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Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation

Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 4150924, 7 pages https://doi.org/10.1155/2020/4150924 Case Report Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation 1 2 Swati Pandey and Shishir Ojha Elkhart General Hospital, 600 East Blvd, Elkhart, IN 46514, USA Elkhart General Hospital, Beacon Medical Group Pulmonology, 500 Arcade Avenue, Suite 210, Elkhart, IN 46514, USA Correspondence should be addressed to Shishir Ojha; ojha_sh@yahoo.com Received 15 May 2019; Accepted 26 October 2019; Published 24 November 2020 Academic Editor: Jose I. Mayordomo Copyright © 2020 Swati Pandey and Shishir Ojha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The diagnosis of lymphangitic carcinomatosis is challenging due to the manifestation of nonspecific symptoms and radiographic abnormalities that bear similarity to those of interstitial lung disease. Herein, we report the case of a 53-year-old woman diagnosed with lymphangitic carcinomatosis from metastatic gastric adenocarcinoma, 3 months after her initial presentation. 1. Case Laboratory findings were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies. A 53-year-old female was referred to the pulmonary clinic Video-assisted thoracic surgical biopsy and transbronchial due to cough and chest pressure for the past 3 months, dur- cryobiopsy were discussed, and the risks and benefits of each ing which several chest X-rays and a computed tomography procedure were explained. She chose to undergo a transbron- (CT) scan of the chest were taken. She was initially expecto- chial cryobiopsy, which was performed 3 months after her rating green sputum; however, the sputum production initial presentation to PCP. Three cryobiopsy samples were reduced after she received antibiotics from her primary care obtained—two from the lateral basal segment and one from physician (PCP). Additionally, she received two courses of the posterior basal segment of the right lower lobe—for path- steroids from visits to the emergency department, which sta- ologic evaluation. Additionally, four forceps biopsy samples bilized her cough. The patient also had occasional symptoms were collected—two each from anterior basal and superior of postprandial bloating. segment of the right lower lobe—for microbiological evalua- She was a lifelong nonsmoker, who worked in farms and tion. The pathology samples were sent to a tertiary care denied any exposure to molds or pets. During examination, center to be reviewed by a pulmonary pathologist with exper- she was afebrile with an oxygen saturation of 87% on room tise in ILD. air inhalation. Her physical exam revealed coarse breath Based on the morphology, the patient was diagnosed with sounds on auscultation and decreased breath sounds at the a tumor that was characterized as metastatic adenocarci- level of the left lung base posteriorly. A CT scan of her chest noma with lymphangitic spread (Figures 2 and 3). Tumor (Figure 1) showed bilateral linear coarse reticulations with no cells were positive for keratin and negative for CD31, thus peripheral predilection or ground-glass opacities and a small confirming the diagnosis. A second round of histological amount of left pleural effusion; the abdomen did not show staining was negative for thyroid transcription factor-1, any abnormality in the CT scan. Based on her symptoms GATA 3, mammaglobin, and gross cystic disease fluid and chest CT findings, we suspected a diagnosis of interstitial protein-15 (GCDFP-15), thereby excluding the lungs and lung disease (ILD). breast as primaries. As CDX2 was strongly positive, gastric 2 Case Reports in Oncological Medicine Figure 1: Chest CT scan. Figure 2: Hematoxylin and eosin-stained slide of cryobiopsy of lung. Arrow pointing to lymph-vascular invasion of tumor cells. primary was suspected. The differential diagnosis in the Thereafter, the patient underwent a repeat CT scan of the upper gastrointestinal primary or pancreatobiliary primary abdomen and pelvis, which did not reveal any mass or abnor- at this stage of staining supported the assumption. mality to suggest a primary. Three weeks after the Case Reports in Oncological Medicine 3 Figure 3: Hematoxylin and eosin-stained slide of cryobiopsy of lung. Arrow pointing to adenocarcinoma. bronchoscopic biopsy, she underwent an upper endoscopy, of this rare pattern, accounting for only 26.4% of pulmonary which revealed an ulcerated gastric mass occupying the car- metastasis [1]. Gastric lesions or abnormality in other viscera dia and antrum of the stomach. Biopsies from the mass were absent on the CT scan of the abdomen. Her chest CT revealed moderate to poorly differentiated invasive adeno- revealed interlobular septal thickening. The absence of medi- astinal or hilar lymph