Case Reports in Oncological Medicine

Case Reports in Oncological Medicine / 2020 / Article

Case Report | Open Access

Volume 2020 |Article ID 4150924 | https://doi.org/10.1155/2020/4150924

Swati Pandey, Shishir Ojha, "Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation", Case Reports in Oncological Medicine, vol. 2020, Article ID 4150924, 7 pages, 2020. https://doi.org/10.1155/2020/4150924

Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation

Academic Editor: Jose I. Mayordomo
Received15 May 2019
Accepted26 Oct 2019
Published24 Nov 2020

Abstract

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

A 53-year-old female was referred to the pulmonary clinic due to cough and chest pressure for the past 3 months, during which several chest X-rays and a computed tomography (CT) scan of the chest were taken. She was initially expectorating green sputum; however, the sputum production reduced after she received antibiotics from her primary care physician (PCP). Additionally, she received two courses of steroids from visits to the emergency department, which stabilized her cough. The patient also had occasional symptoms of postprandial bloating.

She was a lifelong nonsmoker, who worked in farms and denied any exposure to molds or pets. During examination, she was afebrile with an oxygen saturation of 87% on room air inhalation. Her physical exam revealed coarse breath sounds on auscultation and decreased breath sounds at the level of the left lung base posteriorly. A CT scan of her chest (Figure 1) showed bilateral linear coarse reticulations with no peripheral predilection or ground-glass opacities and a small amount of left pleural effusion; the abdomen did not show any abnormality in the CT scan. Based on her symptoms and chest CT findings, we suspected a diagnosis of interstitial lung disease (ILD).

Laboratory findings were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies. Video-assisted thoracic surgical biopsy and transbronchial cryobiopsy were discussed, and the risks and benefits of each procedure were explained. She chose to undergo a transbronchial cryobiopsy, which was performed 3 months after her initial presentation to PCP. Three cryobiopsy samples were obtained—two from the lateral basal segment and one from the posterior basal segment of the right lower lobe—for pathologic evaluation. Additionally, four forceps biopsy samples were collected—two each from anterior basal and superior segment of the right lower lobe—for microbiological evaluation. The pathology samples were sent to a tertiary care center to be reviewed by a pulmonary pathologist with expertise in ILD.

Based on the morphology, the patient was diagnosed with a tumor that was characterized as metastatic adenocarcinoma with lymphangitic spread (Figures 2 and 3). Tumor cells were positive for keratin and negative for CD31, thus confirming the diagnosis. A second round of histological staining was negative for thyroid transcription factor-1, GATA 3, mammaglobin, and gross cystic disease fluid protein-15 (GCDFP-15), thereby excluding the lungs and breast as primaries. As CDX2 was strongly positive, gastric primary was suspected. The differential diagnosis in the upper gastrointestinal primary or pancreatobiliary primary at this stage of staining supported the assumption.

Thereafter, the patient underwent a repeat CT scan of the abdomen and pelvis, which did not reveal any mass or abnormality to suggest a primary. Three weeks after the bronchoscopic biopsy, she underwent an upper endoscopy, which revealed an ulcerated gastric mass occupying the cardia and antrum of the stomach. Biopsies from the mass revealed moderate to poorly differentiated invasive adenocarcinoma with lymphovascular invasion (Figure 4).

Two days after the endoscopic biopsies, the patient was seen by an oncologist in an outpatient setting where several chemotherapy options ranging from aggressive regimens, such as FOLFOX, to the least aggressive 5 FU with leucovorin were discussed. However, the patient declined the treatment. Subsequently, she was hospitalized three times, 2 weeks apart, for worsening dyspnea and was treated with thoracentesis on each occasion. During her last admissions, a chest tube was placed due to iatrogenic pneumothorax after thoracentesis. The patient experienced worsening dyspnea and hypoxemia, and comfort measures were initiated. The patient died 10 days after the last hospitalization, about 2 months after her diagnosis.

2. Discussion

We report the case of occult gastric malignancy with pulmonary lymphangitic carcinomatosis (PLC).

Pulmonary metastasis is rare with gastric cancer, representing less than one percent of distant metastasis. The most commonly seen pattern of pulmonary metastasis is hematogenous which accounts for 52.3%, followed by pleural metastasis (35.2%), and lymphangitic spread is the least common of this rare pattern, accounting for only 26.4% of pulmonary metastasis [1]. Gastric lesions or abnormality in other viscera were absent on the CT scan of the abdomen. Her chest CT revealed interlobular septal thickening. The absence of mediastinal or hilar lymph node enlargement and lung masses or nodules excluded a diagnosis of malignancy. Despite widespread pulmonary parenchymal abnormalities, there was no lymph node involvement. Mediastinal or hilar lymphadenopathy is commonly seen with lymphangitic spread [2], but lymph node involvement is not essential. The mechanism of lymphangitic spread is hematogenous tumor embolism to the lungs and rarely due to contiguous lymphangitic spread [3].

