Long Case
Marc Freiman
Wednesday Pulmonary Conference
August 7, 2013
HPI
 50 yo woman from the Dominican republic presenting to
pulmonary clinic for cough 4-5 years
 Symptoms may have started after a cold
 ? Worse in the summer, no temporal relation to night/day
 Dry, non-productive
 DOE 2-3 city blocks, 2 flights of stairs
 ROS - Denies HA, sinus congestion, heartburn, reflux. Denies
chest pain, palpitations, orthopnea, PND or edema
PMHx/Soc Hx
 Vitiligo
 From DR 3 years ago
 Denies childhood asthma
 Worked in paper shredding
factory for 1 yr
 Currently works in retail
 Never smoker
 No EtOH, illicits
Physical exam
Afeb P 95 130/84 96% RA; BMI 30 (150lbs, 5’)
 General: comfortable
 Clear, no wheeze. ? Crackles at bases bilaterally
 Neck: supple, no masses, neck nodes not palpable
 CV: RRR No m/r/g
 No cervical LAD, neck supple
 No desaturation on exertion
CXR
Symptomatic treatment
 Benadryl
 Chlorpheniramine
Return visit
 Benadryl lets her sleep through the night
 Still with continued cough
 She climbed 3 flights of stairs and became SOB but did not
desaturate - minimal sats 96% HR 120
PFT
PFT
CT Scan
CT read
LUNGS: There are multiple nodules in both lungs
measuring up to 5 mm.
Mosaic attenuation is seen in both lungs most prominent in the
lower lobes suggestive of small airways or small vessel
disease.
Labs
 CBC, Chem 7 wnl
 ANA, RF negative
 TTE unremarkable
Chronic cough
Just kidding…
VATS biopsy
 Had bronchoscopy w BAL
 VATS biopsy for right lung with RML and RLL biopsy
 Nodule palpated in RML
Bronchoscopy and VATS results
 Middle lobe lavage cytology negative
 Aerobic, anaerobic, fungal and AFB cultures negative
 RIGHT LOWER LOBE BIOPSY:
 LUNG PARENCHYMA WITH CONGESTION,
HEMORRHAGE AND HEMOSIDERIN LADEN
MACROPHAGES.
 NO TUMOR IDENTIFIED.
synaptophysin
chromogranin
RML biopsy
 IMMUNOHISTOCHEMICAL STUDIES PERFORMED ON
PARAFFIN EMBEDDED TISSUE (BLOCK A2) SHOWS
POSITIVE STAINING FOR CHROMOGRANIN,
SYNAPTOPHYSINMULTIPLE FOCI OF
NEUROENDOCRINE TUMOR, TUMORLETS/ SMALL
CARCINOID TUMOR.
Diffuse idiopathic pulmonary
neuroendocrine cell hyperplasia
DIPNECH
Overview of bronchopulmonary
neuroendocrine tumors (BP-NET)
 4 types
 Typical carcinoid
 Atypical Carcinoid
 Large cell neuroendocrine carcinoma
 Small cell neuroendocrine carcinoma
Diffuse Idiopathic Pulmonary
Endocrine Cell Hyperplasia (DIPNECH)
 Preneoplastic
 Pulmonary tumorlets (<5mm)
 Had been known to occur in:
 ILD
 Bronchiolitis obliterans
 Patients living at high altitudes
Purpose of the neuroendocrine cell in
the lung?
 Unknown
 Arises from Kulchitsky cell
 Thought to be involved as ‘airway sensors’
 Mediate airway tone, pulmonary circulation, and control of
breathing.