node enlargement and lung masses or carcinoma with lymphovascular invasion (Figure 4). Two days after the endoscopic biopsies, the patient was nodules excluded a diagnosis of malignancy. Despite wide- seen by an oncologist in an outpatient setting where several spread pulmonary parenchymal abnormalities, there was chemotherapy options ranging from aggressive regimens, no lymph node involvement. Mediastinal or hilar lymph- such as FOLFOX, to the least aggressive 5 FU with leucovorin adenopathy is commonly seen with lymphangitic spread were discussed. However, the patient declined the treatment. [2], but lymph node involvement is not essential. The Subsequently, she was hospitalized three times, 2 weeks mechanism of lymphangitic spread is hematogenous apart, for worsening dyspnea and was treated with thoracent- tumor embolism to the lungs and rarely due to contiguous esis on each occasion. During her last admissions, a chest lymphangitic spread [3]. tube was placed due to iatrogenic pneumothorax after thora- The diagnosis of metastatic cancer with pulmonary carci- centesis. The patient experienced worsening dyspnea and nomatosis is often delayed by months from the onset of hypoxemia, and comfort measures were initiated. The symptoms and imaging studies. This delay is mainly due to patient died 10 days after the last hospitalization, about 2 two attributes that are strongly associated with its presenta- months after her diagnosis. tion and imaging studies. First, patient characteristics play an important role. Most patients present with dry cough and dyspnea due to pulmonary parenchymal involvement, 2. Discussion irrespective of the origin of the primary. Hence, the workup We report the case of occult gastric malignancy with pulmo- for the symptoms is performed and does not involve imaging nary lymphangitic carcinomatosis (PLC). or diagnostic tests, which can reveal the primary. A patient’s Pulmonary metastasis is rare with gastric cancer, repre- age is usually less than that of a typical lung cancer patient because a wide variety of cancers that occur at a young age senting less than one percent of distant metastasis. The most commonly seen pattern of pulmonary metastasis is hematog- may present with lymphangitic spread. Patients are often enous which accounts for 52.3%, followed by pleural metas- nonsmokers, thereby lowering the suspicion for lung cancer. tasis (35.2%), and lymphangitic spread is the least common Moreover, patients are often empirically treated with 4 Case Reports in Oncological Medicine Figure 4: Hematoxylin and eosin-stained slide of Gastric Biopsy: arrow pointing to gastric adenocarcinoma. The reason for the delay in the diagnosis of PLC can be antibiotics for presumed respiratory tract infection and inhalers for dyspnea. due to the misinterpretation of the presentation and radio- Second, a radiologist is often misled by imaging patterns, graphic abnormality by the treating physician, and such whether on chest X-ray or chest CT, and the requesting phy- delay reduces patients’ duration of survival after diagnosis. sician may be convinced of an ILD diagnosis. The CT pattern Compounding this grave situation is that patients spend their of PLC is very similar to that of many ILDs, including sar- remaining life under intensive care while undergoing inva- coidosis, which is an arduous task to differentiate. Subtle dif- sive procedures to diagnose what was misinterpreted as ferences do exist, but these are not easy to spot and include a ILD. The overall 5-year survival rate for lung cancer for all great involvement of the interlobular septa and interstitium stages is 19.4% [21]. In comparison, as depicted in the table, in PLC and more distortion of secondary pulmonary lobule several diagnoses of PLC occurred in the intensive care unit due to fibrosis in sarcoid [4]. Thus, owing to the clinical pre- on vented patients, and most of them died within a day to sentation and radiographic patterns, our focus was on the few weeks thereafter. diagnosis of an underlying primary pulmonary parenchymal The misinterpretation of PLC as an ILD is more likely to occur if the imaging study shows findings of only pulmonary disease, specifically an ILD, rather than casting a wider net, which would have included an examination for malignancy. carcinomatosis, i.e., only interstitial changes, which are very We performed a literature search using the PubMed data- similar to many ILDs, without lung mass or a nodule. base for studies reporting cases of lymphangitic carcinomato- Although many ILDs present with lymph node enlargement, sis that were suspected as an ILD by treating physicians. The the presence of mediastinal or hilar lymph node enlargement raises the suspicion of malignancy. extracted publications are listed in Table 1 [5–18]. Informa- tion on the types of delays that occurred in