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Coughing up: “Adenosquamous carcinoma lung with unusual initial presentation as an ulceroproliferative growth” – case report and review of literature


1 Department of Cancer Surgery, VMMC and Safdarjung Hospital, New Delhi, India
2 Department of Radiotherapy, VMMC and Safdarjung Hospital, New Delhi, India
3 Department of Pathology, VMMC and Safdarjung Hospital, New Delhi, India

Correspondence Address:
Gunjesh Kumar Singh,
Department of Radiotherapy, VMMC and Safdarjung Hospital, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_694_17

 > Abstract 


Lung carcinoma is the most common carcinoma seen in males with the skin being a rare metastatic site. Adenosquamous carcinoma as a rare histologic subtype, showing cutaneous metastasis is an unusual event with no reports in the literature till date. Skin metastasis is an alarming sign, carries poor prognosis, and is associated with shortened survival. Herein, we report a case of 60-year-old male who presented with isolated cutaneous metastasis as a chronic nonhealing ulcer over the sternal region for 3 years (unusual) in the first place, without any other associated symptoms and clinical evidence of the primary. Wide local excision of the lesion was performed after proper workup which revealed metastatic adenosquamous carcinoma. The patient was advised systemic chemotherapy. A high index of suspicion along with clinico-radio-pathological correlation in these cases is of utmost importance and forms the basis of accurate diagnosis.

Keywords: Adenosquamous carcinoma of the lung, cutaneous metastasis, ulcer



How to cite this URL:
Kumar R, Singh GK, Singh P. Coughing up: “Adenosquamous carcinoma lung with unusual initial presentation as an ulceroproliferative growth” – case report and review of literature. J Can Res Ther [Epub ahead of print] [cited 2019 Jul 18]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=257927




 > Introduction Top


Lung carcinoma is one of the most common malignancies seen worldwide. It is the most common carcinoma in males and stands fourth in females.[1] Adenocarcinoma followed by squamous cell carcinoma, small cell carcinoma, and large cell carcinoma are the common histological subtypes. Adenosquamous carcinoma is a rare histological subtype of non-small cell carcinoma of the lung, which accounts for about 0.4% to 4% of cases.[2] Hilar lymph nodes, adrenal gland, bone, brain, and liver are the common sites of metastasis.[3] Cutaneous metastasis is rarely encountered in lung carcinoma, with an incidence range of 1%–12%.[4],[5] It may even be the presenting clinical feature and carries poor prognosis.[3] We report a rare case of cutaneous metastasis from adenosquamous carcinoma lung in a 60-year-old male who initially presented with a solitary ulcer over the sternal region for 3 years. According to the English literature, cutaneous metastasis from the same has not been reported so far.


 > Case Report Top


A 60-year-old male, a chronic smoker, presented to us with an ulcer over anterior chest wall in the region of sternum for 3 years. His general physical examination was unremarkable with the Eastern Cooperative Oncology Group Performance Status 1. On local examination, there was a solitary ulceroproliferative growth (UPG) of size 4 cm × 3 cm × 2 cm over the sternal region [Figure 1]. It had well-defined margins with an irregular surface covered with purulent discharge. It was nontender, firm-to-hard in consistency, and showing restricted mobility. Biopsy from the lesion showed features of adenosquamous carcinoma with tumor cells showing positivity for thyroid transcription factor (TTF)-1, mucin-1 (MUC-1), p63, and cytokeratin (CK), suggesting possible primary in the lung [Figure 2]a,[Figure 2]b, [Figure 2]c, [Figure 2]d. Mutational analysis was done outside. The tumor cells were negative for epidermal growth factor receptor, KRAS, and anaplastic lymphoma kinase mutation. Contrast-enhanced computed tomography (CECT) thorax and abdomen showed a heterogeneously enhancing mass lesion measuring 2.9 cm × 2.8 cm in subcutaneous region at the level of manubrium sterni and a heterogeneously enhancing nodule measuring 1.7 cm × 1.7 cm with speculated margins in the right upper lobe of the lung, respectively [Figure 3]a and [Figure 2]b. In view of the clinical, radiological, and histopathological features, a diagnosis of cutaneous metastasis from adenosquamous carcinoma lung was made. The patient underwent wide local excision of the solitary UPG with split-thickness grafting. Peroperatively, a solitary UPG measuring about 4 cm × 3 cm was present over the presternal area, involving the skin and the subcutaneous tissue, which on histopathological examination showed similar morphology and immunohistochemical (IHC) pattern. The underlying muscle and the sternal periosteum were free of tumor. After discussion in the multidisciplinary clinic, the patient has been advised chemotherapy with paclitaxel and carboplatin.
Figured 1: Ulceroproliferative growth over sternal area

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Figure 2: (a) Dermis shows tumor cells arranged in clusters and sheets. The cells have moderate eosinophilic cytoplasm, vesicular nuclei, and small nucleoli (H and E: ×10), (b-d) immunohistochemical showing positivity for thyroid transcription factor-1, mucin-1, and p63, respectively

