|Year : 2020 | Volume
| Issue : 1 | Page : 102-104
Gestational pulmonary giant cell carcinoma - An autopsy report
Rushabh Shah, Pradeep Vaideeswar, Tasneem Cochin
Cardiovascular and Thoracic Division, Department of Pathology, Seth GS Medical College, Mumbai, Maharashtra, India
|Date of Submission||09-Aug-2018|
|Date of Decision||03-Sep-2018|
|Date of Acceptance||04-Sep-2018|
|Date of Web Publication||26-Feb-2020|
Cardiovascular and Thoracic Division, Department of Pathology, Seth GS Medical College, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Cancer is an uncommon event in pregnancy. The most common gestational cancers arise from the breast and cervix. Although lung cancer is the most common malignancy, its occurrence in pregnancy is a distinctly rare event. Diagnosing it during pregnancy is an additional challenge as the pregnancy, common respiratory ailments, and the lung cancer can have overlapping symptoms. We report an uncommon histological variant of lung cancer – giant cell carcinoma, which resulted in a fatal outcome in a 26-year-old pregnant woman. A high level of suspicion and vigilance should be exercised during pregnancy to diagnose such rarer entities.
Keywords: Gestational cancers, giant cell carcinoma, pregnancy, pulmonary carcinoma
|How to cite this article:|
Shah R, Vaideeswar P, Cochin T. Gestational pulmonary giant cell carcinoma - An autopsy report. Indian J Cancer 2020;57:102-4
| » Introduction|| |
Cancer during pregnancy is uncommon but not rare, with worldwide epidemiological variation and overall incidence of approximately 1 in 1000 pregnancies or 0.07%–0.1%. Such gestational cancers, which can also occur in the postpartum period, have a lower incidence in developing countries because of the younger age of conception. However, in the developed world, there is a rising trend of gestational cancer to child-bearing at an older age, and this coincides with the age at which cancers develop in women of reproductive age. It follows that even in pregnancy, most cancers diagnosed are mammary and cervical carcinomas, accounting for nearly half the cases. Although the first case of lung cancer in pregnancy in the English literature was reported in 1953, the association is distinctly rare. We report an uncommon histological variant of giant cell carcinoma during pregnancy that lead to a fatal outcome in a young pregnant woman.
| » Case Report|| |
A 26-year-old woman with 31 weeks of gestation was a known case of hypothyroidism on regular medications for the past 2 years. Five months ago, she had low-to-moderate grade fever and cough with scanty mucoid expectoration. After 3 months, a diagnosis of sputum-negative pulmonary tuberculosis was made on the basis of an ill-defined consolidation in the right upper and mid-zone features. Antitubercular therapy was started with some improvement for the next 27 days. But she became symptomatic for 5 days with complaints of high-grade fever, retrosternal burning chest pain, nonexertional dyspnea, and reduced fetal movements and was admitted in our tertiary-care hospital. On examination, she was in poor general condition with fever (104° F), tachycardia (feeble, thready pulse rate of 108/min), hypotension (blood pressure of 90/60 mm Hg), bilateral pedal edema, and altered sensorium. On chest auscultation, there was reduced air entry on the right side with bilateral lung crepitations; heart sounds were normal. The uterus was 28–30 weeks in size and relaxed. Fetal heart sounds were audible and regular. The patient was irritable with incoherent speech and occasionally obeying simple commands. Her hematological investigations were as follows: hemoglobin 100 g/L, total leukocyte count 48.6 × 109/L, and platelet count of 609 × 109/L. The peripheral smear revealed 90% neutrophils in the differential count with toxic granules and presence of few myelocytes, metamyelocytes, and band forms. The erythrocyte sedimentation rate was 95 mm after 1 h. The results of the coagulation profile were as follows: fibrinogen 441 mg/dL (normal 200–400 mg/dL), fibrin degradation products >320 μg/mL (normal <5 μg/mL), and D-dimer 3.3 mg/dL (normal <0.3 mg/dL). The clinical diagnosis was septicemia with oligohydramnios and intrauterine growth retardation. Since no active obstetric management was required, supportive treatment was started for stabilization. However, her condition continued to deteriorate and she succumbed within 10 hours after admission.
At autopsy, both lungs were of normal size and shape. There was bilateral patchy pleural opacification with multiple large and small bulging, pale yellow subpleural nodules [Figure 1]a. The lungs on cut surface showed such nodules distributed all over in the parenchyma, ranging in sizes from 0.5 to 3 cm in diameter [Figure 1]b. All were well-circumscribed with a creamy granular cut surfaces. All the nodules showed classic features of giant cell carcinoma. There were sheets or clusters of uninucleated and multinucleated giant cells embedded in connective tissue, which was heavily infiltrated by neutrophils [Figure 1]c and [Figure 1]d. The uninucleated cells were largely polygonal with moderate to abundant eosinophilic cytoplasm with pleomorphic vesicular nuclei and prominent nucleoli, whereas the multinucleated cells had two to six pleomorphic nuclei. Some showed eosinophilic large nucleoli. A striking feature was the presence of emperipolesis, wherein the cytoplasm showed many “engulfed” neutrophils [Figure 1]e. The cells were positive for CK 7 and CK 19 [Figure 2]; TTF 1 was negative.