the case reports The patient in this case report did not have mediastinal or are listed (Table 1), which included time interval from the hilar lymphadenopathy, unlike most patients with pulmo- first occurrence of a symptom to the first contact with a phy- nary carcinomatosis who have lymphadenopathy. If medias- sician and the interval from symptoms onset, diagnosis, and tinal or hilar lymphadenopathy were present, then a much more conservative approach, such as biopsy of the lymph presentation to death. Delays in the diagnosis of primary lung cancer diagnosis node with endobronchial ultrasound with or without trans- range from 7 days to 6 months and from onset of symptoms bronchial forceps biopsy, would have been considered. to contact with a physician [19]. The largest trial that has Instead, due to the presentation, a much more invasive investigated 380 consecutive patients with primary lung can- approach than needed for the diagnosis of malignancy, such as transbronchial cryobiopsy, was undertaken. Transbron- cer found that the median duration from the onset of symp- toms to visit with a physician was 7 days, that from the chial cryobiopsy is a new technique that enables pulmonolo- physician’s visit to diagnosis was 31 days, and that from gists to obtain a larger specimen than the traditional symptom onset to diagnosis was 50 days [20]. As depicted, transbronchial forceps biopsy [22], but whether it can serve the wait times are similar to the delays in the diagnosis of pri- as an alternative to surgical biopsy for the diagnosis of ILDs is a subject of investigation. Nevertheless, the risks of mary lung cancer. Case Reports in Oncological Medicine 5 Table 1: Case reports of PLC suspected as an ILD. S. NO 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 7 31 45 53 63 62 62 39 24 30 30 25 62 Age/gender F M F F F M F M F M M M M M Cough, Progressive Dry cough, night Dry cough, night Dyspnea, dry sob, lethargy, Respiratory Productive cough Progressive dyspnea, Worsening Dyspnea, dry Cough, sob, fever, Cough, dyspnea Symptoms Dry cough, dyspnea Dry cough dyspnea and sweats, dyspnea sweats, dyspnea on cough fever for satiety, distress and dyspnea weight loss, and rash. dyspnea cough. and chest pain. on exertion cough hemoptysis exertion, weight loss six weeks anorexia Mediastinal Enlarged med Subpleural Interstitial and Interstitial Diffuse Ground glass opacities, Thickening of Mediastinal Mediastinal lymphadenopathy. Interlobular septal LN, diffuse reticulations ground-glass thickening, crazy reticulonodular and diffusely thickened peribronchovascular, lymphadenopathy Diffuse Bilateral opacities. Thickened lymphadenopathy, Thickened thickening, scattered reticular pulmonary Chest CT paving, ground-glass interlobular septa, interstitial, and and interstitial interstitial interlobular septa B/l interstitial interlobular septa, GGO, nodularity along thickening, nodules, Borderline mediastinal opacities, pleural mediastinal and hilar interlobular septa. reticulonodular prominence infiltrates infiltrates ground-glass fissures, reticular-nodular enlarged mediastinal lymphadenopathy effusions LN enlarged Ground glass opacities interstitial pattern. opacities pattern. mediastinal LN lymphadenopathy Bronchoscopy Bronchoalveolar Bronchoalveolar Bronchoalveolar Bronchoalveolar could not be lavage. Central lavage showed atypical Transbronchial Transbronchial Bronchoalveolar Transbronchial lavage negative, lavage and VATS surgical completed. Open lung Diagnostics Open lung biopsy Open lung biopsy Open lung biopsy bronchoscopic cells. Transbronchial biopsy, prostate biopsy lavage biopsy cervical skin biopsy transbronchial biopsy Diagnosed by biopsy biopsies. Gastric origin biopsies could not be biopsy positive biopsy surgical lung by EGD. done. biopsy Signet ring Gastric Signet ring cell gastric Adenocarcinoma Renal Adenocarcinoma of Signet ring gastric Signet ring gastric Pulmonary Gastric Pulmonary Pulmonary Prostate Diagnosis Melanoma gastric adenocarcinoma with adenocarcinoma on unknown primary adenocarcinoma colon adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma signet ring. EGD biopsy adenocarcinoma focal Symptom onset to 107 NA 180 117 Over 30 days 150 180 NA NA 60 60 NA 379 42 diagnosis (days) Symptom to 108 NA 191 119 NA 159 180 NA NA NA NA NA 382 NA death (days) Presentation to death 70 NA 16 29 NA NA 67 NA NA NA NA NA 17 NA (days) Diagnosis to 1NA 11 12 NA 7 7 NA NA NA NA NA 3 NA death (days) Prednisone, Ciprofloxacin and clarithromycin, erythromycin for Piperacillin- Therapy Steroids for Vancomycin and Broad-spectrum salbutamol, bronchitis, right heart Antibiotics and Immunosuppressive tazobactam, Not applicable. prior to NA sarcoidosis. Folfox piperacillin- NA Steroids antibiotics for 14 days, NA Antibiotics. antitubercular, Cath, sildenafil, and steroids therapy