Missed diagnosis of lymphoma presenting with humoral hypercalcemia of malignancy due to cessation of oncological workup after negative computed tomography scans

2021 ◽  
Vol 14 (12) ◽  
pp. e246669
Author(s):  
Ellery Altshuler ◽  
Mahmoud Aryan ◽  
William King ◽  
Rolando Otero
Keyword(s):  
Ct Scan ◽  
Solid Tumours ◽  
Ct Scans ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Humoral Hypercalcemia ◽  
Hospitalised Patients ◽  
Computed Tomography Scans ◽  
Missed Diagnosis ◽  
Parathyroid Hormone Related Peptide ◽  
Head Neck

Malignancy is the most common cause of hypercalcemia among hospitalised patients and is frequently caused by elevations in parathyroid hormone-related peptide (PTHrP). The most common PTHrP-producing cancers are carcinomas of the head, neck and lung. Hypercalcemia can be the presenting sign of cancer and, in these cases, solid tumours are usually discovered on CT scan. In rare cases, lymphoma may also present with hypercalcemia. CT scan is less sensitive for lymphoma than for most solid tumours and the diagnosis may be missed. We present the case of a 69-year-old woman who presented with hypercalcemia in the setting of severe weight loss and elevated PTHrP. Oncological workup was stopped after unrevealing CT scans and an underlying lymphoma was missed. Our case emphasises the need for a comprehensive oncological workup for patients with unexplained hypercalcemia and elevated PTHrP, even when CT scans are unrevealing.

scholarly journals Is This Contrast? Is This Blood? An Agreement Study on Post-thrombectomy Computed Tomography Scans

2020 ◽  
Vol 11 ◽  
Author(s):  
Ronda Lun ◽  
Gregory B. Walker ◽  
Adrien Guenego ◽  
Mohammed Kassab ◽  
Eduardo Portela ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Ct Scan ◽  
Hemorrhagic Transformation ◽  
Ct Scans ◽  
Computed Tomography Scans ◽  
Kappa Value ◽  
Level Of Training ◽  
Global Agreement ◽  
Contrast Ct ◽  
Agreement Study

Background: Hemorrhagic transformation after acute ischemic stroke is a dreaded and severe complication of thrombolysis and thrombectomy. However, its detection on post-thrombectomy conventional non-contrast computed tomography (CT) scan can be complicated by the frequent (and sometimes concomitant) presence of contrast, resulting in changes in management.Aims: Our objective was to assess the inter- and intra-rater reliability for the detection of blood and/or contrast on day-1 post-thrombectomy CT scans.Methods: A total of 18 raters across 3 different specialties independently examined 30 post-thrombectomy CT scans selected from the Aspiration vs. STEnt-Retriever (ASTER) trial. They were asked to judge the presence of blood and contrast. Thirty days later, the same 18 raters again independently judged the 30 scans, in randomized order. Agreement was measured with Fleiss' and Cohen's K statistics.Results: Overall agreement on blood and/ or contrast presence was only fair, k = 0.291 (95% CI = 0.273–0.309). There were 0 scans with consensus among the 18 readers on the presence of blood and/or contrast. However, intra-rater global agreement across all 18 physicians was relatively high, with a median kappa value of 0.675. This intra-rater consistency was seen across all specialties, regardless of level of training.Conclusion: Physician judgment for the presence of blood and/or contrast on day-1 post-thrombectomy non-contrast CT scan shows limited inter-observer reliability. Advanced imaging modalities may then be warranted for challenging clinical cases.

scholarly journals Humoral Hypercalcemia of Malignancy with a Parathyroid Hormone-Related Peptide-Secreting Intrahepatic Cholangiocarcinoma Accompanied by a Gastric Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Katsushi Takeda ◽  
Ryosuke Kimura ◽  
Nobuhiro Nishigaki ◽  
Shinya Sato ◽  
Asami Okamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Parathyroid Hormone ◽  
Intrahepatic Cholangiocarcinoma ◽  
Immunohistochemical Staining ◽  
Elevated Serum ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Hypercalcemia Of Malignancy ◽  
Related Peptide ◽  
Humoral Hypercalcemia ◽  
Parathyroid Hormone Related Peptide