The diagnosis of metastatic cancer with pulmonary carcinomatosis is often delayed by months from the onset of symptoms and imaging studies. This delay is mainly due to two attributes that are strongly associated with its presentation and imaging studies. First, patient characteristics play an important role. Most patients present with dry cough and dyspnea due to pulmonary parenchymal involvement, irrespective of the origin of the primary. Hence, the workup for the symptoms is performed and does not involve imaging or diagnostic tests, which can reveal the primary. A patient’s age is usually less than that of a typical lung cancer patient because a wide variety of cancers that occur at a young age may present with lymphangitic spread. Patients are often nonsmokers, thereby lowering the suspicion for lung cancer. Moreover, patients are often empirically treated with antibiotics for presumed respiratory tract infection and inhalers for dyspnea.

Second, a radiologist is often misled by imaging patterns, whether on chest X-ray or chest CT, and the requesting physician may be convinced of an ILD diagnosis. The CT pattern of PLC is very similar to that of many ILDs, including sarcoidosis, which is an arduous task to differentiate. Subtle differences do exist, but these are not easy to spot and include a great involvement of the interlobular septa and interstitium in PLC and more distortion of secondary pulmonary lobule due to fibrosis in sarcoid [4]. Thus, owing to the clinical presentation and radiographic patterns, our focus was on the diagnosis of an underlying primary pulmonary parenchymal disease, specifically an ILD, rather than casting a wider net, which would have included an examination for malignancy.

We performed a literature search using the PubMed database for studies reporting cases of lymphangitic carcinomatosis that were suspected as an ILD by treating physicians. The extracted publications are listed in Table 1 [518]. Information on the types of delays that occurred in the case reports are listed (Table 1), which included time interval from the first occurrence of a symptom to the first contact with a physician and the interval from symptoms onset, diagnosis, and presentation to death.


