Hematoidin crystals in sputum smears: Cytopathology and clinical associations

Abstract

BACKGROUND: There has been limited correlation of hematoidin crystals (HC) in sputum with clinical and diagnostic characteristics, partly because they are difficult to recognize. The aim of this study was, therefore, to assess these relationships in a consecutive cohort of sputum samples from patients submitted to a cytology laboratory. METHODS: Adequate sputum samples from 489 individuals were enrolled in this study. These were fixed in ethanol, stained by the Papanicolaou method and examined microscopically. The normality of the distribution of the continuous variable (age in years) was examined using the Shapiro–Wilk normality test. As the data were not normally distributed, Kendall rank correlation was used to correlate age with the presence of HC. The Pearson's Chi-square test was used to determine if the proportion of cases with the presence of HC was different among the categorical data variables. A univariate binary logistic regression was used to determine the variables most strongly associated with HC presence. The results include odds ratios, 95% confidence intervals, Wald χ 2 statistics, and corresponding P values, with statistical significance assumed at P ≤ 0.05. Analyses were performed using IBM SPSS Statistics 22. RESULTS: The presence of HC in sputum was associated with increasing age ( P < 0.01), current smoking ( P < 0.001), chronic occupational exposure to dust ( P = 0.001), and hemoptysis ( P < 0.001). These crystals were most prevalent in patients with a diagnosis of carcinoma (93.9%), bronchiectasis (48%), silicosis (16.0%), and chronic obstructive pulmonary disease (0.8%). Crystals were not found in patients with acute bronchitis, asthma, or lung infections, including viral and bacterial pneumonia. CONCLUSIONS: There are clear associations linked to the finding of HC in sputum that may be helpful in pointing to a specific diagnosis, such as the possibility of underlying carcinoma.

Bone marrow hematoidin crystals in a pediatric patient with chondroblastic osteosarcoma

“…10 Studies have also found that chronic bleeding is associated with the presence of HCs as a recognized pathological feature in some disease entities, including lung cancer, silicosis, and bronchiectasis. 4,11 In the present case, chronic bleeding of the right femur over 14 days may have occurred, contributing to the formation of HCs.…”

“…7 Moreover, this unusual crystal may also occasionally be seen in pap smears 8 and sputum smears. 4 The origin of the HCs as a red cell breakdown product is well documented. Ultrastructurally, HCs consist of a core of tangled empty clefts suggestive of dissolved cholesterol crystals.…”

Pulmonary hematoidin deposition in a case of severe COVID19 pneumonia

“…The hematoidin deposits also vary in color from brightly yellow or golden to yellow-reddish colors. Hematoidin has been documented in a variety of conditions typically associated with chronic hemorrhage [6] , [7] , [8] , [10] , [14] . It has been reported in cytologic specimens of sputum and fine needle aspiration of necrotizing lung lesions; however, it is an unusual finding in cervicovaginal smears [6] , [15] .…”

“…Hematoidin has been documented in a variety of conditions typically associated with chronic hemorrhage [6] , [7] , [8] , [10] , [14] . It has been reported in cytologic specimens of sputum and fine needle aspiration of necrotizing lung lesions; however, it is an unusual finding in cervicovaginal smears [6] , [15] . Hematoidin was also reported in patients with traumatic and spontaneous cerebral hemorrhages [8] , acute gastrointestinal bleeding [7] , and in the skin [10] .…”

“…The DAD as well as in situ thrombi can be seen in association with a variety of infectious agents however the virus associated coagulopathy appears to be an essential part of the disease pathogenesis and in patients with severe COVID19 can histologically manifests as large vessel thrombi and/or fibrin microthrombi with resultant ischemic complications [1] , [4] , [5] . While hematoidin deposits have been documented in a wide range of neoplastic and non-neoplastic conditions [6] , [7] , [8] , [9] , [10] , [11] to the best of our knowledge it has not been reported in the setting of COVID19 pneumonia. Here we report a case of severe progressive COVID19 pneumonia that showed prominent deposition of hematoidin in the explanted lungs.…”