Yusuke Takanashi

Methotrexate-associated lymphoproliferative disorder presenting as extranodal NK/T-cell lymphoma arising in the lungs

Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstein–Barr virus (EBV) sometimes contributes to the development of MTX‐associated LPD. Herein, we report the case of a 64‐year‐old Japanese woman with RA who showed complications of EBV‐positive MTX‐associated LPD. This case is exceedingly rare in that the LPD was confined to the lungs and its subclassification was extranodal NK/T‐cell lymphoma. Only four cases of extranodal NK/T‐cell lymphoma in the setting of MTX‐associated LPD have ever been reported in the English language literature, only one of which was an extranasal NK/T‐cell lymphoma, similar to our case. Extranasal NK/T‐cell lymphomas show more aggressive behavior than nasal NK/T‐cell lymphomas, possibly reflected by the considerable re‐exacerbation of the lesions in only two months after the cessation of MTX in our case. However, the SMILE regimen (steroid, methotrexate, ifosfamide, l‐asparaginase, and etoposide) was able to suppress tumor growth in this case.

ALK Rearrangement in Keratinizing Squamous Cell Lung Carcinoma: Immunohistochemistry of ALK-protein as a Convenient ALK Screening

Fusion of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene has been identified as having a prevalence of approximately 5% in Japanese patients with non-small cell lung cancer (NSCLC), primarily adenocarcinoma [1]. Indeed, ALK-fusion is rarely observed in histologic types of lung cancer other than adenocarcinoma. This fusion gene is commonly seen in a younger age group of never or previous light smokers [2].

ALK‐rearranged squamous cell carcinoma of the lung

The fusion gene echinoderm microtubule‐associated protein‐like 4 (EML4)–anaplastic lymphoma kinase (ALK) is identified in approximately 5% of non‐small‐cell lung cancer patients. A rare case of ALK‐positive squamous cell carcinoma of the lung is reported. A 60‐year‐old man, an ex‐smoker with a 720‐packs‐per‐year tobacco smoking history, presented with a mass lesion in the upper lobe of the left lung on chest computed tomography. Transbronchial biopsy of the mass confirmed a diagnosis of lung squamous cell carcinoma, and it was proven to have ALK rearrangement by fluorescent in situ hybridization. The patient underwent left upper lobectomy. Hematoxylin and eosin staining of the surgical specimen demonstrated the typical morphology of pure squamous cell carcinoma. The patient has been advised to attend regular check‐ups for postoperative recurrence. ALK testing and subsequent ALK‐targeted treatment can be a possible option in cases of postoperative recurrence.

Mediastinal mature teratoma with complete gastrointestinal and bronchial walls.

An extremely rare case of anterior mediastinal mature teratoma with almost complete gastrointestinal and bronchial walls is described. A 65‐year‐old woman presented with left precordial pain. Chest computed tomography showed a huge anterior mediastinal tumor, 15 cm × 21 cm, occupying the left thoracic cavity. Post‐resection histopathological examination confirmed the diagnosis of mature teratoma and demonstrated almost complete gastrointestinal and bronchial walls. Although mature teratomas of the ovary and sacrococcygeal area are known to rarely contain organoid structures with various degrees of differentiation, this is the first case of an anterior mediastinal mature teratoma that contained well‐developed organoid structures.

Intimal sarcoma of the abdominal aorta with platelet-derived growth factor receptor α overexpression and amplification in mural invasive cells and pulmonary metastatic cells but not in intimal spreading cells.

Intimal sarcoma (IS) is the most common sarcoma of the aorta. The platelet‐derived growth factor receptor α (PDGFRA), murine double minute 2 (MDM2), and cyclin‐dependent kinase 4 (CDK4) genes are often simultaneously amplified in IS. While immunohistochemical analysis of IS tissue has demonstrated frequent overexpression of the MDM2 and CDK4 proteins, the expression pattern of PDGFRA has not been well characterized, particularly in terms of intratumoral heterogeneity. Here, we present the case of a 46‐year‐old man who presented with a backache and was subsequently diagnosed with IS. Intratumoral heterogeneity of PDGFRA gene amplification was observed using fluorescence in situ hybridization and was positively correlated with PDGFRA protein expression using immunohistochemistry (IHC). The expression of PDGFRA was also correlated with cytological atypia: PDGFRA was not overexpressed in intimal spreading cells that displayed the lowest degree of atypia while PDGFRA overexpression and amplification were observed in invasive cells of progressive areas such as the aortic wall and a pulmonary metastatic site, which showed increased cytological atypia. Although PDGFRA has not been well examined on IHC, IHC of PDGFRA could be useful to diagnose IS. However, the areas within the tumor from which specimens are derived are important given potential intratumoral heterogeneity.