S. NO1234567891011121314
Age/gender15
F
7
M
31
F
45
F
53
F
63
M
62
F
62
M
39
F
24
M
30
M
30
M
25
M
62
M
SymptomsCough, sob, lethargy, satiety, anorexiaRespiratory distressDry cough, dyspneaDry coughProductive cough and dyspneaProgressive dyspnea and coughProgressive dyspnea, weight loss, and rash.Worsening dyspneaDyspnea, dry cough.Dry cough, night sweats, dyspnea hemoptysisDry cough, night sweats, dyspnea on exertion, weight lossCough, sob, fever, and chest pain.Cough, dyspnea on exertionDyspnea, dry cough fever for six weeks
Chest CTThickened interlobular septaMediastinal lymphadenopathy, B/l interstitial infiltratesMediastinal lymphadenopathy. Thickened interlobular septa, ground-glass opacitiesInterlobular septal thickening, scattered GGO, nodularity along fissures,Interstitial thickening, crazy paving, mediastinal lymphadenopathyEnlarged med LN, diffuse reticular thickening, reticular-nodular pattern.Diffuse reticulonodular and ground-glass opacities, pleural effusionsSubpleural reticulations pulmonary nodules, enlarged mediastinal LNInterstitial and ground-glass opacities. Borderline mediastinal lymphadenopathyGround glass opacities, diffusely thickened interlobular septa, mediastinal and hilar LN enlargedThickening of peribronchovascular, interstitial, and interlobular septa. Ground glass opacitiesMediastinal lymphadenopathy and reticulonodular interstitial pattern.Diffuse interstitial prominenceBilateral interstitial infiltrates
DiagnosticsOpen lung biopsyOpen lung biopsyTransbronchial biopsyOpen lung biopsyBronchoalveolar lavageTransbronchial biopsyBronchoalveolar lavage negative, cervical skin biopsy positiveBronchoalveolar lavage and transbronchial biopsyVATS surgical biopsyBronchoalveolar lavage. Central bronchoscopic biopsies. Gastric origin by EGD.Bronchoalveolar lavage showed atypical cells. Transbronchial biopsies could not be done.Bronchoscopy could not be completed. Diagnosed by surgical lung biopsyOpen lung biopsyTransbronchial biopsy, prostate biopsy
DiagnosisAdenocarcinoma unknown primaryRenal adenocarcinomaAdenocarcinoma of colonSignet ring gastric adenocarcinomaMelanomaSignet ring gastric adenocarcinomaSignet ring gastric adenocarcinomaPulmonary adenocarcinomaGastric adenocarcinomaGastric adenocarcinoma with focal signet ring.Signet ring cell gastric adenocarcinoma on EGD biopsyPulmonary adenocarcinomaPulmonary adenocarcinomaProstate adenocarcinoma
Symptom onset to diagnosis (days)107NA180117Over 30 days150180NANA6060NA37942
Symptom to death (days)108NA191119NA159180NANANANANA382NA
Presentation to death (days)70NA1629NANA67NANANANANA17NA
Diagnosis to death (days)1NA1112NA77NANANANANA3NA
Therapy prior to diagnosisPrednisone, clarithromycin, salbutamol, antitubercular, antipneumocystis therapy.NASteroids for sarcoidosis. Folfox after diagnosisCiprofloxacin and erythromycin for bronchitis, right heart Cath, sildenafil, and ambrisentan for Pulm HTN.Vancomycin and piperacillin-tazobactamAntibiotics and steroidsImmunosuppressive therapyNASteroidsBroad-spectrum antibiotics for 14 days, high dose steroidsPiperacillin-tazobactam, ciprofloxacin, and oseltamivirNAAntibiotics.Not applicable. Survived.
Setting of diagnosisICU ventNAPost biopsy, ICU, ventICU. Biopsy while intubated, palliative postdiagnosisNon-ICU settingICU on vent supportNANot in ICUNANANaNAICUNA
MetastasisNot available (NA)NAThoracic and lumbar spineAbdominal wall, tibia, femur, right humerus, lumbar spineNANASkinContralateral pulmonary and spinal metastasis.NALung, pleura, right ribs, right iliac boneNANANANA
AuthorGilchrist et al., Eur Resp Review [5]Vanclaire et al., Arch Fr Pediatrics [6]Thomas and Lenox, CMAJ [7]Khachekian et al., J Am Osteopath Assoc. [8]Biswas et al., Am Journal of Medicine [9]Dikis et al., Clinics in Surgery [10]Wang et al., Poster, chest meeting [11]Guler et al. [12], Journal of clinical respiratory disease & care.Gleason et al., J of clinical and diagnostic research [13]Moubax et al., BMC research notes [14]Meltem et al., Turkish thoracic journal [15]Blanco et al., An Med Interna [16]Mapel et al.,
Lung Cancer [17]
Cohen et al. [18],
Respiration

Delays in the diagnosis of primary lung cancer diagnosis range from 7 days to 6 months and from onset of symptoms to contact with a physician [19]. The largest trial that has investigated 380 consecutive patients with primary lung cancer found that the median duration from the onset of symptoms to visit with a physician was 7 days, that from the physician’s visit to diagnosis was 31 days, and that from symptom onset to diagnosis was 50 days [20]. As depicted, the wait times are similar to the delays in the diagnosis of primary lung cancer.

The reason for the delay in the diagnosis of PLC can be due to the misinterpretation of the presentation and radiographic abnormality by the treating physician, and such delay reduces patients’ duration of survival after diagnosis. Compounding this grave situation is that patients spend their remaining life under intensive care while undergoing invasive procedures to diagnose what was misinterpreted as ILD. The overall 5-year survival rate for lung cancer for all stages is 19.4% [21]. In comparison, as depicted in the table, several diagnoses of PLC occurred in the intensive care unit on vented patients, and most of them died within a day to few weeks thereafter.

The misinterpretation of PLC as an ILD is more likely to occur if the imaging study shows findings of only pulmonary carcinomatosis, i.e., only interstitial changes, which are very similar to many ILDs, without lung mass or a nodule. Although many ILDs present with lymph node enlargement, the presence of mediastinal or hilar lymph node enlargement raises the suspicion of malignancy.