ciprofloxacin, and Survived. diagnosis after diagnosis tazobactam high dose steroids antipneumocystis ambrisentan for Pulm oseltamivir therapy. HTN. ICU. Biopsy while Setting of Post biopsy, ICU, ICU on vent ICU vent NA intubated, palliative Non-ICU setting NA Not in ICU NA NA Na NA ICU NA diagnosis vent support postdiagnosis Contralateral Abdominal wall, tibia, Thoracic and pulmonary and Lung, pleura, right ribs, Metastasis Not available (NA) NA femur, right humerus, NA NA Skin NA NA NA NA NA lumbar spine spinal right iliac bone lumbar spine metastasis. Guler et al. [12], Gleason et al., J of Vanclaire et al., Biswas et al., Am Dikis et al., Journal of Mapel et al., Cohen et al. Gilchrist et al., Eur Thomas and Lenox, Khachekian et al., J Am Wang et al., Poster, clinical and Moubax et al., BMC Meltem et al., Turkish Blanco et al., An Author Arch Fr Pediatrics Journal of Clinics in Surgery clinical Lung Cancer [18], Resp Review [5] CMAJ [7] Osteopath Assoc. [8] chest meeting [11] diagnostic research research notes [14] thoracic journal [15] Med Interna [16] Medicine [9] [10] respiratory [6] [17] Respiration [13] disease & care. 6 Case Reports in Oncological Medicine [7] A. Thomas and R. Lenox, “Pulmonary lymphangitic carcino- pneumothorax and bleeding are higher than those of forceps matosis as a primary manifestation of colon cancer in a young biopsy [23], but the overall morbidity is lower than that of adult,” Canadian Medical Association Journal, vol. 179, no. 4, surgical lung biopsy [23]. Therefore, patients with PLC pp. 338–340, 2008. undergo more invasive biopsies than needed to obtain a [8] A. Khachekian, S. Shargh, and S. Arabian, “Pulmonary lym- diagnosis, such as surgical lung biopsies, due to the resem- phangitic carcinomatosis from metastatic gastric adenocarci- blance to ILD in CT scans. However, the limited therapeu- noma: case report,” The Journal of the American Osteopathic tic options available for ILDs prevent many patients from Association, vol. 115, no. 5, pp. 332–337, 2015. undergoing a diagnostic biopsy as the diagnostic proce- [9] A. Biswas, S. Lulu, and P. S. Sriram, “The great masquerader dures are considered to be too risky by their pulmonolo- strikes again!,” The American Journal of Medicine, vol. 130, gist [24]. Therefore, this practice can place patients at no. 7, pp. e303–e304, 2017. the risk of not getting diagnosed for a lethal condition [10] Ö. Dikis, S. Dulger, T. Yildiz, and S. Atahan, “Signet ring cell while getting empirically treated for ILD. gastric carcinoma case diagnosed with pulmonary lymphangi- ILD is more prevalent than PLC. Therefore, due to the tic carcinomatosis,” Clinics in Surgery, vol. 2, no. 1676, p. 2, similarity in presentation, clinicians will first seek and inves- tigate the diagnosis of ILD [25] [26], hence being misled. [11] “Pulmonary lymphangitic carcinomatosis as a primary mani- Interestingly, the misdiagnosis of PLC occurs with an even festation of gastric signet ring cell-type adenocarcinoma in a less common disease entity, i.e., Erdheim–Chester disease, middle-aged woman: a case report,” May 2019, https:// which is presented as PLC [27]. Erdheim–Chester disease insights.ovid.com/chest/chst/2016/04/001/pulmonary- is a rare disease listed under National Organization for lymphangitic-carcinomatosis-primary/268/00002953. Rare Disorders. Thus, there is precedence for the misdiag- [12] G. S and B. S, “When malignancies mimic interstitial lung dis- nosis of PLC, not only with ILD but also other conditions, ease: a case series and review of the literature,” Journal of Clin- warranting robust investigations to enable definite conclu- ical Respiratory Diseases and Care, vol. 1, no. 1, 2015. sions to be made. [13] J. B. Gleason, J. Dolan, and A. Hadeh, “Lymphangitic pulmo- nary metastasis: a rare finding in gastric carcinoma,” Journal of Clinical and Diagnostic Research, vol. 11, no. 5, p. OJ01, Conflicts of Interest The authors declare that they have no conflicts of interest. [14] K. Moubax, W. Wuyts, V. Vandecaveye, and H. Prenen, “Pul- monary lymphangitic carcinomatosis as a primary manifesta- tion of gastric carcinoma in a young adult: a case report and Acknowledgments review of the literature,” BMC Research Notes, vol. 5, no. 1, p. 638, 2012. The pictures of pathology slides were provided by the [15] M. Agca, F. Tokgoz Akyil, M. Hormet et al., “A rare case of Department of Pathology, Benefis Medical Center, Great progressive dyspnea and bilateral lung infiltration in a young Falls, MT. male,” Turkish Thoracic Journal, vol. 18, no. 3, pp. 96–99, References [16] S. Casallo Blanco, F. Marcos Sánchez, S. L. de Matías, A. Viana Alonso, J. Celdrán Gil, and C. E. Núñez, “Lung adenocarci- [1] J. H. Kong, J. Lee, C.