The fifth edition of the World Health Organization (WHO) T-cell-dominant tumor-like lesions has recently added indolent T-lymphoblastic proliferation (iT-LBP) [1]. iT-LBP is a newly discovered non-neoplastic disorder characterized by hyperplasia of extrathymic T-lymphoblastic cells and expressing a thymic cortical phenotype. In recent years, reports of iT-LBP have markedly increased. We report a case of iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma and review of related literature.

Indolent T-lymphoblastic proliferation is a very rare disorder and is characterized by the proliferation of extrathymic T lymphoblasts. In recent years, there has been a relative increase in cases of iT-LBP, perhaps based on our growing understanding of the disease. Isolated iT-LBP has been observed [2], but most of the iT-LBP cases have been seen in conjunction with other disorders, including Castleman disease, hepatocellular carcinoma, follicular dendritic cell tumors, angioimmunoblastic T-cell lymphoma, myasthenia gravis, and acinic cell carcinoma [3–8]. Our patient was diagnosed with iT-LBP with fibrolamellar hepatocellular carcinoma, a special subtype of rare hepatocellular carcinoma that often occurs in young individuals without viral hepatitis or other signs of cirrhosis [9]. AFP levels can be normal or mildly elevated in fibrolamellar carcinoma [10]. Studies have shown that 80% of fibrolamellar carcinoma develops before the age of 35, while only 11% of fibrolamellar carcinoma develops after the age of 40 [11]. This case involved a middle-aged patient with negative AFP expression. Gross tissue analysis showed cicatricial fibrosis at the center of the tumor [12], which is similar to focal nodular hyperplasia. Microscopically, the fibrous tissue in the tumor was arranged in parallel to separate the nest of tumor cells, and the neoplastic hepatocytes have abundant eosinophilic cytoplasm, which may be caused by an increase in the number of mitochondria [13]. The results of immunohistochemical analysis did not support liver metastases from colorectal adenocarcinoma, and thus is described as a primary liver tumor.

We also need to identify hepatocellular adenoma in non-cirrhotic liver tumors, hepatocellular adenoma cut section is soft and uniform, although necrosis, heamorhage, or fibrosis are frequent. The margins of the lesion are ambiguous, grossly and microscopically with little or no fibrous capsule. Microscopically, hepatocellular adenoma is composed of benign hepatocytes arranged in regular plates, usually one or most two cell thick. Tumour hepatocytes have normal cytoplasm, clear cytoplasm, Steatotic cell, or contain pigment. Nuclear and mitoses are rare. Hepatocellular adenoma parenchyma has isolated arteries without bile ducts or multifocal lymphocyte infiltration. TdT-positive lymphocytes are absent in normal liver. The nature of the TdT-positive T lymphocytes infiltrating the tumor in this case is unclear. Given the rarity of this co-occurrence, further studies are needed to determine whether there is a correlation.

There is currently a need to differentiate iT-LBP from T-lymphoblastic lymphoma/leukemia. In this case, the immunophenotype of multifocal clusters of proliferating lymphocytes showed T lymphocytes, and IHC was unable to distinguish T lymphoblastic lymphoma/leukemia. Because the iT-LBP immunophenotype overlaps with T lymphoblastic lymphoma/leukemia expression, and both have high Ki-67 proliferation index expression, we were prompted to consider that this case is T-lymphoblastic lymphoma/leukemia with fibrolamellar hepatocellular carcinoma. However, comparing the two morphologies, T-lymphoblastic lymphoma/leukemia is an aggressive tumor composed of medium-sized blast cells that progress very rapidly when left untreated. In contrast, iT-LBP lymphocytes were small, with little cytoplasm, round basophilic nuclei, fine chromatin, indistinct nucleoli, infrequent mitoses, no cellular atypia, and an indolent clinical course. The patient underwent bone marrow biopsy, with no lymphoma cell infiltration found. The course of disease and the diagnostic criteria proposed by Ohgami et al. [14] can also help us in its diagnosis by distinguishing it from T lymphoblastic lymphoma. In this case, there are many small B lymphocytes surrounding T cells, and lymphoid follicle formation was observed. Reactive hyperplasia and small B cell-derived lymphoma should also be distinguished in differential diagnosis.

All the molecular studies on iT-LBP reported in the literature have confirmed that there is no clonal T-cell receptor (TCR) gene rearrangement [2–7]. Polymerase chain reaction analysis of this patient showed no monoclonal T-cell proliferation. Therefore, T lymphoblastic lymphoma/leukemia was excluded.

To date, Wang [5] and Shin Eun [13] have reported that iT-LBP combined with hepatocellular carcinoma may be sources of immature T cells. Wang suggested that HCC may recruit immature T lymphocytes from the thymic cortex or bone marrow into the tumor by some unknown mechanism. Shin Eun suggested that certain cytokines produced by HCC-transformed hepatocytes may stimulate the proliferation of immature T cells. This clinical feature of our patient may also be due to the abovementioned reasons, although further studies using a larger sample size are necessary to determine the nature and pathogenesis of these immature T cells.

Nine months have passed since surgical resection, but the patient remains well and has shown no tumor recurrence, with CT scans revealing no development of lymphoblastic lymphoma, and peripheral blood tests show no sign of leukemia.

Indolent T-lymphoblastic proliferation combined with hepatocellular carcinoma has been reported in the literature to have a poor prognosis [5, 14]. The prognosis of this case is better than that reported by Wang and Shin Eun, which may be due to the iT-LBP combined with a special type of fibrolamellar hepatocellular carcinoma. However, recent reports suggest that the combination of iT-LPB with hepatocellular carcinoma has nothing to do with the specific type of liver cells [15]. This case is indeed a special type of hepatocellular carcinoma with novel symptoms, further expanding the clinical spectrum of the disease. In conclusion, both iT-LBP and fibrolamellar hepatocellular carcinoma are rare, and their exact pathogenesis and clinicopathological significance have yet to be further elucidated.