The patient in this case report did not have mediastinal or hilar lymphadenopathy, unlike most patients with pulmonary carcinomatosis who have lymphadenopathy. If mediastinal or hilar lymphadenopathy were present, then a much more conservative approach, such as biopsy of the lymph node with endobronchial ultrasound with or without transbronchial forceps biopsy, would have been considered. Instead, due to the presentation, a much more invasive approach than needed for the diagnosis of malignancy, such as transbronchial cryobiopsy, was undertaken. Transbronchial cryobiopsy is a new technique that enables pulmonologists to obtain a larger specimen than the traditional transbronchial forceps biopsy [22], but whether it can serve as an alternative to surgical biopsy for the diagnosis of ILDs is a subject of investigation. Nevertheless, the risks of pneumothorax and bleeding are higher than those of forceps biopsy [23], but the overall morbidity is lower than that of surgical lung biopsy [23]. Therefore, patients with PLC undergo more invasive biopsies than needed to obtain a diagnosis, such as surgical lung biopsies, due to the resemblance to ILD in CT scans. However, the limited therapeutic options available for ILDs prevent many patients from undergoing a diagnostic biopsy as the diagnostic procedures are considered to be too risky by their pulmonologist [24]. Therefore, this practice can place patients at the risk of not getting diagnosed for a lethal condition while getting empirically treated for ILD.

ILD is more prevalent than PLC. Therefore, due to the similarity in presentation, clinicians will first seek and investigate the diagnosis of ILD [25] [26], hence being misled. Interestingly, the misdiagnosis of PLC occurs with an even less common disease entity, i.e., Erdheim–Chester disease, which is presented as PLC [27]. Erdheim–Chester disease is a rare disease listed under National Organization for Rare Disorders. Thus, there is precedence for the misdiagnosis of PLC, not only with ILD but also other conditions, warranting robust investigations to enable definite conclusions to be made.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

The pictures of pathology slides were provided by the Department of Pathology, Benefis Medical Center, Great Falls, MT.