-A. Yi et al., “Lung metastases in metasta- noma feigning an interstitial lung disease in a 30-year-old tic gastric cancer: pattern of lung metastases and clinical out- man,” Anales de medicina interna (Madrid, Spain: 1984), come,” Gastric Cancer, vol. 15, no. 3, pp. 292–298, 2012. vol. 24, no. 6, pp. 289–291, 2007. [2] T. Johkoh, J. Ikezoe, N. Tomiyama et al., “CT findings in lym- [17] D. W. Mapel, R. H. Fei, and R. E. Crowell, “Adenocarcinoma phangitic carcinomatosis of the lung: correlation with histo- of the lung presenting as a diffuse interstitial process in a 25- logic findings and pulmonary function tests,” American year-old man,” Lung Cancer, vol. 15, no. 2, pp. 239–244, 1996. Journal of Roentgenology, vol. 158, no. 6, pp. 1217–1222, 1992. [18] O. Cohen, L. Leibovici, and A. I. Wysenbeek, “Carcinoma of [3] E. Dinkel, E. Meyer, A. Mundinger, A. Helwig, U. Blum, and the prostate presenting as interstitial lung disease,” Respira- G. Würtemberger, “Interstitial cancerous lung diseases. Lym- tion, vol. 51, no. 2, pp. 158–160, 2004. phangiosis carcinomatosa and leukemic pulmonary infil- [19] A. R. Jensen, J. Mainz, and J. Overgaard, “Impact of delay on trates,” Der Radiologe, vol. 30, no. 12, pp. 591–597, 1991. diagnosis and treatment of primary lung cancer,” Acta Oncolo- [4] C. Bergin, V. Roggli, C. Coblentz, and C. Chiles, “The second- gica, vol. 41, no. 2, pp. 147–152, 2009. ary pulmonary lobule: normal and abnormal CT appear- [20] GIVIO (Interdisciplinary Group for Cancer Evaluation), ances,” American Journal of Roentgenology, vol. 151, no. 1, “Diagnosis and first-line treatment of patients with lung can- pp. 21–25, 1988. cer in Italian general hospitals,” Tumori Journal, vol. 75, [5] F. J. Gilchrist, H. Alton, M.-A. Brundler, L. Edwards, no. 2, pp. 163–167, 1989. A. Plunkett, and S. Rao, “Pulmonary lymphangitic carcinoma- tosis presenting as severe interstitial lung disease in a 15-year- [21] Cancer of the Lung and Bronchus-Cancer Stat FactsSEERMay 2019, https://seer.cancer.gov/statfacts/html/lungb.html. old female,” European Respiratory Review, vol. 20, no. 121, pp. 208–210, 2011. [22] R. J. Lentz, A. C. Argento, T. V. Colby, O. B. Rickman, and [6] J. Vanclaire, E. Bodart, P. Schlesser, N. Francotte, G. Thiry, and F. Maldonado, “Transbronchial cryobiopsy for diffuse paren- H. Hainaut, “Pulmonary carcinomatous lymphangitis and chymal lung disease: a state-of-the-art review of procedural renal adenocarcinoma,” Archives françaises de pédiatrie, techniques, current evidence, and future challenges,” Journal vol. 47, pp. 735-736, 1991. of Thoracic Disease, vol. 9, no. 7, pp. 2186–2203, 2017. Case Reports in Oncological Medicine 7 [23] C. Ravaglia, M. Bonifazi, A. U. Wells et al., “Safety and diag- nostic yield of transbronchial lung cryobiopsy in diffuse paren- chymal lung diseases: a comparative study versus video- assisted thoracoscopic lung biopsy and a systematic review of the literature,” Respiration, vol. 91, no. 3, pp. 215–227, 2016. [24] Q. Luo, Q. Han, X. Chen, J. Xie, L. Wu, and R. Chen, “The diagnosis efficacy and safety of video-assisted thoracoscopy surgery (VATS) in undefined interstitial lung diseases: a retro- spective study,” Journal of Thoracic Disease, vol. 5, no. 3, pp. 283–288, 2013. [25] D. B. Coultas, R. E. Zumwalt, W. C. Black, and R. E. Sobonya, “The epidemiology of interstitial lung diseases,” American Journal of Respiratory and Critical Care Medicine, vol. 150, no. 4, pp. 967–972, 1994. [26] M. Sakuma, S. Fukui, M. Nakamura et al., “Cancer and pulmo- nary embolism: thrombotic embolism, tumor embolism, and tumor invasion into a large vein,” Circulation Journal, vol. 70, no. 6, pp. 744–749, 2006. [27] S.-A. Yahng, H. H. Kang, S. K. Kim et al., “Erdheim-Chester disease with lung involvement mimicking pulmonary lym- phangitic carcinomatosis,” The American Journal of the Medi- cal Sciences, vol. 337, no. 4, pp. 302–304, 2009. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation

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Copyright © 2020 Swati Pandey and Shishir Ojha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 4150924, 7 pages https://doi.org/10.1155/2020/4150924 Case Report Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation 1 2 Swati Pandey and Shishir Ojha Elkhart General Hospital, 600 East Blvd, Elkhart, IN 46514, USA Elkhart General Hospital, Beacon Medical Group Pulmonology, 500 Arcade Avenue, Suite 210, Elkhart, IN 46514, USA Correspondence should be addressed to Shishir Ojha; ojha_sh@yahoo.com Received 15 May 2019; Accepted 26 October 2019; Published 24 November 2020 Academic Editor: Jose I. Mayordomo Copyright © 2020 Swati Pandey and Shishir Ojha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The diagnosis of lymphangitic carcinomatosis is challenging due to the manifestation of nonspecific symptoms and radiographic abnormalities that bear similarity to those of interstitial lung disease. Herein, we report the case of a 53-year-old woman diagnosed with lymphangitic carcinomatosis from metastatic gastric adenocarcinoma, 3 months after her initial presentation. 