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Hepatoblastoma (HB) is a rare tumor and is the most common liver tumor in childhood [1]. 90% mainly occurred under 5 years of age, 70% occurred within 2 years of age, 4% occurred in newborns, with more insidious tumor onset, most of the early asymptomatic, and some have distant metastasis at the time of treatment.

Extramedullary Hematopoiesis (EMH) refers to hematopoietic activity that occurs in tissues other than normal bone marrow. This phenomenon usually occurs when bone marrow hematopoiesis is impaired or insufficient, such as myelofibrosis, myelodysplastic syndromes, certain types of anemia, or other bone marrow disorders. Extramedullary hematopoiesis can occur in multiple parts of the body, including the spleen, liver, lymph nodes, and other organs.

In normal circumstances, the bone marrow is the main site of hematopoiesis, but when the bone marrow is affected by the disease, the body may look for alternative hematopoietic sites in other places to maintain the generation of blood cells. Extramedullary hematopoiesis can be physiological, as during fetal development, or pathological and often associated with certain diseases.

The child, male, May, was treated in Dongguan Children's Hospital on January 24,2024 for "vomiting in April".

Current medical history

The child had vomiting without obvious inducement before April, which was obvious after eating during the day, with less vomit, which was the gastric content, and no vomiting after eating at night. I have been to many hospitals for treatment and given symptomatic treatment. The effect was not good.

Now, I came to the outpatient clinic of our hospital and did color ultrasound: Small bowel intussusception. The proposed "intussusception" is admitted for further diagnosis and treatment.

Past history

The child was healthy, denied history of bronchial pneumonia, febrile convulsion, seizure, thalassemia, history of hepatitis, history of surgery, trauma, blood transfusion, history of drug and food allergy.

Personal history, family history

The third child, the third birth, no asphyxia, no labor injury. Denied the recent history of living in the epidemic area and epidemic site, no history of exposure to radiation and poisons, and vaccination was carried out on time. Family history is not special.

Physical examination after admission

The abdominal shape was symmetrical, with no bulge and depression, no venous expansion of the abdominal wall, weakened abdominal respiration, and no bowel shape and peristaltic wave. The abdomen was soft, periumbilical tenderness (+/-), no obvious rebound pain, no rib under the liver and spleen, the whole abdomen, hepatic jugular vein reflux signs negative, liver area friction untouched, the gallbladder not touched, no tender, negative Murphy sign, both kidneys not touched, no tenderness and percussion pain. The bowel sounds were active, 6 times/min.

After admission

After admission, improve the relevant laboratory examination and imaging examination, among them, S6 hypoechoic group in the liver, consider liver focal nodular hyperplasia; CT dominal CT: Hepatic S6 mass, Focal nodular hyperplasia is more likely; serum alphafetoprotein 275.6 μg/L; on ultrasound-guided liver puncture on 29 January 2024, The pathological report was a liver malignancy, consider for hepatoblastoma; after completing the preoperative preparation, on 2024-2-03, S6 partial liver resection was performed under general anesthesia.

Image data

The outer edge of the liver was photointegrated, and the morphology, size and proportion of each lobe were normal, with a slightly low density mass in liver S6, about 20 mm 19 mm, and in the inner liver S8, about 6 mm 5 mm, portal and delayed density, no intrahepatic bile duct expansion, clear hilar structure, and no abnormal density. Imaging was shown in Figure 1.

 

Figure 1: Yellow arrow indicates the low-density mass shadow of liver S6 under the capsule of the liver with clear border (A-B); red arrow indicates the arterial stage (C).

Gross observation

Part of the liver tissue 4.5 cm × 3.2 cm × 2.4 cm, see a 3 cm × 2.2 cm × 2.1 cm large gray yellow nodule under the capsule, soft.

Microscopic performance

Under low magnification, the tumor is multinodular, infiltrative growth, composed of immature liver cells, the cytoplasm is eosinophilic or transparent, in the form of "light and dark"; under high magnification, the nucleoli are less than 2; tumor without capsule, sinus vessels covered with endothelial cells and extramedullary hematopoiesis see Figure 2.

 

Figure 2: A shows the general picture of the tumor; B shows the density of glycogen and lipids in the tumor with different light and dark areas (HE × 200); C shows the upper left corner of the normal liver tissue, and the lower right corner of the tumor (HE × 200); D shows dark cells lacking glycogen (HE × 400); E shows clear cells rich in glycogen (HE × 200); E shows the destruction of the network fibrous structure in the tumor (HE × 200).

Immuno-histochemical phenotype results

Tumor cells showed a diffuse positive expression of CK 8/18, Positive expression of Alpha Fetoprotein (AFP) tumor cells, β-catenin mixed positive expression of tumor cells, nucleus, cytoplasm and cytoplasm, positive expression of INI-1 (integrase interaction factor), positive expression of endothelial cells of the interstitial CD 34 sinusoidal vessels, positive expression in CK 7 tumors, Some positive expression of CD 10 tumors, TdT (terminal deoxynucleotidyltransferase) and CD 71 (extramedullary hematopoietic receptor), Hep par1 positive expression, phosphatidylinositide proteoglycan 3 (Glypican3) showed positive expression (Figure 3).

