Material and Method: A retrospective study of 2 years duration was conducted to identify the morphological spectrum of diseases presenting with hemoptysis. A total of 243 lung biopsies obtained by various methods were retrieved in this study period and 20 cases with hemoptysis of undetermined etiology were detected.
Results: Based on imaging and histopathology findings, the etiological causes of hemoptysis were divided into hemoptysis with and without capillaritis or due to tumor/tumor-like lesions and due to miscellaneous conditions. The most common etiology was vasculitis followed by infections.
Conclusion: Histopathology helps to detect the etiology, particularly in cases of hemoptysis due to non-immunologic causes. In immunologic cases, histopathological findings may support the diagnosis in correlation with the clinical/imaging features.
The common causes of hemoptysis include pulmonary tuberculosis (TB), malignancy, bronchiectasis, chronic bronchitis, pneumonia, and fungal infections. The other rare causes are vasculitis due to collagen vascular diseases and hereditary hemorrhagic telangiectasia, essential cryoglobulinemia, Behcets disease, acute lung transplantation rejection, drug-induced (e.g., chemotherapeutic agents, propylthiouracil), idiopathic pulmonary hemosiderosis, and toxin or inhalation injury [3].
About 30% of cases attending respiratory clinics and presenting with hemoptysis pose a problem in clinical diagnosis, and the histopathology plays a vital role in diagnosing these conditions. The condition can be localized or diffuse depending upon the underlying etiology [4]. Intra alveolar hemorrhage, fibrin deposition, and hemosiderinladen macrophages associated with or without capillaritis are the common findings observed in cases of diffuse alveolar hemorrhage (DAH) [5]. Radiologically, DAH shows patchy/ diffuse bilateral areas of lung consolidation mainly involving the lower lobes and perihilar regions [6].
A literature search revealed only a few reports on using histopathological interpretation in diagnosing unknown causes of hemoptysis. This is vital to diagnose and treat the condition earlier, as it prevents disease progression, and constituted the reason for conducting the current study. This study aims to identify the various uncommon aetiologies of hemoptysis based on histopathological features and the pathologists approach in diagnosing this condition.
Ethical approval for this study was obtained from PSG Institute of Medical Sciences & Research (Approval number: 20/117, Date: 27.05.2020).
Histopathological Findings
Based on imaging and histopathological findings, the
etiology of hemoptysis was divided into localized and
diffuse/bilateral pulmonary involvement (Table I).
Depending upon the histological findings, the causes of
hemoptysis were further divided into
Table I: Etiological classification based on imaging & histopathological findings.
- Hemoptysis with capillaritis (Table II)
Table II: Causes of hemoptysis with capillaritis.
- Hemoptysis without capillaritis (Table III)
Table III: Causes of hemoptysis without capillaritis.
- Unusual tumors and tumor-like lesions (Table IV)
Table IV: Unusual tumors and tumor-like lesions of the lung.
- Miscellaneous uncommon causes
Miscellaneous uncommon causes are listed below:
Pulmonary Alveolar Microlithiasis (n=1)
HRCT of a 34-year-old male who presented with
hemoptysis showed bilateral ground-glass densities with
septal calcification -? Interstitial lung disease. TBLB
sections showed distended alveoli containing concentric
lamellated, calcific material with few hemosiderin-laden
macrophages.
Pulmonary Endometriosis (n=1)
A 43-year-old man with a history of cirrhosis secondary
to hepatitis C had recurrent episodes of hemoptysis.
Bronchoscopy revealed a mucosal white patch in the left
lingular segment. The biopsied lesion showed lung tissue
intimately admixed with a focus of endometrial glands
and stroma. CD 10 immunostaining of the stroma, as
well as estrogen and progesterone receptor staining of
the glandular component, were both consistent with
endometriosis (Figure 1A-D).
Figure 4: Hemosiderin-laden macrophages A) (H&E; x40). B) (Perls stain; x40).
Pulmonary Intravascular Haemangioma (n=1)
HRCT of an elderly male showed multiple small nodules
in both the lungs and a lobulated enhancing soft tissue
lesion attached to the anterior wall of the right atrium-?
Malignancy. TBLB sections showed lung parenchyma
with medium to large-sized vessels containing an
intraluminal, adherent lesion of tubular vascular spaces
lined by endothelial cells. CD31 & CD34 immunostaining
highlighted the endothelial cells. Since the right atrial
mass could not be biopsied, the clinical/imaging findings
were correlated and the final HPE diagnosis made was
intravascular capillary haemangioma/?fragmented from
cardiac haemangioma.
Haemoptysis with Capillaritis (Granulomatosis with
Polyangiitis & Eosinophilic Granulomatosis with
Polyangiitis)
Pulmonary vasculitis is characterized by inflammation of
the small and medium-sized vessel wall, causing pulmonary
hemorrhage. Imaging studies show multiple lung cavitary
nodules/masses, which may mimic metastasis. Also in
some conditions, the lung infiltrates are transitory making
the diagnosis a challenging one [7].
Schnabel et al. stated that histopathological findings may vary depending upon the type of biopsy. They found out that the yield of guided lung biopsy is high when compared to TBLB since gross lesions are easily visible. Similarly, most of our cases had undergone guided biopsies and were adequate [8].
Travis et al. suggested that capillaritis is a morphologic marker of DAH in their study. They concluded that capillaritis and necrotizing granulomatous inflammation with mixed inflammatory cell infiltrate were pathognomonic features of GPA. Parenchymal necrosis, extravasated fibrin, and scattered multinucleate giant cells in a biopsy could suggest the diagnosis of a GPA even in the absence of granuloma. The destruction of the vessel wall can be highlighted by VVG elastic stains. However, correct sampling is essential for the maximum yield [9,10].
