Mini Review

Intramural and Transmogrified - Adenocarcinoma in Situ Lung

Anubha Bajaj*

^*Histopathologist in AB Diagnostics, New Delhi, India

Submission: November 08, 2023; Published: December 05, 2023

*Corresponding Address: Anubha Bajaj, Histopathologist in A B Diagnostics, New Delhi, India

How to cite this article: Anubha Bajaj*. Intramural and Transmogrified - Adenocarcinoma in Situ Lung. Canc Therapy & Oncol Int J. 2023; 25(4): 556168. DOI:10.19080/CTOIJ.2023.25.556168

Mini Review

Adenocarcinoma in situ and minimally invasive adenocarcinoma manifest up to 14% of primary pulmonary malignancies. Alternative terminology of bronchioloalveolar carcinoma is considered obsolete. Adenocarcinoma in situ lung is an uncommon variant of bronchial carcinoma. Adenocarcinoma in situ manifests as a pre-invasive pulmonary adenocarcinoma of magnitude ≤ 30.0 millimetres. The subcategory of pulmonary adenocarcinoma represents significantly diverse clinical manifestations, applicable therapeutic options and prognostic outcomes. Tumefaction exhibits a pure ‘lepidic’ pattern of tumour evolution wherein tumour infiltration is absent. Appropriate discernment of adenocarcinoma in situ necessitates thorough sampling of the entire neoplasm. Adequate tumour detection upon evaluation of miniature tissue samples or cytological smears may be challenging.

Characteristically, neoplasm exhibits a lepidic pattern of tumour evolution along with an absence of tumour invasion within subjacent stroma, vascular spaces or pleura. Classically, tumour magnitude is ≤ 30.0 millimetres [1,2]. An estimated 50% lesions of adenocarcinoma in situ delineate EGFR genetic mutations.

Additionally, KRAS genomic mutations are encountered. Incidence of aforesaid EGFR mutation appears enhanced in incriminated Asians whereas KRAS mutations are frequently observed in Caucasians. Besides, molecular assessment is recommended while treating subjects with cogent targeted therapy. Genetic mutations within TP53 and NF1 contribute to frequent emergence of adenocarcinoma in situ and minimally invasive adenocarcinoma lung. Adenocarcinoma in situ and minimally invasive adenocarcinoma lung are associated with significant copy number loss, in contrast to occurrence of deleterious chromosomal mutations [1,2]. Adenocarcinoma in situ exhibits diverse subtypes as.

i. Non-mucinous subtype is frequent.

ii. Mucinous subtype is exceptional.

iii. Mixed subtype is infrequent.

iv. Lepidic histological configuration is characteristically accompanied by an absence of tumour necrosis or invasion. Adenocarcinoma in situ configures ~5% of non-small cell lung carcinomas (NSCLC). A mild female predominance or an equivalent gender predilection is observed. Adenocarcinoma in situ lung frequently emerges within nonsmokers, female subjects and Asian population. Besides, adenocarcinoma in situ may arise within preceding focus of pulmonary fibrosis as enunciated with scarring of tuberculosis, pulmonary infarct or scleroderma.

i. Adenocarcinoma in situ is commonly confined to peripheral pulmonary lobes [1,2]. Emergence of adenocarcinoma in situ is concordant with multistep tumour progression denominated as Adenocarcinoma in situ (AIS) configures as an intermediate lesion between atypical adenomatous hyperplasia (AAH) and minimally invasive carcinoma (MIA).

ii. Incidence of EGFR chromosomal mutations within atypical adenomatous hyperplasia towards adenocarcinoma in situ and minimally invasive carcinoma demonstrates an increasing order of frequency. iii. KRAS and BRAF genetic mutations may not display concordant progression, thereby indicating activation of alternative molecular alterations within neoplastic emergence. ~EPPK1, KMT2C, KMT2D, NOTCH3 and NF1 chromosomal mutations may manifest as preliminary elements within progression of pulmonary adenocarcinoma [1,2].

Akin to invasive pulmonary adenocarcinoma, cigarette smoking or tobacco consumption is posited to induce adenocarcinoma in situ. Nonsmokers may depict neoplastic appearance due to exposure to passive smoke or radon. Besides, occupational exposure or air pollution may configure the lesion [1,2]. Most pulmonary carcinomas encountered within nonsmokers emerge as idiopathic neoplasms and depict varied chromosomal mutations, in contrast to cigarette smoking induced pulmonary carcinoma. Adenocarcinoma in situ is an incidentally discovered, gradually progressive lesion and may configure a singular tumefaction. Alternatively, lesion may concur with distinct focus of invasive adenocarcinoma [3,4]. Cytological examination exhibits mild to moderate cellular and nuclear atypia. Nuclear membrane appears irregular. Nuclear grooves and intra-nuclear pseudo-inclusions, reminiscent of papillary thyroid carcinoma may be observed. Categorical neoplastic discernment mandates histological evaluation of surgical tissue samples [3,4].

