木瓜直播

A 30-year-old Indian man presents to a hospital clinic in Doha, Qatar, with severe pain and numbness in his entire lower jaw, noting that the symptoms developed 4 days earlier. Although his medical history is unremarkable, the patient explains that for the past month, due to unknown reasons, he has lost 4 kg. During that time, he has also been intermittently feverish, and generally has felt ill.

Clinicians assessing him note that he appears pale, has obvious submandibular swelling on both sides of his mouth, and can open his mouth only slightly due to pain. His history reveals that he has suffered no trauma or had recent skin or mucosal eruptions; he has not had a hep­atitis vaccination.

Neurological assessment finds the patient has reduced sensitivity to pain, touch, and temperature changes over the mental area, but normal vibration sensa­tion and motor function. The rest of his ner­vous system as well as other systems are intact.

Laboratory Results

Lab tests identify the following:

• Low hemoglobin of 3.6 mg/dL (nor­mal range: 13.0–17.0 mg/dL)

• Platelet count of 12×10³ μL (normal range: 150–400×10³/μL)

• White blood cell count of 6.3×10³/μL (normal range: 4.0–10×10³/μL)

Clinicians rule out infectious causes including Epstein Barr virus and HIV; serological tests for herpes, however, were not ordered. Test results for antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, and rheumatoid fac­tor are all negative.

Based on signs of bicytopenia, clinicians take a periph­eral smear. Analysis shows marked neutropenia with left shift, dysplastic features, and 47% circulating blasts with some Auer rods -- a picture highly suggestive of acute myeloid leukemia (AML). That is confirmed by flow cytometry of bone marrow aspirate, which shows 52% abnormal pre­cursors. Chromosome analysis reveals 45, X,-Y with t(8;21) (q22;q22); RUNX1-RUNX1T1.

To further investigate the reason for the patient's neurological def­icit, clinicians order magnetic resonance imaging of the head. This reveals subtle heterogeneous marrow signal of the bone marrow with no focal destructive bony lesions or soft tissue masses, with a possibility of underlying infiltrative pro­cess.

In addition, almost complete opacification of the left mas­toid air cells suggests possible left mastoiditis, but there is no other def­inite abnormality of the focal brain parenchyma; all ventricles appear normal, and there is no evidence of a midline shift or deformity. The sub­mandibular glands are also normal, and no destructive bony lesion is detected.

The patient is started on induction therapy with cytarabine and an anthracycline using the standard 7+3 protocol (7 days cytarabine + 3 days an­thracycline). (The standard combination is the 7+3, with a 7-day continuous infusion of cytarabine at the dosage of 100 or 200 mg/m² per day on days 1 to 7 and daunorubicin at 60 mg/m² per day on days 1 to 3.)

Following the first induction cycle, the patient's jaw pain and swelling are relieved. Treatment also resolves the decreased sensation and pares­thesia affecting the left half of the mental area, although these symptoms persist over the right half of the area even following the second induction cycle. At 7 weeks post-diagnosis, an x-ray of the skull shows the heterogeneous texture of the mandible.

In accordance with hospital protocol, the patient receives a total of two cycles of induction and three cycles of consolidation; examination of bone marrow upon completion of treatment reveals 4% blasts. The patient is discharged to return to his home country.

Discussion

Clinicians presenting this of numb chin syndrome (NCS) note that it is a rare and under-diagnosed neu­ropathy, and that it is even more unusual to encounter NCS as a presenting feature of AML. The authors explain that they report this patient's case to encourage clinicians to consider AML as an important differential in patients presenting with NCS where there is no preceding trauma or infection.

NCS, also known as mental nerve neuropathy, affects the inferior alveolar branch of the trigeminal nerve and is generally marked by a lower lip and chin hypoes­thesia, paresthesia, and in rare cases, pain.

NCS has very diverse causes. are caused by odontogenic diseases such as trauma, dental extraction, dentoalveolar abscess, and osteomyelitis. Other non-malignant causes include non-odontogenic infections (bacterial, viral, Lyme disease, syphilis, and HIV), multiple sclerosis, benign sensory trigeminal neuropathy, radiotherapy, chemical exposure, vasculitis, systemic amyloidosis, sickle cell disease, sarcoidosis, diabetes mellitus, and vertebrobasilar insufficiency.

As this case illustrates, NCS is also associated with the presentation, progression, or relapse of malignancy, and is thought to be associated with presentation of both solid tumors and hemato­logic malignancies in an estimated 30-50% of patients, although this has yet to be confirmed by large, prospective studies.

Any lesion along the course of the trigeminal nerve, from its nucleolus in the pons down to the mandibular endings, can re­sult in NCS. Malignancy-associated NCS may result from direct infiltration of the bone or nerve, leptomeningeal seeding, or inflammation or compres­sion of the nerve.

The case authors urge physicians who see a patient with NCS to be vigilant for potential cancer, since NCS can be an initial sign of an undiagnosed malignancy; the syndrome may also signal cancer recurrence. NCS has been found in metastatic malignancies of the liver, lung, kidney, breast, and prostate, among others.

As such, the authors urge clinicians assessing patients with these symptoms to take a detailed history that includ­es previous history of malignancies and risk factors, and to perform a physical examination of the aforementioned solid organs followed by appropriate imaging.

Reports of NCS as a presenting symptom of a hematological malignancy are relatively rare; NCS has been linked most often with non-Hodgkin lymphoma and acute lymphoblastic leukemia. This is believed to be only the sixth reported case of NCS associated with AML, the authors note.

An interesting aspect of the case, they say, is the patient's chromosomal abnormal­ities -- t(8,21), which carries a favorable prognosis. Another such reported case involved a 33-year-old woman who presented with chills, malaise, nausea and vomiting, and numbness of the lower lip and chin. She had a normal computed tomogra­phy scan of the brain and leukocytosis with circulating blast forms -- morphologically this was consistent with the French-American-British M2 subtype. After 12 days of induction chemotherapy with cytarabine and daunoru­bicin (7+3), her numbness was completely resolved, whereas in the current case, the paresthesia persisted after the pain had resolved.

Approach to Chemotherapy

While the case authors do not describe their patient's treatment protocol in detail, they noted that the standard combination therapy for AML is the 7+3 approach, with a 7-day continuous infusion of cytarabine at 100 or 200 mg/m² per day on days 1 to 7 and daunorubicin at 60 mg/m² per day on days 1 to 3.

Recent data suggest that the 45 mg/m² daily dose of daunorubicin may be suboptimal in patients younger than 65, although it has not been established that the 90 mg/m² daily dose should be preferred over the 60 mg/m² daily dose endorsed by the 2017 European LeukemiaNet expert panel .

The authors also compiled a summary of the previous cases, showing that they were all de novo AML. In their patient's case, it could not be determined whether the symptom was related to infiltration of the mental nerve itself by leukemic cells or to entrapment caused by marrow infiltration at the mandible area. The patient's severe thrombocytopenia at presentation suggested a high risk of bleeding, and combined with the risk of damaging the nerve further, the decision was made not to biopsy the mandible; the exact pathophysiology of her numb chin, therefore, could not be determined.

Conclusion

The case authors conclude that AML -- "one of the most sinister diagnoses" -- should be considered in a patient presenting with NCS and that further research is needed to study the association between NCS and the prognostic potential of specific cytogenetic abnor­malities in this malignancy.

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