Tracheal segmental resection for tracheal cancer: comparison of cervical collar incision with median sternotomy and posterolateral incision

Abstract We compare two surgical approaches for segmental tracheal resection for tracheal cancer: cervical collar incision with median sternotomy and right posterolateral incision. In case one, a 46-year-old woman presented with adenoid cystic carcinoma, measuring 4.5 cm longitudinally, located at the junction of the cervical and mediastinal trachea. Cervical collar incision with median sternotomy provided a good exposure of the entire trachea. Although a relatively long tracheal resection (5.0 cm) was required, sufficient mobilization of the entire trachea facilitated low-tension anastomosis. In case 2, a 39-year-old man presented with squamous cell carcinoma, measuring 1.8 cm longitudinally, located at the lower trachea 1.8 cm from the carina to the proximal side. Right posterolateral incision provided a good exposure of the lower trachea. Although the required tracheal resection was relatively short (3.0 cm), the anastomotic tension was high. The high anastomotic tension was likely attributed to the limited mobilization of the proximal trachea.

Emergency surgery for lung cancer with abscess formation after transbronchial biopsy

Abscess formation in lung cancer after transbronchial biopsy (TBB) is a rare complication with no standard consensus on a coping strategy or prophylaxis. We describe an instructive case of lung cancer which developed into an abscess after TBB. An 80‐year‐old man with poorly controlled diabetes mellitus underwent TBB for diagnosing a mass lesion in the left upper lobe. The TBB specimen confirmed a diagnosis of lung cancer, and he was scheduled for radical surgery. However, the tumour was revealed to have progressed into an enlarged abscess 24 days after TBB. Prompt use of meropenem failed to relieve the infection, hence we performed emergency left upper lobectomy. Poorly controlled diabetes mellitus was considered to be a risk for the formation of a tumour abscess after TBB. It was difficult to control the infection with conservative treatment using antibiotics; emergency surgical resection was considered to be the safest strategy for recovery.

Descending necrotizing mediastinitis complicating hyperimmunoglobulin E syndrome.

Descending necrotizing mediastinitis (DNM) is a potentially lethal disease that originates from a deep neck infection (DNI); it is often associated with an immunocompromised state. Hyperimmunoglobulin E syndrome (HIES) is an extremely rare complex immune deficiency characterized by recurrent abscesses of staphylococcal etiology. A rare case of a 34‐year‐old woman wherein HIES putatively promoted the development of DNI into DNM is described. She presented with cervical purulent lymphadenitis and retropharyngeal abscess. Despite immediate cervical drainage and use of broad‐spectrum antibiotics, she developed DNI and subsequently DNM. Mediastinal drainage with thoracotomy and subsequent deep neck drainage were performed. Bacterial culture of the abscess isolated methicillin‐resistant Staphylococcus aureus (MRSA). Although a postoperative recurrent deep neck abscess required a second surgery, we succeeded in conservative remission of recurrent mediastinal abscess with long‐term use of anti‐MRSA drugs. Sufficient drainage under thoracotomy and robust administration of postoperative antibiotics resulted in successful management of HIES‐associated DNM.

Stromal micropapillary predominant lung adenocarcinoma: A rare histological phenotype with poor prognosis: Stromal micropapillary adenocarcinoma

An extremely rare case of stromal micropapillary predominant lung adenocarcinoma is presented in this study. A 70‐year‐old woman visited our hospital because of an abnormal shadow on chest X‐ray. Chest computed tomography revealed a nodule in the left lower lobe and a mass in the left upper lobe. She underwent an exploratory thoracotomy owing to the suspicion of advanced lung cancer. Pathological examination of the left lower lobe nodule revealed tumour cells with more than half the tumour cells showing stromal micropapillary pattern (SMP), consisting of tumour cells invading the fibrotic stroma. In general, micropapillary adenocarcinomas in the lung form an aerogenous micropapillary pattern (AMP), in which tumour cells float in alveolar spaces. Because the prognosis of SMP lung adenocarcinomas is known to be worse than that of AMP lung adenocarcinomas and have a high frequency of epidermal growth factor receptor mutations, the discrimination of SMP from AMP is important for both pathologists and clinicians.

Pulmonary micropapillary-type adenosquamous carcinoma sharing epidermal growth factor receptor mutation in adenocarcinoma and squamous cell carcinoma

Adenosquamous lung carcinoma (AdSqLC) has a worse prognosis than adenocarcinoma (ADC) or squamous cell carcinoma (SQCC). Micropapillary pattern in lung ADC is an additional poor prognostic factor. We describe a rare case of AdSqLC with epidermal growth factor receptor (EGFR) mutation in both the micropapillary‐ADC and SQCC components, showing long‐term response to gefitinib. A 60‐year‐old woman underwent right lower lobectomy for primary lung cancer. Histopathological examination demonstrated adenosquamous carcinoma comprising micropapillary‐ADC and moderately differentiated SQCC. EGFR exon 19 deletions mutation was detected in both the ADC and SQCC components. Gefitinib was administered for multiple metastatic recurrences on bilateral lung, resulting in remarkable shrinkage of visible lesions. The efficacy of gefitinib lasted for 31 months after the induction. AdSqLCs harbouring the EGFR mutation in both the ADC and SQCC components may well benefit from EGFR tyrosine kinase inhibitors, especially when they contain micropapillary‐ADC component that correlates with frequent EGFR mutations.