Upon frozen section, adenocarcinoma in situ exhibits lepidic pattern of tumour evolution. Mild to moderate cytological atypia is observed. Not with standing, appropriate categorization as adenocarcinoma in situ upon frozen section may be challenging. Besides, tumour invasion may emerge within deep seated neoplastic foci or tumour unassessed by frozen section examination [3,4]. Neoplasm diagnosed by singular frozen section devoid of tumour invasion may be labelled as adenocarcinoma in situ with lepidic pattern wherein additional evaluation with permanent, formalin fixed paraffin embedded sections obtained from residual tumour appears imperative. Grossly, adenocarcinoma in situ emerges as a poorly defined nodule. Collapsed or compressed tumour nodules may appear solid. Tumefaction may be associated with a scar. Tumour magnitude is ≤ 30.0 millimetres [3,4]. Upon microscopy, lesions are demonstrated.

i. Lepidic growth pattern configured of intensely adherent, back-to-back neoplastic cells singularly expanding along pre-existing alveolar structures. Tumour magnitude is ≤ 30.0 millimetres. Foci of stromal, vascular or pleural tumour invasion or tumour necrosis appear absent. Neoplasm may be detected singularly upon thorough sampling of surgical resection specimens. Neoplastic determination upon evaluation of miniature tissue samples, cytological smears or frozen section appears challenging. Distinction is necessitated from minimally invasive adenocarcinoma or invasive adenocarcinoma lung.

ii. Non-mucinous adenocarcinoma in situ exhibits mild to moderate cytological atypia and represents with an amalgamation of morphological features as hobnail cells, anisocytosis, irregular nuclear membrane, intra-nuclear pseudo-inclusions, nuclear grooves, hyperchromatic nuclei, miniature nucleoli or elevated nucleocytoplasmic ratio.

iii. Mucinous adenocarcinoma in situ is an extremely exceptional mucinous neoplasm demonstrating infiltration of adjacent pulmonary parenchyma. Mucinous tumour cells are permeated with abundant intracellular mucin and basal nuclei. Neoplastic cells exhibit minimal cellular and nuclear atypia. iv. Adenocarcinoma in situ is constituted of lesion ≤3.0-centimetre magnitude. Neoplasm demonstrates lepidic pattern of tumour evolution and disseminates along alveolar walls wherein pulmonary architecture remains unaltered. Characteristically, absence of stromal, vascular or pleural invasion is enunciated [4,5] (Figures 1 & 2) (Table 1).

Adenocarcinoma in situ lung demonstrates immune reactivity characteristically simulating the immune reactive pattern of adenocarcinoma lung. Tumour cells appear immune reactive to CK7, thyroid transcription factor-1 (TTF-1) or Napsin A. Neoplastic cells appear immune non-reactive to CK20 or p40 [5,6]. Adenocarcinoma in situ lung requires segregation from pulmonary neoplasms such as atypical adenomatous hyperplasia, minimally invasive adenocarcinoma, adenocarcinoma, lepidic predominant, bronchiolar adenoma, glandular papilloma, papillary adenoma or peribranchial metaplasia. Besides, demarcation from lesions manifesting with solitary pulmonary nodule, chronic alveolar opacity or ground glass opacity is required [5,6]. Adenocarcinoma in situ lung may or may not be discernible upon computerized tomography (CT) or magnetic resonance imaging (MRI). Appropriate detection is contingent to tumour magnitude and accompanying scar tissue. Indolent lesions delineate.

i. Miniature magnitude.

ii. Extended volumetric doubling time exceeding > 400 days.

iii. Maximum standardized uptake value (SUV) < 1 [5,6].

Nevertheless, definitive lesion discernment necessitates surgical extermination followed by cogent histopathological evaluation. Plain radiographs depict a non-solid, partially solid or solid tumefaction. Additionally, neoplasm may be mucinous or demonstrates a scar. Adenocarcinoma in situ lung can be optimally treated with comprehensive surgical eradication, a maneuver which is diagnostic and may appropriately alleviate the lesion [5,6]. Adjuvant chemotherapy or radiotherapy remains superfluous. Comprehensive surgical extermination of lesion is associated with 100% disease free and reoccurrence free proportionate survival. Tumours unamenable to surgical eradication may progressively enlarge, contingent to factors such as initial tumour magnitude, history of cigarette smoking and status of chromosomal mutations [5,6].

References

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5. Yotsukura M, Asamura H, Motoi N, Jumpei K, Yukihiro Y, et al. (2021) Long-Term Prognosis of Patients with Resected Adenocarcinoma in Situ and Minimally Invasive Adenocarcinoma of the Lung. J Thorac Oncol 16(8): 1312-1320.
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