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Figure 3: (a) Contrast-enhanced computed tomography thorax: (Arrow) – heterogeneously enhancing mass lesion measuring in subcutaneous region at the level of manubrium sterni and (b) contrast-enhanced computed tomography thorax: (Arrow) – heterogeneously enhancing nodule with speculated margin in the right upper lobe of the lung

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 > Discussion Top


Cutaneous metastasis accounts for 0.6%–1.4% of all visceral metastasis and is seen in 0.7%–0.9% of patients with malignancies.[6],[7] It may even be the first manifestation of an internal disease.[7] Cutaneous metastasis from lung carcinoma is a rare occurrence with only a handful of cases reported in the literature.[8]

Cutaneous metastasis from lung carcinoma

Incidence

The malignancies commonly seen associated with cutaneous metastasis differ in males and females. Malignant melanoma, lung carcinoma, and colorectal carcinoma are the common sources in males, whereas it has been reported most frequently with breast carcinoma, colorectal carcinoma, and malignant melanoma in case of females.[9],[10] About 1%–12% of patients with carcinoma lung have been reported developing cutaneous metastasis;[3],[5] however, the same, according to the Lookingbill et al., is 11.8% for males and 2% for females.[9] Lung carcinoma is known to be the fastest malignancy showing cutaneous involvement after the initial diagnosis with an average period of 5.75 months.[11]

Clinical features

The metastatic skin lesion can be asymptomatic or may be associated with pain and tenderness. Timely diagnosis requires a high index of suspicion in these cases, especially when the presentation is chronic as an idiopathic nonhealing ulcer. The metastatic skin lesions do not have characteristic appearances. They may present as rapidly growing dermal or subcutaneous nodules, macules, infiltrated or indurated plaques, discoid lesions, tumor nodules with telangiectasias, bullous/papulosquamous lesions, scarred plaques, or ulcers simulating primary cutaneous pathology with frequent clinical misdiagnoses.[3],[12] The skin over the anterior chest wall, abdominal wall, and head-and-neck region are the usual metastatic sites reported.[5]

Histopathological correlation

Cutaneous metastasis may develop from all histological subtypes of lung carcinoma.[13]

Some studies quote adenocarcinoma as the most common subtype showing this phenomenon.[5],[14],[15] Others state that large cell carcinoma has the highest incidence followed by adenocarcinoma.[16],[17] Mesothelioma, carcinoid tumors of the lung, mucoepidermoid carcinoma, pulmonary sarcoma, intravascular bronchoalveolar tumor, well-differentiated fetal adenocarcinoma, and adenoid cystic carcinoma are the other rare histologies in which cutaneous metastases have been described.[5] Adenosquamous carcinoma is in itself a rare malignant lung tumor which is defined as a carcinoma showing components of both adenocarcinoma and squamous cell carcinoma, with each comprising at least 10% of the tumor. The prognosis is dismal as compared to adenocarcinoma and squamous cell carcinoma.[2] Till date, cutaneous metastasis from adenosquamous carcinoma lung has not been reported in the literature, and hence, ours is the first.

IHC remains crucial in the determination of the site of the primary tumor. The simultaneous evaluation of TTF-1, p63, and CK7/CK20 is necessary in suspected primary in the lungs.[5] The metastatic skin lesion from primary adenosquamous carcinoma lung usually shows positivity for TTF-1, MUC-1, p63, CK7, and negative expression for CK20. The closest differential diagnosis is primary cutaneous adenosquamous carcinoma which can be ruled out with the help of IHC profile, that is, p63, CK7, carcinoembryonic antigen, carbohydrate antigen 19-9 positive, and TTF-1 negative as well as imaging studies.

In general, cutaneous metastasis from any primary can be diagnosed with the help of clinical, radiological, and histopathological examination with IHC being an important and helpful adjunct. Radiology includes imaging studies with CECT, magnetic resonance imaging, and whole-body positron emission tomography.

Metastatic spread to the skin from lung carcinoma is a poor prognostic sign with a reported mean survival period of 5–6 months and is associated with an aggressive course.[3],[5] Whereas, in contrast, our patient unusually presented primarily with a metastatic disease in the form of an ulcer (which progressed to UPG) over the sternal area for about 3 years without any accompanying symptoms of lung disease. The pathological workup gave a suspicion of primary in the lungs which followed by radiological examination, helped us reach a definitive diagnosis.

The treatment of solitary cutaneous metastasis includes either surgical resection alone or in combination with chemotherapy and/or radiotherapy. However, chemotherapy is the treatment of choice in case of multiple cutaneous metastases or presence of systemic spread.[5],[18]

Even more, Ambrogi et al. proposed that surgical resection of the solitary cutaneous metastatic lesion may increase the survival of the patient.[18] Radiotherapy emerges out as useful palliative therapy and helps in relieving pain and bleeding.[19]

Through this case report, we intend to highlight and impress on three peculiar features:

  1. The patient, in the first instance, presented with a solitary UPG over the sternal area without accompanying symptomatology of lung carcinoma
  2. Cutaneous metastasis from adenosquamous carcinoma lung is being reported for the first time
  3. Unexpected clinical course – despite being associated with poor prognosis and short survival, the patient is alive with metastatic skin disease for 3 years.