1. Case Laboratory findings were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies. A 53-year-old female was referred to the pulmonary clinic Video-assisted thoracic surgical biopsy and transbronchial due to cough and chest pressure for the past 3 months, dur- cryobiopsy were discussed, and the risks and benefits of each ing which several chest X-rays and a computed tomography procedure were explained. She chose to undergo a transbron- (CT) scan of the chest were taken. She was initially expecto- chial cryobiopsy, which was performed 3 months after her rating green sputum; however, the sputum production initial presentation to PCP. Three cryobiopsy samples were reduced after she received antibiotics from her primary care obtained—two from the lateral basal segment and one from physician (PCP). Additionally, she received two courses of the posterior basal segment of the right lower lobe—for path- steroids from visits to the emergency department, which sta- ologic evaluation. Additionally, four forceps biopsy samples bilized her cough. The patient also had occasional symptoms were collected—two each from anterior basal and superior of postprandial bloating. segment of the right lower lobe—for microbiological evalua- She was a lifelong nonsmoker, who worked in farms and tion. The pathology samples were sent to a tertiary care denied any exposure to molds or pets. During examination, center to be reviewed by a pulmonary pathologist with exper- she was afebrile with an oxygen saturation of 87% on room tise in ILD. air inhalation. Her physical exam revealed coarse breath Based on the morphology, the patient was diagnosed with sounds on auscultation and decreased breath sounds at the a tumor that was characterized as metastatic adenocarci- level of the left lung base posteriorly. A CT scan of her chest noma with lymphangitic spread (Figures 2 and 3). Tumor (Figure 1) showed bilateral linear coarse reticulations with no cells were positive for keratin and negative for CD31, thus peripheral predilection or ground-glass opacities and a small confirming the diagnosis. A second round of histological amount of left pleural effusion; the abdomen did not show staining was negative for thyroid transcription factor-1, any abnormality in the CT scan. Based on her symptoms GATA 3, mammaglobin, and gross cystic disease fluid and chest CT findings, we suspected a diagnosis of interstitial protein-15 (GCDFP-15), thereby excluding the lungs and lung disease (ILD). breast as primaries. As CDX2 was strongly positive, gastric 2 Case Reports in Oncological Medicine Figure 1: Chest CT scan. Figure 2: Hematoxylin and eosin-stained slide of cryobiopsy of lung. Arrow pointing to lymph-vascular invasion of tumor cells. primary was suspected. The differential diagnosis in the Thereafter, the patient underwent a repeat CT scan of the upper gastrointestinal primary or pancreatobiliary primary abdomen and pelvis, which did not reveal any mass or abnor- at this stage of staining supported the assumption. mality to suggest a primary. Three weeks after the Case Reports in Oncological Medicine 3 Figure 3: Hematoxylin and eosin-stained slide of cryobiopsy of lung. Arrow pointing to adenocarcinoma. bronchoscopic biopsy, she underwent an upper endoscopy, of this rare pattern, accounting for only 26.4% of pulmonary which revealed an ulcerated gastric mass occupying the car- metastasis [1]. Gastric lesions or abnormality in other viscera dia and antrum of the stomach. Biopsies from the mass were absent on the CT scan of the abdomen. Her chest CT revealed moderate to poorly differentiated invasive adeno- revealed interlobular septal thickening. The absence of medi- astinal or hilar lymph node enlargement and lung masses or carcinoma with lymphovascular invasion (Figure 4). Two days after the endoscopic biopsies, the patient was nodules excluded a diagnosis of malignancy. Despite wide- seen by an oncologist in an outpatient setting where several spread pulmonary parenchymal abnormalities, there was chemotherapy options ranging from aggressive regimens, no lymph node involvement. Mediastinal or hilar lymph- such as FOLFOX, to the least aggressive 5 FU with leucovorin adenopathy is commonly seen with lymphangitic spread were discussed. However, the patient declined the treatment. [2], but lymph node involvement is not essential. The Subsequently, she was hospitalized three times, 2 weeks mechanism of lymphangitic spread is hematogenous apart, for worsening dyspnea and was treated with thoracent- tumor embolism to the lungs and rarely due to contiguous esis on each occasion. During her last admissions, a chest lymphangitic spread [3]. tube was placed due to iatrogenic pneumothorax after thora- The