Humoral hypercalcemia of malignancy (HHM) is caused by the oversecretion of parathyroid hormone-related peptide (PTHrP) from malignant tumors. Although any tumor may cause HHM, that induced by intrahepatic cholangiocarcinoma (ICC) or gastric cancer (GC) is rare. We report here a 74-year-old male who displayed HHM with both ICC and GC and showed an elevated serum PTHrP level. Treatment of the hypercalcemia with saline, furosemide, elcatonin, and zoledronic acid corrected his serum calcium level and improved symptoms. Because treatment of ICC should precede that of GC, we chose chemotherapy with cisplatin (CDDP) and gemcitabine (GEM). Chemotherapy reduced the size of the ICC and decreased the serum PTHrP level. One year after diagnosis, the patient was alive in the face of a poor prognosis for an ICC that produced PTHrP. Immunohistochemical staining for PTHrP was positive for the ICC and negative for the GC, leading us to believe that the cause of the HHM was a PTHrP-secreting ICC. In conclusion, immunohistochemical staining for PTHrP may be useful in discovering the cause of HHM in the case of two cancers accompanied by an elevated serum PHTrP level. Chemotherapy with CDDP and GEM may be the most appropriate treatment for a PTHrP-secreting ICC.

Minimising medically unwarranted computed tomography scans

2012 ◽  
Vol 41 (3-4) ◽  
pp. 161-169 ◽  
Author(s):  
D.J. Brenner
Keyword(s):  
Computed Tomography ◽  
Ct Scan ◽  
Decision Rules ◽  
Clinical Decision ◽  
Ct Scans ◽  
Slowing Down ◽  
Powerful Approach ◽  
Computed Tomography Scans ◽  
Risk Balance ◽  
Major Factors

As computed tomography (CT) is such a superb diagnostic tool and individual CT risks are small, whenever a CT scan is clinically warranted, the CT benefit/risk balance is by far in the patient's favour. However, if a CT scan is not clinically warranted, this balance shifts dramatically. It is likely that at least 25% of CT scans fall into this latter category, in that they could either be replaced with alternative imaging modalities or could be avoided entirely. Use of clinical decision rules for CT usage represents a powerful approach for slowing down the increase in CT usage, because they have the potential to overcome some of the major factors that result in some CT scans being undertaken when they may not be clinically helpful.

Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy

2006 ◽  
Vol 290 (5) ◽  
pp. E761-E770 ◽  
Author(s):  
Naibedya Chattopadhyay
Keyword(s):  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Extracellular Calcium ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Calcium Sensing Receptor ◽  
Humoral Hypercalcemia ◽  
Cellular Events ◽  
Calcium Sensing ◽  
Parathyroid Hormone Related Peptide

The extracellular calcium-sensing receptor (CaR) plays a key role in the defense against hypercalcemia by “sensing” extracellular calcium (Ca2+o) levels in the parathyroid and kidney, the key organs maintaining systemic calcium homeostasis. However, CaR function can be aberrant in certain pathophysiological states, e.g., in some types of cancers known to produce humoral hypercalcemia of malignancy (HHM) in humans and animal models in which high Ca2+o, via the CaR, produces a homeostatically inappropriate stimulation of parathyroid hormone-related peptide (PTHrP) secretion from these tumors. Increased levels of PTHrP set a cycle in motion whereby elevated systemic levels of Ca2+o resulting from its increased bone-resorptive and positive renal calcium-reabsorbing effects give rise to hypercalcemia, which in turn begets worsening hypercalcemia by stimulating further release of PTHrP by the cancer cells. I review the relationship between CaR activation and PTHrP release in normal and tumor cells giving rise to HHM and/or malignant osteolysis and the actions of the receptor on key cellular events such as proliferation, angiogenesis, and apoptosis of cancer cells that will favor tumor growth and osseous metastasis. I also illustrate diverse signaling mechanisms underlying CaR-stimulated PTHrP secretion and other cellular events in tumor cells. Finally, I raise several necessary questions to demonstrate the roles of the receptor in promoting tumors and metastases that will enable consideration of the CaR as a potential antagonizing/neutralizing target for the treatment of HHM.