 Act as both chemo and mechanoreceptors
 Also likely involved in development of the lung
AJRCCM - demographics
 Women – 92% (23/25)
 Mean diagnosis 58 years old
 Range 36-76
 67% non-smokers (16/24)
PFTs
PFTs
17%
13%
54%
Obstructive
Restrictive
Mixed
CT findings
 Pulmonary nodules (63%, 15 pts)
 Ground glass (29%, 7 pts)
 Bronchiectasis (21%, 5 pts)
 Mosaic attenuation (17%, 4 pts)
Clinical course – AJRCCM 2011
 92% of patients had symptoms
 Cough, dyspnea, wheezing
 Symptoms lasted between days to years – average 8.6 years
 Widely variable course has been described
 Not clear exactly why some people deteriorate – known to produce bombesin and
fibrinogenic cytokines
 41% (7) stable without clinical deterioration
 Oral predniosne given to 2 of these patients
 24% (4) clinically declined and didn’t improve
 35% (6) declined but showed improvement clinically
 Oral prednisone used in addition to bronchodilators in 4 of 6
 No deaths
 1 patient with asthma history who died of sepsis found to have DIPNECH on autopsy
Treatment
 No formal evaluations of a treatment algorithm are available
 Resection of dominant lesion
 Oral/inh steroids w bronchodilators
 Chemotherapy
 Surgical lung resection
 Presence of lymph nodes has not been associated w worse outcome
 Lung transplantation (1pt, single lung, followed for 2 yrs)
 Observation
 ?Somatoastatin analogues
Somatostatin-receptor scintigraphy
(OctreoScan)
 Tumors often express somatostatin
 Labeled somatostatin analog (octreotide)
 Previously thought to be gold standard for diagnosis
 Sn approx 80-90%
 Somatostatin uptake may correspond to treatment response.
 Somatostatin targeted PET scan
 Sn as high as 100%, identified more lesions than SRS or CT
111In–DTPA–pentetreotide whole body scintigraphy (Octreoscan) showing an elective uptake
of the radiolabeled octreotide in the liver, expression of distant localization of the
neuroendocrine tumor of the lung (arrow).
Filosso P L et al. Eur J Cardiothorac Surg 2002;21:913-917
© 2002 Elsevier Science B.V.
Detail of the Octreoscan showing the liver metastase.
Filosso P L et al. Eur J Cardiothorac Surg 2002;21:913-917
© 2002 Elsevier Science B.V.
Patient’s octreotide scan
 No uptake in the lungs
 Increased uptake in the cecum
 Negative colonoscopy
Further investigation
 Predisposing factors?
 ? Hormonal component
 Tend to be middle-aged females
 Unclear if race/ethnicity plays a role
 Incidence?
 Treatment algorithm?
References
Ann Oncol (2001) 12 (9): 1295-1300.
 Davies SJ, Gosney JR, Hansell DM, et al. Diffuse idiopathic pul- monary neuroendocrine cell hyperplasia: an
under-recognised spec- trum of disease. Thorax. 2007;62:249-252.
 Cameron CM, Roberts F, Connell J, Sproule MW. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia:
an unusual cause of cyclical ectopic adrenocorticotrophic syndrome. Br J Radiol. 2011;84:e14-e17.
 25. Fessler MB, Cool CD, Miller YE, Schwarz MI, Brown KK. Idio- pathic diffuse hyperplasia of pulmonary
neuroendocrine cells in a patient with acromegaly. Respirology. 2004;9:274-277.
 26. Pinchot SN, Holen K, Sippel RS, Chen H. Carcinoid tumors. Oncologist. 2008;13:1255-1269.
Bronchopulmonary neuroendocrine tumors.Gustafsson BI, Kidd M, Chan A, Malfertheiner MV, Modlin IM
 Brambilla E, Travis WD, Colby TV, Corrin B, ShimosatoY. The new World Health Organization classification of lung
tumours. Eur Respir J. 2001;18:1059-1068.
 Aubry MC, Thomas CF Jr, Jett JR, Swensen SJ, Myers JL. Signifi- cance of multiple carcinoid tumors and tumorlets
in surgical lung specimens: analysis of 28 patients. Chest. 2007;131:1635-1643.
 Miller RR, Muller NL. Neuroendocrine cell hyperplasia and obliter- ative bronchiolitis in patients with peripheral
carcinoid tumors. Am J Surg Pathol. 1995;18:653-658.
 Sheerin N, Harrison NK, Sheppard MN, Hansell DM,Yacoub M, Clark TJ. Obliterative bronchiolitis caused by
multiple tumourlets and microcarcinoids successfully treated by single lung transplanta- tion. Thorax.
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 Aguayo SM, Miller YE, Waldron JA Jr, et al. Brief report: idiopathic diffuse hyperplasia of pulmonary
neuroendocrine cells and airways disease. N Engl J Med 1992;327:1285–8.
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