diagnosis of metastatic cancer with pulmonary carci- centesis. The patient experienced worsening dyspnea and nomatosis is often delayed by months from the onset of hypoxemia, and comfort measures were initiated. The symptoms and imaging studies. This delay is mainly due to patient died 10 days after the last hospitalization, about 2 two attributes that are strongly associated with its presenta- months after her diagnosis. tion and imaging studies. First, patient characteristics play an important role. Most patients present with dry cough and dyspnea due to pulmonary parenchymal involvement, 2. Discussion irrespective of the origin of the primary. Hence, the workup We report the case of occult gastric malignancy with pulmo- for the symptoms is performed and does not involve imaging nary lymphangitic carcinomatosis (PLC). or diagnostic tests, which can reveal the primary. A patient’s Pulmonary metastasis is rare with gastric cancer, repre- age is usually less than that of a typical lung cancer patient because a wide variety of cancers that occur at a young age senting less than one percent of distant metastasis. The most commonly seen pattern of pulmonary metastasis is hematog- may present with lymphangitic spread. Patients are often enous which accounts for 52.3%, followed by pleural metas- nonsmokers, thereby lowering the suspicion for lung cancer. tasis (35.2%), and lymphangitic spread is the least common Moreover, patients are often empirically treated with 4 Case Reports in Oncological Medicine Figure 4: Hematoxylin and eosin-stained slide of Gastric Biopsy: arrow pointing to gastric adenocarcinoma. The reason for the delay in the diagnosis of PLC can be antibiotics for presumed respiratory tract infection and inhalers for dyspnea. due to the misinterpretation of the presentation and radio- Second, a radiologist is often misled by imaging patterns, graphic abnormality by the treating physician, and such whether on chest X-ray or chest CT, and the requesting phy- delay reduces patients’ duration of survival after diagnosis. sician may be convinced of an ILD diagnosis. The CT pattern Compounding this grave situation is that patients spend their of PLC is very similar to that of many ILDs, including sar- remaining life under intensive care while undergoing inva- coidosis, which is an arduous task to differentiate. Subtle dif- sive procedures to diagnose what was misinterpreted as ferences do exist, but these are not easy to spot and include a ILD. The overall 5-year survival rate for lung cancer for all great involvement of the interlobular septa and interstitium stages is 19.4% [21]. In comparison, as depicted in the table, in PLC and more distortion of secondary pulmonary lobule several diagnoses of PLC occurred in the intensive care unit due to fibrosis in sarcoid [4]. Thus, owing to the clinical pre- on vented patients, and most of them died within a day to sentation and radiographic patterns, our focus was on the few weeks thereafter. diagnosis of an underlying primary pulmonary parenchymal The misinterpretation of PLC as an ILD is more likely to occur if the imaging study shows findings of only pulmonary disease, specifically an ILD, rather than casting a wider net, which would have included an examination for malignancy. carcinomatosis, i.e., only interstitial changes, which are very We performed a literature search using the PubMed data- similar to many ILDs, without lung mass or a nodule. base for studies reporting cases of lymphangitic carcinomato- Although many ILDs present with lymph node enlargement, sis that were suspected as an ILD by treating physicians. The the presence of mediastinal or hilar lymph node enlargement raises the suspicion of malignancy. extracted publications are listed in Table 1 [5–18]. Informa- tion on the types of delays that occurred in the case reports The patient in this case report did not have mediastinal or are listed (Table 1), which included time interval from the hilar lymphadenopathy, unlike most patients with pulmo- first occurrence of a symptom to the first contact with a phy- nary carcinomatosis who have lymphadenopathy. If medias- sician and the interval from symptoms onset, diagnosis, and tinal or hilar lymphadenopathy were present, then a much more conservative approach, such as biopsy of the lymph presentation to death. Delays in the diagnosis of primary lung cancer diagnosis node with endobronchial ultrasound with or without trans- range from 7 days to 6 months and from onset of symptoms bronchial forceps biopsy, would have been considered. to contact with a physician [19]. The largest trial that has Instead, due to the presentation, a much more invasive investigated 380 consecutive patients with primary lung can- approach than needed for the diagnosis of malignancy, such as transbronchial cryobiopsy, was undertaken. Transbron- cer