 > Conclusion Top


Cutaneous metastasis is a rare phenomenon and may even be the presenting clinical feature of lung carcinoma. It is often misdiagnosed clinically as benign cutaneous entity (simulating primary skin lesion) due to its varied clinical appearances. Proper history (e.g., history of smoking), adequate clinical, and radiological examination along with histopathological evaluation are the pillars to correct diagnosis. Therefore, in a patient presenting with cutaneous lesion of chronic nonhealing nature, although infrequently seen, cutaneous metastasis should always be in the list of possible differentials even in the absence of symptoms or lesions elsewhere. Reportedly, cutaneous metastasis from the lung carries poor prognosis with a mean survival of only few months; however, in unusual cases, patients may have a prolonged and symptom-free life as in our case. The patient will be followed up curiously to know the treatment response and course of the disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors would like to acknowledge the department of pathology for the commitment and collaboration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
GLOBOCAN -2012 World Cancer Factsheet. Available from: http://gco.irc.fr/today. [Last accessed on 2017 Mar 10].  Back to cited text no. 1
    
2.
Tochigi N, Dacic S, Nikiforova M, Cieply KM, Yousem SA. Adenosquamous carcinoma of the lung: A microdissection study of KRAS and EGFR mutational and amplification status in a western patient population. Am J Clin Pathol 2011;135:783-9.  Back to cited text no. 2
    
3.
Pajaziti L, Hapçiu SR, Dobruna S, Hoxha N, Kurshumliu F, Pajaziti A, et al. Skin metastases from lung cancer: A case report. BMC Res Notes 2015;8:139.  Back to cited text no. 3
    
4.
Hidaka T, Ishii Y, Kitamura S. Clinical features of skin metastasis from lung cancer. Intern Med 1996;35:459-62.  Back to cited text no. 4
    
5.
Mollet TW, Garcia CA, Koester G. Skin metastases from lung cancer. Dermatol Online J 2009;15:1.  Back to cited text no. 5
    
6.
Wong CY, Helm MA, Kalb RE, Helm TN, Zeitouni NC. The presentation, pathology, and current management strategies of cutaneous metastasis. N Am J Med Sci 2013;5:499-504.  Back to cited text no. 6
    
7.
Ardavanis A, Orphanos G, Ioannidis G, Rigatos G. Skin metastases from primary lung cancer. Report of three cases and a brief review. In Vivo 2006;20:671-3.  Back to cited text no. 7
    
8.
Cidon EU. Cutaneous metastases in 42 patients with cancer. Indian J Dermatol Venereol Leprol 2010;76:409-12.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: A retrospective study of 4020 patients. J Am Acad Dermatol 1993;29:228-36.  Back to cited text no. 9
    
10.
Marcoval J, Moreno A, Peyrí J. Cutaneous infiltration by cancer. J Am Acad Dermatol 2007;57:577-80.  Back to cited text no. 10
    
11.
Nashan D, Müller ML, Braun-Falco M, Reichenberger S, Szeimies RM, Bruckner-Tuderman L, et al. Cutaneous metastases of visceral tumours: A review. J Cancer Res Clin Oncol 2009;135:1-4.  Back to cited text no. 11
    
12.
Ambrogi V, Nofroni I, Tonini G, Mineo TC. Skin metastases in lung cancer: Analysis of a 10-year experience. Oncol Rep 2001;8:57-61.  Back to cited text no. 12
    
13.
Brownstein MH, Helwig EB. Metastatic tumors of the skin. Cancer 1972;29:1298-307.  Back to cited text no. 13
    
14.
Connor DH, Taylor HB, Helwig EB. Cutaneous metastases of renal cell carcinoma. Arch Pathol 1963;76:339-46.  Back to cited text no. 14
    
15.
Ahmed I. Cutaneous metastases. In: Bolognia JL, Jorizzo JL, Rapini RP, Horn TD, Mascaro JM, Mancini AJ, et al., editors. Dermatology. Spain: Mosby; 2003. p. 1953-6.  Back to cited text no. 15
    
16.
García-Arpa M, Rodríguez-Vázquez M, Sánchez-Caminero P, Delgado M, Vera E, Romero G, et al. Digital acrometastasis. Actas Dermosifiliogr 2006;97:334-6.  Back to cited text no. 16
    
17.
Hazelrigg DE, Rudolph AH. Inflammatory metastic carcinoma. Carcinoma erysipelatoides. Arch Dermatol 1977;113:69-70.  Back to cited text no. 17
    
18.
Ambrogi V, Tonini G, Mineo TC. Prolonged survival after extracranial metastasectomy from synchronous resectable lung cancer. Ann Surg Oncol 2001;8:663-6.  Back to cited text no. 18
    
19.
Kamble R, Kumar L, Kochupillai V, Sharma A, Sandhoo MS, Mohanti BK, et al. Cutaneous metastases of lung cancer. Postgrad Med J 1995;71:741-3.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

 
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