cm)
Site of metastases
TNM stage
Associated tumor type
1
F/54
Hemoptysis
Yes
RUL/NA
Lymph node
NA Large cell carcinoma
2 3 4 5 6 7
M/36 M/47 F/71 M/71 F/25 M/74
Chest pain Hemoptysis NA NA Bazex’s syndrome Incidental finding
NA Yes NA NA No Yes
LUL/NA RLL/NA LUL/NA RLL/NA LLL/NA LLL/3.5
NA NA Lymph node NA Lung, lymph node NA
NA NA NA NA NA NA
8 9 10
M/68 F/62 M/40
No Yes No
RML/3 RUL/11 RUL/6
Lymph node Present NA
NA Adenocarcinoma NA LCNEC NA Adenocarcinoma
F/50
Cough and hemoptysis Cough and hemoptysis Cough, chest pain, dyspnea Cough and dyspnea
Yes
LLL/17
Lymph node
12
M/53
Cough and hemoptysis
Yes
LUL/12
NA
Miyagi et al21 13 14 15 16 Shimazaki et al23 17
M/51 M/72 F/50 M/69
Hemoptysis Cough Fatigue Abnormal chest X-ray
Yes No No N/A
RUL/4 RUL/5.6 RML/3.0 RLL/4.5
Lymph node Lymph node NA None
M/66
Hemoptysis
NA
LUL/6.0
None
18
M/82
Yes
LUL/11.0
None
19
F/47
Chest pain, cough, dyspnea Hemoptysis and cough
Yes
RUL/8.5
None
20
F/69
Chest pain
Yes
21
M/59
NA
Yes
NA LCNEC, small cell carcinoma NA LCNEC, small cell carcinoma, SCC IIIA Adenocarcinoma IIIA Adenocarcinoma IA Adenocarcinoma IIIA Poorly differentiated tumor IIIB Poorly differentiated tumor IIIA Poorly differentiated tumor IIIA Poorly differentiated tumor NA Pseudomesotheliomatous adenocarcinoma NA Large cell carcinoma
Cavazza et al19
Rubenchik et al22 Chetty et al13
Chetty et al20 11
Attems and Lintner24 Kaneko et al25
RUL/2.0-cm-thick Duodenum, skin, pleural rind adrenal gland RUL/4.5 Adrenal gland
Sarcoma Adenocarcinoma Adenocarcinoma Large cell carcinoma Large cell carcinoma NA
% Rhabdoid Follow-up cells status (mo) 90
AWD (6)
⬎10 ⬎10 10 ⬎10 10 Most
AWD (4) DOD (4) AWD (2) ASU (5) NA ANED (24)
⬎10 25 ⬎10
DOD (6) DOD (3) LFU (6)
15
DOD (6)
10
DOD (12)
70 90 50 18.2
DOD (36) DOD (4) ASU (41) DOD (1.5)
15.5
DOD (0.6)
15
DOD (1)
60
DOD (10)
NA
Dead, other disease (3) ANED (60)
90
Abbreviations: ANED, alive with no evidence of disease; ASU, alive, status unknown; AWD, alive with disease; DOD, dead of disease; F, female; LCNEC, large cell neuroendocrine carcinoma; LLL, left lower lobe; LUL, left upper lobe; M, male; NA, not available; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe; SCC, squamous cell carcinoma.
