Table 6.
Previously reported cases of hepatoid large cell carcinoma of the lung (HLCCL)
| No | Author/Year | Centre | Sex/Age | Smoking history (pack-year) | Liver disease and other history | Symptom | Location/Size (cm) | Tumor markers | AJCC 8th Edition Stage | Treatment | Immunohistochemistry | Tumor relapse site | Prognosis/Cause of death | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||||||
| Positive (+) | Negative (-) | |||||||||||||
| 1 | Koizumi, 1979 | Japan | M/63 | N/A | N/A | N/A | N/A | AFP↑ | N/A | C,R | N/A | N/A | N/A | 5 mo dead/N/A |
| 2 | Yokoyama K, 1981 [74] | Japan | M/69 | N/A | N/A | Bloody sputum, fever, cough | RLL/11×11×7 | AFP↑ | pT4N0M1b (IVA) | C, Immuno | AFP, A1AT, A1ACT, CEA | N/A | Kidney, brain (N/A) | 2 mo dead/N/A |
| 3 | Saga, 1983 | Japan | M/64 | N/A | N/A | N/A | N/A | AFP↑ | N/A | C, R | N/A | N/A | N/A | 30 mo dead |
| 4 | Miyake M, 1986 [18] | Japan | M/40 | 23 | History of appendectomy and gastric ulcer, family history of gastric cancer and tuberculosis | Bloody sputum, cough | RUL/8×9×7 | AFP↑, CEA→ | pT4N2M0 (IIIB) | O | AFP | N/A | Peritoneum (8 mo) | 14 mo dead/intraperitoneal metastasis |
| 5 | Sakamoto O, 1987 [75] | Japan | M/72 | 50 | None | Dry cough, weight loss | RLL/8×12 | AFP↑ | cT4N1M0 (IIIA) | C,R | AFP | N/A | No | 4.5 mo dead/cancerous pleurisy and empyema |
| 6 | Yoshimoto T, 1987 [76] | Japan | F/61 | N/A | N/A | Bloody sputum | LUL/N/A | AFP↑, CEA↑, β-hCG↑ | N/A | C | N/A | N/A | brain (6 mo) | 7 mo dead/relapse |
| 7 | Kamishiro, 1987 | Japan | M/73 | N/A | N/A | N/A | N/A | AFP↑ | N/A | C | N/A | N/A | N/A | 19 mo dead/N/A |
| 8 | Taguchi, 1989 | Japan | M/58 | N/A | N/A | / | N/A | AFP↑ | N/A | O, C | N/A | N/A | N/A | 9 mo alive |
| 9 | Okunaka T, 1992 [77] | Japan | M/49 | N/A | N/A | Cough, bloody sputum | RUL/6×5×5 | AFP↑, CA19-9→, CEA→ | pT3N0M0 (IIB) | O | AFP | N/A | No | 11 mo alive |
| 10 | Ohshima, 1992 | Japan | M/55 | N/A | N/A | / | N/A | AFP↑ | N/A | O | N/A | N/A | N/A | N/A |
| 11 | Hayashi A, 1995 [78] | Japan | M/54 | 35 | Family history of gastric cancer, alcohol abuse | Cough, sputum | LML/3.5×2.5 | AFP↑, CEA→, SCC→, CA19-9→, β-hCG→ | pT2aN0M0 (IB) | O | AFP | CEA | N/A | 18 mo alive |
| 12 | Hirabayashi H, 1995 [26] | Japan | M/55 | N/A | Pulmonary tuberculosis, diabetes, chronic hepatitis | None | RLL/5×5 | AFP↑ | pT2bN0M0 (IIA) | O | AFP | N/A | N/A | 132 mo alive |
| 13 | Bessho T, 1996 [79] | Japan | M/81 | 150 | Gastric ulcer surgery | Fatigue | LLL/10×8×5 | AFP↑, TPA↑, IAP↑, NSE↑ | pT4N0M0 (IIIA)* | O | N/A | N/A | No | 10 mo alive |