The diagnosis of EGPA can be made if the biopsy shows granulomatous vasculitis with extravasated eosinophils and evidence of eosinophilic pneumonia [11]. Correspondingly, three cases in our series showed capillaritis and the remaining two were diagnosed based on relevant clinical and imaging findings.
Haemoptysis without Capillaritis
Fungal Infection: Alveolar hemorrhage resulting from
fungal infection is infrequent. The possible pathogenesis
of hemoptysis in fungal infection could be 1) due to
chronic inflammation as the granulation tissue lining the
cavity is rich in capillaries, 2) these new vessels are rather
fragile and can rupture easily, and 3) erosion of the blood
vessels adjacent to the cavity [12]. The presence of calcium
oxalate crystals in a patient with a cavitary lesion will raise
suspicion of a fungal infection and the pathologist should
search for the same in the adjacent area [13]. Likewise, our
cases also had similar histology which would have led to
hemoptysis.
Silicosis: An autopsy case study by Kyeong et al. revealed that unlike silicosis which affects mainly the lung parenchyma, silico - tuberculosis also affects the pulmonary vasculature causing hemoptysis [14]. Our cases did not have evidence of tuberculosis. Streak-type hemoptysis seen in our cases could be explained by the destruction of small-sized blood vessels by fibrosis and chronic inflammation [15].
Unusual Tumors and Tumor-Like Lesions of the Lung
Primary Pulmonary Mesenchymal Tumors: Accounts for
less than 1% of all lung malignancy. These tumors show
lineage differentiation and can be diagnosed in the lung
with similar histological and immunological criteria as in
other sites (soft tissue) [16]. Pulmonary hamartoma is the
most common benign mesenchymal tumor of the lung, and
is predominantly seen in older males. Geramizadeh et al.
and Ahmed et al. in their study stated that the occurrence
of hemoptysis in hamartoma is very rare and results from
giant or endobronchial tumors causing erosion of the
vessels [17,18]. In contrast to their findings, our patient
was a middle-aged female with a small peripherally located
pulmonary hamartoma.
According to Hashimoto et al., it is important to identify and differentiate metastatic mesenchymal tumors correctly, since most mesenchymal tumors presented as occult/unknown primary with pulmonary metastatic foci [19]. Identically, one of our cases had metastatic LMS with a known diagnosis of primary LMS of the thigh.
Mucoepidermoid Carcinoma (MEC): MEC is a rare salivary gland type endobronchial tumor with mucous secreting cells, squamous cells, and intermediate cells. A definitive diagnosis requires bronchoscopy and representative biopsy as this tumor exhibits morphological heterogeneity. It can be misdiagnosed as primary nonsmall cell lung carcinoma if the biopsy is inadequate [20,21]. The diagnosis of this rare neoplasm was possible since ours was a pneumonectomy specimen.
Myelolipoma: Pulmonary myelolipoma is distinctly unusual and rarely presents with hemoptysis. Embolic origin, reticuloendothelial cell metaplasia, and proliferation of hematopoietic stem cells are possible mechanisms of histogenesis. Tumour arising adjacent to the bronchial cartilage may show bony trabeculae and this explains the possible histogenesis of the metaplastic theory [22]. Our case also revealed a similar histology.
Miscellaneous Uncommon Causes
Pulmonary Endometriosis: Pulmonary endometriosis
is a rare form of extra pelvic endometriosis, occasionally
reported in men. Cases of male endometriosis have
typically been linked to increased circulating estrogen
levels. Peripheral conversion of androstenedione and
testosterone to the circulating estrogens was noted in men
with cirrhosis of the liver [23]. Our patient had a history of
cirrhosis, possibly leading to an altered hormonal state that
interacted with a reactive/metaplastic process.
Pulmonary Alveolar Microlithiasis (PAM): PAM is a rare autosomal recessive lung disease characterized by the accumulation of concentrically laminated calcospherites within the alveolar spaces. Lauta in his study stated that there is a striking clinico-radiologic disparity in this condition [24]. Since our patient did not have other system involvement, the possibility of PAM over secondary calcification was favored by correlating the clinical and imaging features.
Pulmonary Intravascular Haemangioma: The coexistence of cardiac and pulmonary haemangioma is very rare and very few reports of such an association have been described so far. Imaging studies may help in diagnosing cardiac haemangioma while histopathology is essential for confirmation. Complete excision is the treatment of choice in resectable cardiac haemangioma and solitary pulmonary haemangioma [25]. Since the general condition of the patient was poor, resection was not possible in our case. Fragmented emboli from a cardiac haemangioma could also be considered as a differential.
In conclusion, in immunologic causes of hemoptysis, histopathological findings may support the diagnosis in correlation with the clinical/imaging features. However, in cases of non-immunologic causes of hemoptysis, a histopathologic examination is mandatory over clinical/ imaging studies. The cases presented here are incredibly rare diseases with an uncommon presentation. The diagnosis is often missed or delayed, due to a low index of suspicion. Histopathological examination is imperative in unexplained cases of hemoptysis as it plays a vital role in therapy decisions.
ACKNOWLEDGEMENT
The authors thank Dr. Anupama Moorthy (Prof & Head,
Dept. of Respiratory medicine) and Dr. Devanand (Prof
& Head, Dept. of Radiology) for their valuable discussions
and feedback.
CONFLICT of INTEREST
The authors declare no conflict of interest.
FUNDING
The authors declared that this study has received no
financial support.
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