found that the median duration from the onset of symp- toms to visit with a physician was 7 days, that from the chial cryobiopsy is a new technique that enables pulmonolo- physician’s visit to diagnosis was 31 days, and that from gists to obtain a larger specimen than the traditional symptom onset to diagnosis was 50 days [20]. As depicted, transbronchial forceps biopsy [22], but whether it can serve the wait times are similar to the delays in the diagnosis of pri- as an alternative to surgical biopsy for the diagnosis of ILDs is a subject of investigation. Nevertheless, the risks of mary lung cancer. Case Reports in Oncological Medicine 5 Table 1: Case reports of PLC suspected as an ILD. S. NO 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 7 31 45 53 63 62 62 39 24 30 30 25 62 Age/gender F M F F F M F M F M M M M M Cough, Progressive Dry cough, night Dry cough, night Dyspnea, dry sob, lethargy, Respiratory Productive cough Progressive dyspnea, Worsening Dyspnea, dry Cough, sob, fever, Cough, dyspnea Symptoms Dry cough, dyspnea Dry cough dyspnea and sweats, dyspnea sweats, dyspnea on cough fever for satiety, distress and dyspnea weight loss, and rash. dyspnea cough. and chest pain. on exertion cough hemoptysis exertion, weight loss six weeks anorexia Mediastinal Enlarged med Subpleural Interstitial and Interstitial Diffuse Ground glass opacities, Thickening of Mediastinal Mediastinal lymphadenopathy. Interlobular septal LN, diffuse reticulations ground-glass thickening, crazy reticulonodular and diffusely thickened peribronchovascular, lymphadenopathy Diffuse Bilateral opacities. Thickened lymphadenopathy, Thickened thickening, scattered reticular pulmonary Chest CT paving, ground-glass interlobular septa, interstitial, and and interstitial interstitial interlobular septa B/l interstitial interlobular septa, GGO, nodularity along thickening, nodules, Borderline mediastinal opacities, pleural mediastinal and hilar interlobular septa. reticulonodular prominence infiltrates infiltrates ground-glass fissures, reticular-nodular enlarged mediastinal lymphadenopathy effusions LN enlarged Ground glass opacities interstitial pattern. opacities pattern. mediastinal LN lymphadenopathy Bronchoscopy Bronchoalveolar Bronchoalveolar Bronchoalveolar Bronchoalveolar could not be lavage. Central lavage showed atypical Transbronchial Transbronchial Bronchoalveolar Transbronchial lavage negative, lavage and VATS surgical completed. Open lung Diagnostics Open lung biopsy Open lung biopsy Open lung biopsy bronchoscopic cells. Transbronchial biopsy, prostate biopsy lavage biopsy cervical skin biopsy transbronchial biopsy Diagnosed by biopsy biopsies. Gastric origin biopsies could not be biopsy positive biopsy surgical lung by EGD. done. biopsy Signet ring Gastric Signet ring cell gastric Adenocarcinoma Renal Adenocarcinoma of Signet ring gastric Signet ring gastric Pulmonary Gastric Pulmonary Pulmonary Prostate Diagnosis Melanoma gastric adenocarcinoma with adenocarcinoma on unknown primary adenocarcinoma colon adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma adenocarcinoma signet ring. EGD biopsy adenocarcinoma focal Symptom onset to 107 NA 180 117 Over 30 days 150 180 NA NA 60 60 NA 379 42 diagnosis (days) Symptom to 108 NA 191 119 NA 159 180 NA NA NA NA NA 382 NA death (days) Presentation to death 70 NA 16 29 NA NA 67 NA NA NA NA NA 17 NA (days) Diagnosis to 1NA 11 12 NA 7 7 NA NA NA NA NA 3 NA death (days) Prednisone, Ciprofloxacin and clarithromycin, erythromycin for Piperacillin- Therapy Steroids for Vancomycin and Broad-spectrum salbutamol, bronchitis, right heart Antibiotics and Immunosuppressive tazobactam, Not applicable. prior to NA sarcoidosis. Folfox piperacillin- NA Steroids antibiotics for 14 days, NA Antibiotics. antitubercular, Cath, sildenafil, and steroids therapy ciprofloxacin, and Survived. diagnosis after diagnosis tazobactam high dose steroids antipneumocystis ambrisentan for Pulm oseltamivir therapy. HTN. ICU. Biopsy while Setting of Post biopsy, ICU, ICU on vent ICU vent NA intubated, palliative Non-ICU setting NA Not in ICU NA NA Na NA ICU NA diagnosis vent support postdiagnosis Contralateral Abdominal wall, tibia, Thoracic and pulmonary and Lung, pleura, right ribs, Metastasis Not available (NA) NA femur, right humerus, NA NA Skin NA NA NA NA NA lumbar spine spinal right iliac bone lumbar spine metastasis. Guler et al. [12], Gleason et al., J of Vanclaire et al., Biswas et al., Am Dikis et al., Journal of Mapel et al., Cohen et al. Gilchrist et al., Eur Thomas and Lenox, Khachekian et al., J Am Wang et al., Poster, clinical and Moubax et al., BMC Meltem et al., Turkish Blanco et al., An Author Arch Fr Pediatrics Journal of Clinics in Surgery clinical Lung Cancer [18], Resp Review [5] CMAJ [7] Osteopath Assoc. 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