 

Figure 3: A shows CK 8/18, positive expression of tumor cells (IHC 400); B shows partial positive expression of AFP tumor cells (IHC 400); C shows positive expression of β-catenin tumor cells nucleus, membrane and plasma (IHC 400); D showed positive expression of INI-1 tumor cells (IHC 400); E positive expression of TdT extramedullary hematopoietic tissue (IHC 400); F positive expression of CD 71 extramedullary hematopoietic tissue (IHC 400); G positive endothelial cells (IHC 200); H positive expression of CK 7 tumors (IHC 200).

Pathological diagnosis and staging

(Liver) complete epithelial hepatoblastoma, mixed embryonic fetal type; COG Evans stage system stage Ib; clinical risk group low-risk group.

Follow-up and prognosis

According to the diagnosis and treatment of pediatric hepatoblastoma (2019 edition), children on February 21,2024, March 13, respectively, April 2 and April 23, four C5V regimen chemotherapy, "cisplatin, fluorouracil, vincristine" chemotherapy treatment, no fever, no gastrointestinal reaction, no bladder adverse reactions such as bleeding and mucosal damage. Repeat liver MRI on April 2,2024 showed no tumor recurrence, and serum alpha-fetoprotein decreased to 13.85 μg/L.

Difficulties in diagnosis and pathological analysis preoperative crude needle puncture tissue is limited, Immuno-histochemical β catenin tumor cell membrane and cytoplasm positive expression, no nuclear expression was observed, no definitive extramedullary hematopoietic tissue was seen, Hepatoblastoma and hepatocellular carcinoma were positive for all the tumor cells, including AFP, CD 10, Glypican3, and CK 8/18, All showed sinusoidal vessels, The more difficult identification between the two is made, The "light and dark" structure is faintly seen in the puncture tissue, And in this case, the child is 5 months old, Neither the child himself nor their mother had a history of hepatitis, Hepatocellular carcinoma mostly occurs in older children, And the tumor cell proliferation index is as high as 45%. If the proliferation index of highly differentiated hepatocellular carcinoma is slightly higher than that of normal liver. Greater than 4% and less than 10%. Comprehensive clinical history, imaging, morphology, and immunohistochemistry, the cture histopathology was considered as hepatoblastoma.

Surgical specimen tissue, besides the morphology seen in the puncture tissue, shows extramedullary hematopoietic tissue by immunohistochemical markers TdT and CD 71, and extramedullary hematopoiesis is rare in hepatoblastoma. It seems unlikely that hepatoblastoma cells themselves undergo a transition to HSC cloning [2], Because diffuse positive CK8/18 expression in tumor cells was marked by epithelial cell differentiation. It is conceivable that hematopoietic stem cells migrate from the yolk sac to the liver in early fetal life [3]. Can be preserved in the appropriate environment of the transformed fetal liver tissue, and this point may be the case where hepatoblastoma occurs in the abdominal cavity [4]. Extramedullary hematopoiesis occurs mainly in hematological tumors, but can also occur in patients with breast, lung, kidney, colon, gastric, pancreatic, or prostate cancer [5].

Puncture tissue β-catenin cell membrane and cytoplasm, surgical specimens mixed cell membrane, cytoplasm, and nucleus, β-catenin in normal fetal cells and immature cells in the nucleus.

Differential diagnosis analysis

Hepatocellular carcinoma: Liver plate thickening, generally more than 2 layers, different cell morphology, there is no light and dark structure, extramedullary hematopoiesis; most of the patients with hepatocellular carcinoma are older children, and children or mothers of children have a history of hepatitis B virus infection, and cirrhosis can be seen on imaging examination.

Mixed epithelial mesolobar hepatoblastoma: Composed of epithelial and mixed neoplastic mesostilobar components, most tumors contain mature and immature fibrous tissue, bone or bone like tissue.

Focal nodular hyperplasia: Stellate scar with radial fibers separated in the center of the lesion [6], There are often thick-walled blood vessels in the fiber septum, and the hepatocyte morphology of nodular hyperplasia is no different from that of normal hepatocytes, the gross tissue texture is tough, and the network fiber structure is complete.

Liver teratoma: Two or more germ tissues can be seen, showing differentiation into different germ layers.

Hepatocellular adenoma: Common in women aged between 20 and 40, related to the use of oral contraceptives, male hormone therapy and glycogen hoarding. It consists of transparent and differentiated hepatocytes with consistent size and morphology, no nuclear division, no duct area and central vein in the tumor.

Analysis of treatment and prognosis

At present, the multidisciplinary diagnosis and treatment with surgery and combined chemotherapy has become the standard model of hepatoblastoma treatment [7]. In this case, COG Evans stage Ib; the clinical risk group belongs to the low-risk group. For the timing of hepatoblastoma surgery, the protocol varied between different collaborative groups. The Pediatric Oncology Collaborative Group (COG) patients with stage PRETEXTI and stage may undergo primary resection without preoperative chemotherapy [8,9].

The comprehensive treatment of low-risk group hepatoblastoma with complete surgical resection and chemotherapy can achieve better long-term prognosis. The source of hematopoietic cells in hepatoblastoma is not clear, although only a small part of the tumor, but is of great significance to the diagnosis and classification of hepatoblastoma, pathological EMH by hematopoietic dysfunction, hematopoietic insufficiency and other pathological stress conditions (e. g., infection, advanced tumor, anemia and metabolic stress) trigger.

The authors declare that no financial support was received for the research, authorship, and/or publication of this article.

The authors gratefully acknowledge their colleagues in the department of pediatric general surgery and imaging for their support in data collecting.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author.

The studies involving humans were approved by the Ethics Committee of Dongguan Eighth People’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.

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