|Figure 1: The left lung showing multiple well-circumscribed pale yellow nodules as seen on the (a) external and (b) cut surfaces. The nodules were largely composed of giant cells, which were (c) uninucleated (H and E ×400) or (d) multinucleated (arrow). The background shows large numbers of neutrophils (H and E ×400); (e) note the presence of prominent emperipolesis (arrow, H and E ×400)|
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|Figure 2: Immunohistochemical staining showing positivity for (a) CK 7 (×250) and (b) CK 19 (×400)|
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The anterior segment of the right upper lobe showed an irregular cavitatory lesion [3 × 2.5 × 2 cm, [Figure 3]a with granular, yellowish white shaggy lining. Interestingly, the wall of the irregular cavity in the right upper lobe was thick and white, which showed an adenocarcinoma in a sclerotic background. Peripherally, there was a lepidic pattern [Figure 3]b with psammoma bodies. Another cavity (4 × 3 × 2.5 cm) traversed by trabeculae was present in the apical segment of the right lower lobe. The carinal lymph node was enlarged (3 cm in diameter) with peripheral anthracosis and predominant yellowish white granular appearance due to metastatic tumor. No other tumor (primary or metastatic) was found anywhere at autopsy.
|Figure 3: (a) The cut surface of the right lung showing presence of irregular cavities. The arrow points to the whitish thickened wall that on histology revealed (b) adenocarcinoma with focal lepidic pattern (H and E ×400)|
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| » Discussion|| |
We have reported a rare variant of lung cancer, giant cell carcinoma, in a young pregnant woman. The carcinoma had produced fever and had elicited a neutrophilic leukemoid reaction, leading to a mistaken diagnosis of sepsis. Although overall lung cancer is one of the most common malignancies, those occurring in the gestational period are distinctly uncommon. Due to paucity of data with reference to gestational lung cancer, the exact incidence is not known. In a very recent review by Bellido et al., less than 70 pathologically confirmed cases have been reported. The median age of the patient is 36 years with a median gestational age of 27.3 months; nearly half of these pregnant women have had a positive history of smoking., There may also be additional genetic and environmental factors that would play a role in carcinogenesis. Furthermore, higher amount of circulating estrogen and accompanying immunomodulation are conducive to cancer growth, which would explain the aggressive proliferation and early dissemination. It is not surprising to note that a majority of the patients have advanced stages of disease. Adenocarcinoma is the most common histological type., Our patient was a nonsmoker and only 26-year-old. She had multiple nodules that essentially showed classic histomorphology of giant cell carcinoma, which is rarer variant of the rare pulmonary sarcomatoid carcinoma. Uninucleated and multinucleated atypical giant cells in an inflammatory background with prominent emperipolesis were observed. The larger irregular nodular area in the right upper lobe showed a focus of lepidic adenocarcinoma, being overwhelmed by the giant cells. Molecular markers could not be performed due to financial constraints.
Gestational lung cancers present diagnostic and therapeutic challenges., There is often low level of clinical suspicion and misinterpretation as well, since both the physician and the patient might consider cancer-related nonspecific symptoms to be pregnancy-related. There is also overlapping clinical presentation with respiratory ailments such as pulmonary tuberculosis, which was the case in this patient. In addition, we often face a problem of diagnostic delay due to limited use of imaging modalities. Interestingly, the dilemma in our patient was further compounded by the development of acute febrile illness with a leukemoid reaction that suggested sepsis and septic shock. The leukocytosis developed as a hematological para-neoplastic syndrome due to the cytokines (granulocyte colony-stimulating factor and interleukin 6) released by the giant cells.
The presence of lung cancer makes pregnancy a high-risk event as the maternal and fetal prognosis is threatened. It should be noted that an accompanying leukemoid reaction worsens the prognosis with a high risk of metastases, which can be present in the placenta or even in the fetus. Our patient had intrapulmonary and carinal lymph nodal metastases. Treatment is difficult and prognosis is dismal since the experience is limited to a restricted number of patients and one has to consider the safety and efficacy of chemoradiation, although there may be a role of targeted therapy in future. Apart from reporting this case of gestational pulmonary giant cell carcinoma, our goal is to also emphasize that one should keep a high level of suspicion and be vigilant during pregnancy for rarer entities so as to avoid fatalities.
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.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Mitrou S, Zarkavelis G, Fotopoulos G, Petrakis D, Pavlidis N. A mini review on pregnant mothers with cancer: A paradoxical coexistence. J Adv Res 2016;7:559–63.
Ji YI, Kim KT. Gynecologic malignancy in pregnancy. Obstet Gynecol Sci 2013;56:289–300.
Barr JS. Placenta metastases from a bronchial carcinoma. J Obstet Gynaecol Br Emp 1953;601: 895–7.
Bellido C, Barbero P, Forcén L, Blanco M, Alonso-Riaño M, Galindo A. Lung adenocarcinoma during pregnancy: Clinical case and literature review. J Matern Fetal Neonatal Med 2018;18:1-3.
Holtan SG, Creedon DJ, Haluska P, Markovic SN. Cancer and pregnancy: Parallels in growth, invasion, and immune modulation and implications for cancer therapeutic agents. Mayo Clin Proc 2009;84:985–1000.
Li X, Zhang Z, Liu J, Wang D, Wei S, Chen J. Molecular features of giant-cell carcinoma of the lung: A case report and literature review. Onco Targ Ther 2018;11:751–6.
Wang D, Zhang H, Yu F, Fang B. Extreme leukocytosis and leukemoid reaction associated with the lung sarcomatoid carcinoma: An unusual case report. Int J Gen Med 2017;10:7–9.
[Figure 1], [Figure 2], [Figure 3]