|Year : 2015 | Volume
| Issue : 3 | Page : 657
Large cell lung carcinoma with rhabdoid phenotype: Report of a rare entity presenting with chest wall involvement
Shalini Bahadur1, Mukta Pujani1, Sujata Jetley1, Shaan Khetrapal1, Prabhat Kumar Raina2
1 Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India
2 Department of Surgery, Hamdard Institute of Medical Sciences and Research, New Delhi, India
|Date of Web Publication||9-Oct-2015|
Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi
Source of Support: None, Conflict of Interest: None
Large cell lung carcinoma (LCLC), rhabdoid phenotype (RP) is a rare entity, accounting for 0.1-1% of all lung tumors. It is characterized by presence of more than 10% cells with rhabdoid morphology-large cells with abundant cytoplasm, eccentric nuclei, prominent nucleoli and eosinophilic cytoplasmic inclusions. We report a case of rhabdoid variant of large cell carcinoma in a 65-year-old female. Patient presented with a lump in the right axilla. Computed tomography showed a large mass lesion in right lung with involvement of the chest wall. Tru-cut biopsy from the lung lesion was performed and histopathology was compatible with LCLC. A RP was considered due to the presence of tumor cells with eosinophilic cytoplasmic globules and eccentric nuclei. Cytokeratin and vimentin were diffusely positive while thyroid transcription factor was focally positive. INI-1, desmin, calretinin, HMB-45, and neuroendocrine markers were negative. This case highlights that recognition of large cell carcinoma lung, RP is very important because of its aggressive nature and adverse outcome.
Keywords: Large cell carcinoma, lung, rhabdoid type
|How to cite this article:|
Bahadur S, Pujani M, Jetley S, Khetrapal S, Raina PK. Large cell lung carcinoma with rhabdoid phenotype: Report of a rare entity presenting with chest wall involvement. J Can Res Ther 2015;11:657
|How to cite this URL:|
Bahadur S, Pujani M, Jetley S, Khetrapal S, Raina PK. Large cell lung carcinoma with rhabdoid phenotype: Report of a rare entity presenting with chest wall involvement. J Can Res Ther [serial online] 2015 [cited 2020 Feb 27];11:657. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/657/138039
| > Introduction|| |
Large cell lung carcinomas (LCLC) constitute 10% of all lung cancers. Of these, the rhabdoid phenotype (RP) is a rare histological and clinical entity. Its biological and histological features have not been fully characterized. As a variant, large cell carcinoma with rhabdoid morphology was included in the 1999 WHO classification of lung tumors.  LCLC with RP account for 0.1-1% of all lung malignancies. , A minimum of 10% rhabdoid cell component is required for diagnosis of LCLC-RP. Rhabdoid cells are classically described as large cells with abundant cytoplasm, eccentric nuclei and prominent nucleoli with eosinophilic cytoplasmic inclusions.
RP has been classically described in renal tumors. These tumors behave aggressively and are associated with rapid downhill clinical course. Hence, their identification and recognition is of great importance.
| > Case report|| |
A 65-year-old female presented with pain and swelling in the right axilla with history of pain radiating to back associated with episodic cough. There was no fever, weight loss or hemoptysis. She was a non-smoker. Local examination of right axilla revealed a tender mass fixed to chest wall. No ipsilateral or contralateral lymph nodes or breast lumps were palpable. On chest auscultation breath sounds were absent in right upper chest anteriorly and scapular region posteriorly. Patient's hemogram, liver function tests, renal function tests, and coagulation profile were within normal limits. A chest roentogram showed large round opacity in right upper lobe, extending beyond chest wall, destroying second/third overlying ribs.
Fine-needle aspiration cytology of axillary mass was reported as metastatic adenocarcinoma. To search for a primary, contrast enhanced computed tomography was advised, which showed a 9 × 8.5 × 7.8 cm mass lesion in right upper lobe involving chest wall with lytic destruction of first, second, third rib and ground glass opacity in right upper and middle lobe [Figure 1]. There was mediastinal lymphadenopathy. No mass lesions or lymphadenopathy were detectable in abdomen. A Tru-cut biopsy was performed from the lesion in upper lobe of right lung.
