Primary pulmonary invasive mucinous adenocarcinoma with sigmoid colon metastasis:a case report and literature review

Background: Invasive mucinous carcinoma is a very rare tumor. The colonic metast-asis of IMA is more infrequent. So far, no literatures are published. Case presentation: We report a case of a patient with invasive mucinous adenocarci-noma. After serial months of chemitherapy, the sigmoid colonic metastasis was detected. Conclusions: Symptoms and CT ndings can initially be subtle, histological examination remains the gold standard for the denitive diagnosis. Patients with high grade primary lung cancer may have gastrointestinal metastases, therefore their gastrointestinal should be examined to allow early detection and treatment.

was positive, gram-positive and gram-negative bacteria were found. Tuberculosis (TB) was ruled out. The remainder of the infectious work-up including AFB smear, mycobacterial cultures, BAL uid bacterial cultures and HIV antigen/antibody combo were negative. An autoimmune panel, including ANA, ANCA and myositis autoantibodies was negative, except ANA and anti Ro-52 (+). The patient was therefore started on cefoperazone-sulbactam and levo oxacin in addition to broad spectrum antibiotic therapy. After ten-days treatment, the patient's respiratory symptoms showed mild improvement, but the multifocal pulmonary in ltrations remained unchanged. Therefore CT-guided percutaneous lung biopsy in right lower lobe was performed. Histopathologically, the tumor consisted of abundant mucin lling the alveolar spaces and some tumor cells oating in mucin pools. Columnar mucinous epithelial cells lined thickened alveolar walls (Fig. 2), Immunohistochemistry (IHC) showed neoplastic cells positive for CK7, negative for TTF-1, CK20, CDX2, ALK(lung) and P63. We nally diagnosed invasive mucinous adenocarcinoma of the lung (moderate to poorly differentiated stage T4N2M0, stage IIIB). Further tumor mutation analysis was examined, EGFR mutation was negative and KRAS mutation at the 17 exon (p.G12 D mutation) was detected. Chemotherapy was started for pulmonary mucinous adenocarcinoma. After four cycles of treatment, in August, 2020, CT examination from chest to pelvis was performed which revealed localized thickening of sigmoid wall (Fig. 3). The patient was sent to an endoscopy room, and colonoscopy suggested the possibility of colon cancer, so biopsy was performed. IHC showed CK7(-), TTF-1(+), CK20(+), CDX2 (+) ,Ki-67(Li:80%) (Fig. 4), CerB-2(-). Finally, metastatic lung mucinous adenocarci-noma (enteric adenocarcinoma) was diagnosed. About a month later, the patient had severe abdominal pain and passed away nally. We speculated that she was died of enterobrosis and septic shock.

Discussion
Primary pulmonary invasive mucinous adenocarcinoma (IMA) is an adenocarcinoma variant according to the current World Health Organization (WHO) classi cation of lung tumors [11], formerly known as mucinous bronchioloalveolar carcinoma (BAC), which is relatively rare [3].
IMA has a range of differences from those of invasive non-municous adenocarcinoma (INMA), including genetic, clinical, radiological and pathological characteristics. The age of IMA patients ranged between 41 and 66 years and the majority were non-smoking females [12]. Clinical features are generally nonspeci c, such as cough, fever, expectoration and dyspnea etc. The symptom of coughing with white sputum may help early diagnosis of pneumonic-type adenocarcinoma [13]. In the present study, it was revealed that the patient was female and non-smoker, as well as mild coughing with white sputum when she was initially diagnosed, which were consistent with previous study [13].
IMC displays a variety of radiological presentations. According to the CT ndings, IMC has been classi ed into three patterns [14]: solitary nodules or masses; localized consolidation, pneumonic types; multicentric or diffuse disease, most patients have a mixture of these features. The most common features on chest high-resolution computed tomography (HRCT) scan are predominant ground-glass opacities, consolidations, or multiple nodules [15]. Because of the nonspeci c radiographic ndings, we may usually not differentiate them from other lung diseases, such as atypical pneumonia, tuberculosis, pulmonary lymphoma or metastatic lung cancer [15,16]. However some studies [17][18][19] reported that the pneumonic types IMA had air bronchograms with stretched, sweeping, narrowed appearance and bulging of the interlobar ssure. In our report, the patient was initially misdiagnosed as focal organizing pneumonia, but after ten days of anti-in ammatory therapy, the lesions are not eliminated, ultimately we got an accurate diagnosis by percutaneous computer tomography (CT)-guided lung biopsy. we reviewed her chest CT imagings carefully, some signs were found, such as air bronchograms with a stretched, sweeping and bulging of the interlobar ssure, which can help the differential diagnosis. Percutan-eous computer tomography (CT)-guided lung biopsy appears to be an effective way to make a de nitive diagnosis.
Immunohistochemistry is very valuable for determining the primary origins. Among those, CK7, CK20, CDX2, and TTF-1 has been proven to be diagnostic [6]. Most pulmonary adenocarcinomas are typically positive for TTF-1 and CK 7, and negative for CK 20 [71][72][73][74]. Most colorectal adenocarcinomas are negative for TTF-1 and CK 7, and positive for CK 20 [75][76]. However, up to 20% of lung adenocarcinomas are reported to be negative for TTF-1, and up to 30% may react positively with CK 20. Several studies showed CDX-2 to be highly sensitive for colorectal ACA, but among lung tumors, only a rare type of pulmonary ACA, the goblet cell variant of primary mucinous (so-called colloid) ACA, has been reported to be positive for CDX-2 [77]. TTF-1 is expressed only in lung cancer and thyroid cancer [77][78][79][80][81]. The expression of TTF-1 rate in IMA is often lower than that in non-mucinous adenocarc-inoma. In addition, according to the report of Su et al [12], the positive rates of primary lung adenocarcinoma were 73% for TTF-1, 75% for CK7, and 0% for CK20, the positive rates of primary colon cancer were reported to be 0% for TTF-1, 7% for CK7, and 86% for CK20. Thus, since TTF-1 expression is lacking in all adenocarci-noma types except for lung adenocarcinoma, which is very important to distinguish between primary adenocarcinoma and metastatic adenocarcinoma.
KRAS mutations are the most requent oncogenic driver mutations in IMAs (up to 86%) [82,83]. the most common types are G12D and G12V in IMAs [83]. KRAS mutation has been reported to be associated with invasive mucinous adenocarcinoma, formerly known as mucinous BAC [84]. For our patient, the lung lesion was immun-oreactive for CK7, favoring the diagnosis of lung adenocarcinoma. Negative staining of p63 rules out squamous cell carcinoma of the lung. KRAS mutation (p.G12 D mutation) was positive.
The sigmoid lesion was immunoreactive for TTF-1, CK 20, CDX2. The positive expression of TTF-1 indicated that her sigmoid tumor was metastatic from pulmonary carcinoma. Because of the primary pulmonary mucinous adenocarcinoma, CDX2 can be positive. These IHC stains can help determine the primary tumor and distinguish metastatic carcinoma from primary tumor.

Conclusion
Our report represents an exceedingly rare case of primary pulmonary invasive mucinous adenocarcinoma metastatic to sigmoid colon. Symptoms and CT ndings can initially be subtle, histological examination remains the gold standard for the de nitive diagnosis. Patients with high grade primary lung cancer may have gastrointestinal metastases, therefore their gastrointestinal should be examined to allow early detection and treatment. Microscopic examination at a magni cation of ×200 shows mucinous tumor cells consisting of tall columnar cells with abundant apical mucin.