| 14 | Nasu M, 1997 [80] | Japan | M/63 | N/A | Pleuritis | Bloody sputum, fever | RUL/8 | AFP↑, β-hCG→, CA19-9→, CEA→, PIVKA-II ↑ | cT4N1M1c (IVB) | C | AFP, PIVKA-II, A1AT, A1ACT | CgA | Lung, right adrenal, brain (N/A) | 11 mo dead/bronchopneumonia |
| 15 | Hiroshima K, 2002 [4] | Japan | M/71 | 45 | N/A | Common cold | RLL/10.5×8.5×7 | AFP↑, CA19-9↑, CEA→ | pT4N1M0 (IIIA)** | O, R | AFP, CgA, NCAM, VEGF | Syn, CEA | Brain (5 mo), left lung (6 mo) | 12 mo dead/brain metastasis |
| 16 | Wu ZY, 2007 [7] | China | M/50 | 40 | N/A | Weight loss | RUL/6×5×5 | AFP→, CEA→, NSE→ | cT4N1M0 (IIIA) | O | AFP | HepPar-1, CA199 | No | 45 mo alive |
| 17 | Khozin S, 2012 [9] | USA | F/56 | Yes | N/A | Chest pain, cough, intermittent night sweats, weight loss | RML/5.5&1.8 | AFP→, β-hCG→ | cT4N0M0 (IIIA) | Crizotinib*** | AE1/AE3, CAM5.2, CK7, CK5/6, HepPar-1, Claudin 4, EMA, OCT4, CEA, CD10 | TTF-1, BHCG, CK20, Vim, GCDFP-15, P63, CHG, thyroglobulin, RCC | No | 6 mo alive |
| 18 | Yu JH, 2012 [81] | Korea | M/70 | 50 | N/A | None | LLL/6×5.2 | AFP↑, PIVKA-II↑, CEA→, α-hCG→ | cT3N3M0 (IIIC) | C | N/A | N/A | No | 12 mo dead/lung infection, respiratory failure |
| 19 | Lin SF, 2013 [82] | China | M/66 | 40 | Hepatitis B virus carrier for 30 years, gallbladder polyps, rheumatoid arthritis | Cough | RUL/7.4×6×4.8 | AFP↑, β-hCG→, CEA→, SCC→ | pT4N2M0 (IIIB) | O, C | AE1/AE3, AFP, Gly-3, CEA | CK7, CK20, TTF-1, HepPar-1, CgA, Syn, CD56 | No | 48 mo alive |
Pathology showed HLCCL complicated with squamous cell carcinoma;
Pathology showed large cell neuroendocrine carcinoma;
Gene mutation examination showed EGFR (exons 18-21), KRAS (exons 2, 3), BRAF (exon 15), AKT (exon 1), PIK3CA (exons 9, 20), NRAS (exons 2, 3): Wild type; HER2 rearrangement (46%); ALK (72.8%).
A1AT, α1-antiitrypsin; A1ACT, α1-antichymotrypsin; AFP, α-fetoprotein; ALK, anaplastic lymphoma kinase; β-hCG, beta-human chorionic gonadotropin; BRAF, b-rafproto-oncogene; C, chemotherapy; CD, cluster of differentiation; CEA, carcinoembryonic antigen; CgA, chromogranin A; CK, cytokeratin; EGFR, epidermal growth factor receptor; EMA, epithelial membrane antigen; Gly-3, glypican-3; HepPar-1, hepatocyte paraffin 1; HER2, human epidermal growth factor receptor 2; LLL, left lower lobe; LN, lymph node; LUL, left upper lobe; N/A, not mentioned; NCAM, neural cell adhesion molecule; NSE, neuron-specific enolase; O, operation; P53, protein 53; PD-L1, programmed death ligand 1; R, radiotherapy; RCC, renal cell carcinoma; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe; Syn, synaptophysin; TTF-1, thyroid transcription factor-1; VEGF, vascular endothelial growth factor; Vim, vimentin.