A pathologic and immunohistochemical study. Am J Surg Pathol 13:848-858, 1989 8. Carter RL, McCarthy KP, al-Sawm SZ, et al: Malignant rhabdoid tumour of the bladder with immunohistochemical and ultrastructural evidence suggesting histiocytic origin. Histopathology 14: 179-190, 1989 9. Harris M, Eyden BP, Joglekar VM: Rhabdoid tumour of the bladder: A histological, ultrastructural and immunohistochemical study. Histopathology 11:1083-1092, 1987 10. Walford N, Deferrai R, Slater RM, et al: Intraorbital rhabdoid tumour following bilateral retinoblastoma. Histopathology 20: 170-173, 1992 11. Niffenegger JH, Jakobiec FA, Shore JW, et al: Adult extrarenal rhabdoid tumor of the lacrimal gland. Ophthalmology 99:567574, 1992 12. Chetty R, Bhathal PS: Caecal adenocarcinoma with rhabdoid phenotype: An immunohistochemical and ultrastructural analysis. Virchows Arch A Pathol Anat Histopathol 422:179-182, 1993 13. Chetty R, Bhana B, Batitang S, et al: Lung carcinomas composed of rhabdoid cells. Eur J Surg Oncol 23:432-434, 1997 14. Ueyama T, Nagai E, Yao T, et al: Vimentin-positive gastric carcinomas with rhabdoid features. A clinicopathologic and immunohistochemical study. Am J Surg Pathol 17:813-819, 1993 15. Patron M, Palacios J, Rodriguez-Peralto JL, et al: Malignant rhabdoid tumor of the tongue. A case report with immunohistochemical and ultrastructural findings. Oral Surg Oral Med Oral Pathol 65:67-70, 1988 16. Small EJ, Gordon GJ, Dahms BB: Malignant rhabdoid tumor of the heart in an infant. Cancer 55:2850-2853, 1985 17. Batsakis JG, Manning JT: Malignant rhabdoid tumor. Ann Otol Rhinol Laryngol 97:690-691, 1988
In conclusion, lung tumors with rhabdoid cells are uncommon tumors that may behave aggressively. The presence of a rhabdoid component in a lung tumor should be reported, and the clinician should be alerted about the possibly aggressive nature of this tumor. REFERENCES 1. Haas JE, Palmer NF, Weinberg AG, et al: Ultrastructure of malignant rhabdoid tumor of the kidney. A distinctive renal tumor of children. HUM PATHOL 12:646-657, 1981 2. Beckwith JB, Palmer NF: Histopathology and prognosis of Wilms tumors: Results from the First National Wilms’ Tumor Study. Cancer 41:1937-1948, 1978 3. Cattani MG, Viale G, Santini D, et al: Malignant rhabdoid tumour of the uterus: An immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat Histopathol 420:459-462, 1992 4. Parham DM, Weeks DA, Beckwith JB: The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. Am J Surg Pathol 18:1010-1029, 1994 5. Ekfors TO, Aho HJ, Kekomaki M: Malignant rhabdoid tumor of the prostatic region. Immunohistological and ultrastructural evidence for epithelial origin. Virchows Arch A Pathol Anat Histopathol 406:381-388, 1985 6. Matias C, Nunes JF, Vicente LF, et al: Primary malignant rhabdoid tumour of the vulva. Histopathology 17:576-578, 1990 7. Perrone T, Swanson PE, Twiggs L, et al: Malignant rhabdoid tumor of the vulva: Is distinction from epithelioid sarcoma possible?
12
CARCINOMA OF LUNG WITH RHABDOID FEATURES (Tamboli et al) 18. Colby TV, Koss MN, Travis WD: Carcinoid and other neuroendocrine tumors, in Travis WD (ed): Tumors of the Lower Respiratory Tract. Washington, DC, Armed Forces Institute of Pathology, 1995, p 311 19. Cavazza A, Colby TV, Tsokos M, et al: Lung tumors with a rhabdoid phenotype. Am J Clin Pathol 105:182-188, 1996 20. Chetty R: Combined large cell neuroendocrine, small cell and squamous carcinomas of the lung with rhabdoid cells. Pathology 32:209-212, 2000 21. Miyagi J, Tsuhako K, Kinjo T, et al: Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma. Histopathology 37:37-44, 2000 22. Rubenchik I, Dardick I, Auger M: Cytopathology and ultrastructure of primary rhabdoid tumor of lung. Ultrastruct Pathol 20:355-360, 1996 23. Shimazaki H, Aida S, Sato M, et al: Lung carcinoma with rhabdoid cells: A clinicopathological study and survival analysis of 14 cases. Histopathology 38:425-434, 2001 24. Attems JH, Lintner F: Pseudomesotheliomatous adenocarci-
noma of the lung with rhabdoid features. Pathol Res Pract 197:841846, 2001 25. Kaneko T, Honda T, Fukushima M, et al: Large cell carcinoma of the lung with a rhabdoid phenotype. Pathol Int 52:643-647, 2002 26. Travis WD, Colby TV, Corrin B, et al: Histological Typing of Lung and Pleural Tumours. New York, Springer-Verlag, 1999, pp 40-42 27. Sobin LH, Wittekind C: Lung, in Sobin LH, Wittekind C (eds): TNM: Classification of Malignant Tumours (ed 5). New York, Wiley-Liss, 1997, pp 93-97 28. Weeks DA, Beckwith JB, Mierau GW, et al: Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms’ Tumor Study Pathology Center. Am J Surg Pathol 13:439-458, 1989 29. Kaiserling E, Ruck P, Handgretinger R, et al: Immunohistochemical and cytogenetic findings in malignant rhabdoid tumor. Gen Diagn Pathol 141:327-337, 1996 30. Wick MR, Ritter JH, Dehner LP: Malignant rhabdoid tumors: A clinicopathologic review and conceptual discussion. Semin Diagn Pathol 12:233-248, 1995
13