|Figure 1: Computed tomographic axial scan of thorax showing mass lesion in upper lobe, right lung with right chest wall involvement|
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Hematoxylin and eosin stained sections showed a cellular, pleomorphic tumor with polygonal to spindle shaped cells in sheets bearing moderate to abundant eosinophilic cytoplasm, large eccentric to central nuclei showing a prominent eosinophilic nucleoli along with few bizarre multinucleated cells [Figure 2]. Few of the tumor cells showed globular eosinophilic inclusions in cytoplasm adjacent to nucleus [Figure 3]. These cells constituted approximately 10% of tumor cells. A possibility of large cell carcinoma lung was suggested and immunohistochemistry for cytokeratin (CK), vimentin, desmin, synaptophysin, calretinin, and thyroid transcription factor (TTF-1) was advised to confirm a LCLC-RP as well as to exclude primary rhabdomyosarcoma and malignant mesothelioma. CK and vimentin were diffusely positive while TTF-1 positivity was seen focally. Desmin, synaptophysin, and calretinin were uniformly negative [Figure 4]. Clinical background coupled with histomorphology and immunohistochemistry helped us reach a final diagnosis of locally advanced LCLC-RP with a clinical stage of T3N2M0. Neo-adjuvant chemotherapy with pemetrexed and cisplatin was started.
|Figure 2: Photomicrograph showing large pleomorphic tumor cells with few bizarre multinucleated cells (marked by arrow) (H and E, ×400)|
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|Figure 3: Photomicrograph showing rhabdoid cell with globular, eosinophilic cytoplasmic inclusion (marked by arrow) (H and E, ×1000)|
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|Figure 4: Photomicrograph showing immunohistochemistry results-cytokeratin and vimentin were diffusely positive, thyroid transcription factor positivity was focal while desmin was negative|
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| > Discussion|| |
Large cell carcinoma lung has an estimated incidence of approximately 10%; with 0.1-1% of these developing a RP. , Shimazaki et al. on the basis of number of rhabdoid cells, divided LCLC into three types namely, lung tumor with a RP (composed of at least 10% rhabdoid cells), lung carcinoma with small number of rhabdoid cells (<10%) and large cell carcinoma containing no rhabdoid cells.  The present case had approximately 10% rhabdoid cells. Cavazza et al. also advocated the same diagnostic criterion for lung tumor with RP.  Tamboli et al. proposed that a higher percentage of rhabdoid cells, that is 10-90%, should be present to label the tumor as LCLC-RP.  Miyagi et al. in their study have reported three cases of primary lung rhabdoid tumor with a high percentage of tumor being composed of cells with rhabdoid morphology (approximately 50-90%).  LCLC-RP are aggressive tumors and present in middle aged to elderly adults.
The RP is so named due to presence of characteristic rhabdoid cells which were first described in kidney by Beckwith and Palmer.  There appearance is akin to cells of rhabdomyosarcoma whereby polygonal cells with abundant cytoplasm, eccentric nucleus, bearing prominent nucleoli and eosinophilic cytoplasmic inclusions are seen. Ultrastructurally, the inclusions comprise of cytoplasmic intermediate filaments arranged in concentric whorls.
Extra renal rhabdoid tumors have been documented in liver, brain, skin, mediastinum, and soft-tissue.  Wick et al.  in a review put forth the term "composite extra renal rhabdoid tumor" and suggested that tumor showing rhabdoid morphology are a heterogenous group of lesions having dissimilar histogenesis and different lineages of differentiation. As rhabdoid tumors from kidney or of extra renal location can metastasize to lung, diagnosis of primary rhabdoid tumor of lung can be rendered only if radiologic investigations coupled with clinical and pathological findings exclude a primary elsewhere. ,
The LCLC is the most common lung tumor from which RP evolves.  Other histologic variants of lung cancer known to progress to RP are mucinous adenocarcinoma, sarcomatoid carcinoma, squamous cell carcinoma, combined large neuroendocrine and small cell lung carcinoma, malignant melanoma and rhabdomyosarcoma. 
LCLC-RP expresses CK, epithelial membrane antigen and vimentin consistently. Neuroendocrine markers such as neuron-specific enolase, synaptophysin, and chromogranin have known to be expressed variably. ,,,,,, Moreover, INI-1 is consistently negative in all extrarenal rhabdoid tumors.
In present case, strong diffuse positivity was noted with CK and vimentin, while TTF-1 showed only focal positivity. INI-1, desmin, calretinin, and HMB-45 were negative as were markers for neuroendocrine differentiation. LCLC-RP is considered an aggressive tumor with dismal prognosis. ,, The aggressive nature of this tumor is demonstrated by its propensity to metastasize early through lymphatics to regional lymph nodes and widely to liver, intestine, skin, brain and bone by hematogenous route. ,, In the index case also patient had developed axillary and chest wall metastasis at the time of presentation.
| > Conclusion|| |
Rhabdoid tumor of lung is a rare entity with aggressive biological behavior often presenting in advanced stage. Therefore, importance lies in early recognition, timely aggressive management and a multi-modality approach for long-term survival and disease control.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]