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• Rewriting "Little Red Riding Hood" story may be dangerous
  Giulio Rossi
  Published on: 18 April 2016

• Published on: 18 April 2016

  Rewriting "Little Red Riding Hood" story may be dangerous

  • Giulio Rossi, Surgical Pathologist
  • Other Contributors:
    • Maria Cecilia Mengoli, Giuseppe Bogina, Alberto Cavazza

  Rewriting "Little Red Riding Hood" story may be dangerous

  Maria Cecilia Mengoli,1 Giuseppe Bogina,2 Alberto Cavazza, 3 Giulio Rossi 1

  1Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy 2Section of Pathologic Anatomy, Hospital "Don Calabria", Negrar, Verona, Italy 3Department of Oncology and Advanced Technologies, Operative Unit of Oncology, Arcispedale S. Maria Nuova /...

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  Rewriting "Little Red Riding Hood" story may be dangerous

  Maria Cecilia Mengoli,1 Giuseppe Bogina,2 Alberto Cavazza, 3 Giulio Rossi 1

  1Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy 2Section of Pathologic Anatomy, Hospital "Don Calabria", Negrar, Verona, Italy 3Department of Oncology and Advanced Technologies, Operative Unit of Oncology, Arcispedale S. Maria Nuova / I.R.C.C.S., Reggio Emilia, Italy

  Corresponding author: Giulio Rossi, MD Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico Via del Pozzo, 71 - 41124 Modena (Italy) Telephone: +39.059.4223890; Fax: +39.059.4224998; Email: giurossi68@gmail.com

  To the Editor:

  We greatly appreciated the work by Klebe et al1 on the different results of TTF-1 expression in lung and pleural neoplasms using different clones, namely 8G7G3/1 and SP141. The authors reported TTF1 expression with clone SP141 in normal bronchial mucosa, in about half of squamous cell carcinomas and in 42% of sarcomatoid pleural mesotheliomas. By contrast, no expression was noted with 8G7G3/1 in the same tissues. We recently shared the same experience when clone SP141 momentarily substituted 8G7G3/1 in our Lab. In addition, several colleagues sent us in consultation cases of morphologically-overt squamous cell carcinomas expressing p63 or p40 as well as strong TTF-1 positivity, TTF-1 positive mesotheliomas and metastatic carcinomas from breast and gastrointestinal tract cancers. The last TTF-1 positive case with clone SP141was a minute mucous gland adenoma (Fig. 1A-B) incidentally discovered at bronchoscopy in a 75 year-old man with a previous history of papillary carcinoma of the thyroid. The positive staining with SP141 (Fig. 1C) raised the possibility of a metastasis from thyroid cancer, but clinical and imaging findings, and morphology strongly favoured a benign lesion from bronchus-associated salivary glands. Indeed, TTF-1 staining with clone 8G7G3/1 was restricted to entrapped pneumocytes (Fig. 1D).

  Figure 1. Bronchoscopy showing an endobronchial millimetric lesion with smooth, glistening surface (A) histologically appearing as well- defined, submucosal proliferation of mucous-filled enlarged bland-looking glands consistent with a mucous gland adenoma (B). Bronchial mucosa and mucous glands expressing TTF-1 clone SP141 (C), while TTF-1 clone 8G7G3/1 stained only few entrapped pneumocytes (D).

  When pathologists begun to use TTF-1 immunostaining in pulmonary tissue in discriminating primary lung tumours from metastatic malignancies or to distinguish some benign or malignant entities among a large spectrum of pulmonary lesions, 8G7G3/1 was the only commercially available clone. Then, we learned a huge amount of information from several studies robustly indicating the diagnostic value of TTF-1 positivity and negativity in different thoracic conditions (Table 1).

  Table 1. A brief summary of positive and negative thoracic tumours with TTF-1 clone 8G7G3/1

  Positive tumors Papillary adenoma Sclerosing hemangioma/pneumocytoma Pneumocytic adenomyoepithelioma Carcinoid tumors ? Large cell neuroendocrine carcinoma (about 60%) Small cell lung cancer (about 80%) Atypical adenomatous hyperplasia Adenocarcinoma * Negative tumors Alveolar adenoma Salivary gland tumors Squamous cell carcinoma Mesothelioma

  ?, positivity is mainly restricted to peripheral-type carcinoids; *, some variants of adenocarcinoma (e.g., mucinous, colloid, enteric types) may be entirely negative

  TTF-1 powerfully entered in all labs of surgical pathology and promptly appeared as one of the most reliable antibody in the routine practice. By the way, controversial issues with TTF-1 clone 8G7G3/1 expression occurred in neuroendocrine tumours (staining in peripheral rather than central carcinoids or positivity in high-grade extrapulmonary neuroendocrine carcinomas)2,3 or in a subset of metastatic tumors to the lungs (e.g., gynaecological tumours).4 Although it is unclear the significance of the higher sensitivity/affinity for TTF-1 protein of clone SP141 (or SPT24) when compared with clone 8G7G3/1, in our hands a weak nuclear signal from clone G8G7G3/1 does appear more sincere than a strong signal from clone SP141. TTF1 clone 8G7G3/1 is far from being perfect, but the higher specificity of this clone in subtyping non-small cell lung cancer (NSCLC) and in discriminating lung adenocarcinoma from mesothelioma or metastatic cancers is not renounceable.5,6 Keeping in mind that the majority of thoracic tumours may be likely diagnosed on morphology alone and immunohistochemistry is an ancilla of the haematoxylin-eosin stain, the lessons learned from the story of TTF-1 immunostaining clearly indicate that the clone SP141 does represent the "wolf in grandma", while clone 8G7G3/1 is the "good grandmother".

  References

  1. Klebe S, Swalling A, Jonavicius L, Henderson DW. An Immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma. J Clin Pathol 2015 doi 2. Du EZ, Goldstraw P, Zacharias J, et al. TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1 positive carcinoids are predominantly in peripheral location. Hum Pathol 2004;35:825-831. 3. Agoff SN, Lamps LW, Philip AT, et al. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol 2000;13:238-242. 4. Siami K, McCluggage WG, Ordonez NG, et al. Thyroid transcription factor -1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2007;31:1759-1763. 5. Ordonez NG. Value of thyroid transcription factor-1 immunostaining in tumor diagnosis: a review and update. Appl Immunohistochem Mol Morphol 2012;20:429-40. 6. Kadota K, Nitadori J, Rekhtman N, Jones DR, Adusumilli PS, Travis WD. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using Immunohistochemical analysis. Am J Surg Pathol 2015;39:1170-80.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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