References

  1. J. H. Kong, J. Lee, C.-A. Yi et al., “Lung metastases in metastatic gastric cancer: pattern of lung metastases and clinical outcome,” Gastric Cancer, vol. 15, no. 3, pp. 292–298, 2012. View at: Publisher Site | Google Scholar
  2. T. Johkoh, J. Ikezoe, N. Tomiyama et al., “CT findings in lymphangitic carcinomatosis of the lung: correlation with histologic findings and pulmonary function tests,” American Journal of Roentgenology, vol. 158, no. 6, pp. 1217–1222, 1992. View at: Publisher Site | Google Scholar
  3. E. Dinkel, E. Meyer, A. Mundinger, A. Helwig, U. Blum, and G. Würtemberger, “Interstitial cancerous lung diseases. Lymphangiosis carcinomatosa and leukemic pulmonary infiltrates,” Der Radiologe, vol. 30, no. 12, pp. 591–597, 1991. View at: Google Scholar
  4. C. Bergin, V. Roggli, C. Coblentz, and C. Chiles, “The secondary pulmonary lobule: normal and abnormal CT appearances,” American Journal of Roentgenology, vol. 151, no. 1, pp. 21–25, 1988. View at: Publisher Site | Google Scholar
  5. F. J. Gilchrist, H. Alton, M.-A. Brundler, L. Edwards, A. Plunkett, and S. Rao, “Pulmonary lymphangitic carcinomatosis presenting as severe interstitial lung disease in a 15-year-old female,” European Respiratory Review, vol. 20, no. 121, pp. 208–210, 2011. View at: Publisher Site | Google Scholar
  6. J. Vanclaire, E. Bodart, P. Schlesser, N. Francotte, G. Thiry, and H. Hainaut, “Pulmonary carcinomatous lymphangitis and renal adenocarcinoma,” Archives françaises de pédiatrie, vol. 47, pp. 735-736, 1991. View at: Google Scholar
  7. A. Thomas and R. Lenox, “Pulmonary lymphangitic carcinomatosis as a primary manifestation of colon cancer in a young adult,” Canadian Medical Association Journal, vol. 179, no. 4, pp. 338–340, 2008. View at: Publisher Site | Google Scholar
  8. A. Khachekian, S. Shargh, and S. Arabian, “Pulmonary lymphangitic carcinomatosis from metastatic gastric adenocarcinoma: case report,” The Journal of the American Osteopathic Association, vol. 115, no. 5, pp. 332–337, 2015. View at: Publisher Site | Google Scholar
  9. A. Biswas, S. Lulu, and P. S. Sriram, “The great masquerader strikes again!,” The American Journal of Medicine, vol. 130, no. 7, pp. e303–e304, 2017. View at: Publisher Site | Google Scholar
  10. Ö. Dikis, S. Dulger, T. Yildiz, and S. Atahan, “Signet ring cell gastric carcinoma case diagnosed with pulmonary lymphangitic carcinomatosis,” Clinics in Surgery, vol. 2, no. 1676, p. 2, 2017. View at: Google Scholar
  11. “Pulmonary lymphangitic carcinomatosis as a primary manifestation of gastric signet ring cell-type adenocarcinoma in a middle-aged woman: a case report,” May 2019, https://insights.ovid.com/chest/chst/2016/04/001/pulmonary-lymphangitic-carcinomatosis-primary/268/00002953. View at: Google Scholar
  12. G. S and B. S, “When malignancies mimic interstitial lung disease: a case series and review of the literature,” Journal of Clinical Respiratory Diseases and Care, vol. 1, no. 1, 2015. View at: Publisher Site | Google Scholar
  13. J. B. Gleason, J. Dolan, and A. Hadeh, “Lymphangitic pulmonary metastasis: a rare finding in gastric carcinoma,” Journal of Clinical and Diagnostic Research, vol. 11, no. 5, p. OJ01, 2017. View at: Publisher Site | Google Scholar
  14. K. Moubax, W. Wuyts, V. Vandecaveye, and H. Prenen, “Pulmonary lymphangitic carcinomatosis as a primary manifestation of gastric carcinoma in a young adult: a case report and review of the literature,” BMC Research Notes, vol. 5, no. 1, p. 638, 2012. View at: Publisher Site | Google Scholar
  15. M. Agca, F. Tokgoz Akyil, M. Hormet et al., “A rare case of progressive dyspnea and bilateral lung infiltration in a young male,” Turkish Thoracic Journal, vol. 18, no. 3, pp. 96–99, 2017. View at: Publisher Site | Google Scholar
  16. S. Casallo Blanco, F. Marcos Sánchez, S. L. de Matías, A. Viana Alonso, J. Celdrán Gil, and C. E. Núñez, “Lung adenocarcinoma feigning an interstitial lung disease in a 30-year-old man,” Anales de medicina interna (Madrid, Spain: 1984), vol. 24, no. 6, pp. 289–291, 2007. View at: Google Scholar
  17. D. W. Mapel, R. H. Fei, and R. E. Crowell, “Adenocarcinoma of the lung presenting as a diffuse interstitial process in a 25-year-old man,” Lung Cancer, vol. 15, no. 2, pp. 239–244, 1996. View at: Publisher Site | Google Scholar
  18. O. Cohen, L. Leibovici, and A. I. Wysenbeek, “Carcinoma of the prostate presenting as interstitial lung disease,” Respiration, vol. 51, no. 2, pp. 158–160, 2004. View at: Publisher Site | Google Scholar
  19. A. R. Jensen, J. Mainz, and J. Overgaard, “Impact of delay on diagnosis and treatment of primary lung cancer,” Acta Oncologica, vol. 41, no. 2, pp. 147–152, 2009. View at: Publisher Site | Google Scholar
  20. GIVIO (Interdisciplinary Group for Cancer Evaluation), “Diagnosis and first-line treatment of patients with lung cancer in Italian general hospitals,” Tumori Journal, vol. 75, no. 2, pp. 163–167, 1989. View at: Google Scholar
  21. Cancer of the Lung and Bronchus-Cancer Stat Facts, SEER, May 2019, https://seer.cancer.gov/statfacts/html/lungb.html.
  22. R. J. Lentz, A. C. Argento, T. V. Colby, O. B. Rickman, and F. Maldonado, “Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges,” Journal of Thoracic Disease, vol. 9, no. 7, pp. 2186–2203, 2017. View at: Publisher Site | Google Scholar
  23. C. Ravaglia, M. Bonifazi, A. U. Wells et al., “Safety and diagnostic yield of transbronchial lung cryobiopsy in diffuse parenchymal 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. View at: Publisher Site | Google Scholar
  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 retrospective study,” Journal of Thoracic Disease, vol. 5, no. 3, pp. 283–288, 2013. View at: Publisher Site | Google Scholar
  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. View at: Publisher Site | Google Scholar
  26. M. Sakuma, S. Fukui, M. Nakamura et al., “Cancer and pulmonary embolism: thrombotic embolism, tumor embolism, and tumor invasion into a large vein,” Circulation Journal, vol. 70, no. 6, pp. 744–749, 2006. View at: Publisher Site | Google Scholar
  27. S.-A. Yahng, H. H. Kang, S. K. Kim et al., “Erdheim-Chester disease with lung involvement mimicking pulmonary lymphangitic carcinomatosis,” The American Journal of the Medical Sciences, vol. 337, no. 4, pp. 302–304, 2009. View at: Publisher Site | Google Scholar

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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