Histopathological Study on the PTHrP-Induced Incisor Lesions in Rats

2003 ◽  
Vol 31 (5) ◽  
pp. 480-485 ◽  
Author(s):  
Atsuhiko Kato ◽  
Masami Suzuki ◽  
Yayoi Karasawa ◽  
Tetsuro Sugimoto ◽  
Kunio Doi
Keyword(s):  
Parathyroid Hormone ◽  
Rat Model ◽  
Causative Factor ◽  
Histopathological Study ◽  
Middle Region ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Cell Height ◽  
Humoral Hypercalcemia ◽  
Parathyroid Hormone Related Peptide ◽  
Calcification Process

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected. Incisor fractures were observed grossly. Microscopically, hypercalcified dentin, dentin niche with osteodentin, and thinning of dentin were observed. Hypercalcified dentin was observed as a basophilic line of calcified dentin without associated odontoblastic changes, whereas dentin niche and thinning of dentin occurred with osteodentin and loss of cell height, respectively. In contrast with hypercalcified dentin, which was distributed throughout the dentin, dentin niche and thinning of dentin were localized to the labial area of the apical and middle region, and to the labial and lingual areas of the middle and incisal region, respectively. These results suggest that hypercalcemia affected the entire calcification process resulting in hypercalcified dentin, and that high PTHrP concentrations affected selective populations of odontoblasts resulting in formation of dentin niche and thinning of dentin. The localization of dentin niche and thinning of dentin also suggest that PTHrP may also be involved odontoblastic development in the rat.

Immunoreactivity of plasma parathyrin-related peptide: three region-specific radioimmunoassays and a two-site immunoradiometric assay compared

1991 ◽  
Vol 37 (10) ◽  
pp. 1781-1787 ◽  
Author(s):  
W A Ratcliffe ◽  
S Norbury ◽  
R A Stott ◽  
D A Heath ◽  
J G Ratcliffe
Keyword(s):  
Monoclonal Antibody ◽  
Plasma Concentrations ◽  
Diagnostic Utility ◽  
Immunoradiometric Assay ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Related Peptide ◽  
Control Subjects ◽  
Humoral Hypercalcemia ◽  
The Mean ◽  
Parathyroid Hormone Related Peptide

Abstract We measured parathyrin (parathyroid hormone)-related peptide (PTHRP) in plasma by three region-specific RIAs and compared them with an established two-site immunoradiometric assay (IRMA) of PTHRP1-86 in samples from control subjects and from patients with primary hyperparathyroidism (PH) and humoral hypercalcemia of malignancy (HHM). The two direct RIAs of PTHRP1-34 and PTHRP37-67 were specific for regions 9-18 and 52-61, respectively. In the extraction RIA of PTHRP1-34 we used an affinity gel containing a monoclonal antibody specific for the 17-27 sequence; cross-reacting PTHRP species eluted from the gel were assayed by the RIA of PTHRP1-34. PTHRP1-86 plasma concentrations by IRMA were less than 0.23 pmol/L in control subjects and patients with PH, and were significantly increased in patients with HHM (mean 6.1 pmol/L, P less than 0.001). In contrast, plasma PTHRP1-34 concentrations were not significantly different in the three groups; in HHM patients, the mean was 190 pmol/L. Plasma PTHRP37-67 concentrations were similar in control and PH groups and, although significantly increased in HHM patients (mean 440 pmol/L, P less than 0.002), showed poor diagnostic discrimination. PTHRP1-34 concentrations after affinity extraction of plasma were also significantly higher in HHM patients (mean 10.7 pmol/L, P less than 0.001), but showed incomplete diagnostic discrimination. We conclude that the diagnostic utility of the direct RIAs for quantifying PTHRP is markedly inferior to the IRMA of PTHRP1-86.

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