Overall clinical course of indeterminate dendritic cell tumor patients without skin lesions: A rare case report

Abstract

BACKGROUND

Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed.

CASE SUMMARY

This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.

CONCLUSION

For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

Key Words: Indeterminate dendritic cell tumor, Clinical development, Surgical biopsy, Collective management, Dendritic cell, Case report

Core Tip: The clinical course in indeterminate dendritic cell tumor (IDCT) patients without skin lesions was about 2 years. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. No tumor cells or pathogens were found in the three subsequent ascites analyses. The correct diagnosis was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes. IDCT is fairly rare, and the surgery for biopsy is important for the IDCT. Therefore, the collective management of IDCT patients in a hospital specializing in rare diseases is interesting and cost-effective.

INTRODUCTION

Indeterminate dendritic cell tumors (IDCTs) originate from the stromal-derived dendritic cells, a special type of cell involved in the process of antitumor immunity. The incidence of IDCT is very low. Fewer than 1% of neoplasms originating from lymph tissues are diagnosed as IDCT[1]. A recent study[2] showed that only one patient was diagnosed with IDCT (0.4%, 1/274) among the histiocytic and dendritic neoplasm cases recorded from 1995 to 2018. Although the number of IDCT cases is rare, some commonalities and differences have been analyzed in the current literature.

Skin lesions are found in almost all IDCT patients. Most patients are diagnosed with IDCT by biopsy of the skin lesions[3] or mucosa lesions[4]. However, a series of special IDCT cases have been reported recently because of the rarity of patients without skin lesions. A study reported that a patient had spontaneous splenic rupture due to the excess proliferation of indeterminate dendritic tumor cells in the spleen[5]. Indeterminate dendritic tumor cells can arise in the pancreas[6]. When the IDCT invades the abdominal organs, the difficulty of early biopsy increases greatly, and consequently, the diagnosis and treatment of this type of IDCT patient are delayed.

Although crucial for developing optimal treatment plans and predicting patient prognosis, the overall clinical development of IDCT involving the abdominal organs has rarely been reported. Additionally, the diverse types of lesions identified via IDCT may lead to misdiagnosis, especially in the absence of typical skin lesions. However, IDCT, a type of immune cell-related cancer, is worthy of mention[7]. The specific antitumor immune effects of dendritic cells disappear in IDCT.

This study reports the overall clinical course of a patient diagnosed with IDCT although typical skin lesions were absent.

CASE PRESENTATION

Chief complaints

A 59-year-old woman was admitted to the Department of Digestive Diseases because of the main complaint of persistent abdominal distension

History of present illness

Three years prior, the patient had visited a urologist and was diagnosed with a ureteric calculus. Her liver, bile duct and mesenteric lymph nodes were in good condition at the time of the imaging examination. She was discharged from the hospital after receiving surgical treatments. Two years later, this patient presented with abdominal pain but not jaundice. Based on the lasting contrast-enhanced bile duct lesions on magnetic resonance imaging (MRI) (Figure 1A), cholangiocarcinoma was suspected in this patient. Importantly, enlarged mesenteric lymph nodes were found on MRI (Figure 1B). The patient refused surgical treatment for the bile duct lesions and asked to leave the hospital soon thereafter.

Figure 1 Abdomen magnetic resonance imaging and computed tomography findings of the female with indeterminate dendritic cell tumor. A: Lasting contrast-enhanced of lesions in the bile duct in the magnetic resonance imaging (MRI) at the first admission; B: Enlarged mesenteric lymph nodes in MRI at the first admission; C: Tumor-like lesions in the bile duct in the computed tomography (CT) examination at the second admission; D: Enlarged mesenteric lymph nodes in the CT examination at the second admission.

Six months later, this patient visited the hospital again because of mild abdominal distension. The tumor-like lesions located in the bile duct and liver were still present, but the mesenteric lymph nodes were enlarged on computed tomography (CT) (Figure 1C and D). After the patient refused to receive chemotherapy, she asked to leave the hospital after the alleviation of her abdominal distension. In the last three years, no rash on the skin or mucosa was observed in this patient.

History of past illness

The patient had no significant medical history and no tobacco or alcohol use.

Personal and family history

There was no history of hepatitis, other infectious diseases or recent trauma and no family history of rare diseases.

Physical examination

The patient’s body temperature was 36.9 °C, and her respiratory rate was 17 breaths/min. Her pulse rate was 83 beats/min, and her blood pressure was 101/69 mmHg. She was cooperative with the examination, reporting mild tenderness upon palpation of her upper abdomen. No enlarged lymph nodes were palpated, and no skin lesions were observed. The body mass index of this patient was 19.1 cm (150 cm in height and 43 kg in weight).

Laboratory examinations

The results of several abnormal blood examinations were recorded. The carbohydrate antigen 125 (CA-125) level was as high as 223.71 units/mL (reference range, 0–35). The level of gamma-glutamyl transferase (γ-GGT) was increased to 337 units per liter (reference range, 7–45), and the concentration of albumin was very low, at 22 g per liter (reference range, 40–55). Moreover, the patient’s hemoglobin level was decreased, at 90 g per liter (reference range, 110-150). No tumor cells were found in the three histological analyses of ascites. Both microbial examination for Mycobacterium tuberculosis and gene sequencing for M. tuberculosis DNA in the ascites were negative. Furthermore, the result of the bone marrow test for tumor cells was negative.

Imaging examinations

CT imaging revealed general dilatation of the intrahepatic bile ducts as well as many enlarged lymph nodes in the small bowel mesentery. The size of the largest lymph nodes was approximately 2 cm (Figure 2A and B). Compared to the previous imaging data, a fairly swollen omentum and mesentery, along with massive ascites, were observed in this CT examination (Figure 2C and D).

Figure 2 Increasingly enlarged mesentery lymph nodes and swollen omenta of the female with indeterminate dendritic cell tumor in the computed tomography examination. A: Ascites and enlarged mesentery lymph nodes; B: Swollen omenta and mesentery; C: Ascites in the perihepatic areas; D: Blurred abdominal gaps.

FINAL DIAGNOSIS

Consequently, cholangiocarcinoma or a rare malignant disease was first suspected. The worsened abdominal distension and massive ascites made the patient feel concerned. Finally, she underwent surgical treatment for biopsy of the abnormal liver lesions (Figure 3A and B) and enlarged lymph nodes (Figure 4A). During surgery, general foamy-like lesions were observed throughout the whole liver, and the ascites was faint yellow in color. The duration of this laparoscopic operation was 50 minutes. After completing this surgical treatment, the patient was discharged.

Figure 3 Diffuse lesions of Liver in the laparoscopic sights. A: Right liver lobel; B: Left liver lobe.

Figure 4 Histopathology and immunohistochemical analysis of indeterminate dendritic cell tumor in the lymph nodes. A: Histopathology picture of lymph nodes (×40); B: Positive CD1a expression (×100); C: Positive s100 expression (×100); D: Negative Langerin expression (×100); E: Negative CD3 expression (×100).

Histologic examinations revealed no tumor cells in the hepatic lesions. Some dendritic cells were found in the mesenteric lymph nodes. Immunohistochemical analysis revealed positive expression of CD1a and S100 (Figure 4B and C) in these dendritic cells. Moreover, there was no expression of Langerin or CD3 markers (Figure 4D and E). Finally, an indeterminate dendritic cell tumor was diagnosed in this patient.

TREATMENT

The patient exhibited cachexia after receiving a cycle of cyclophosphamide therapy.

OUTCOME AND FOLLOW-UP

At the last follow-up, she was then referred to a large medical center specializing in the management of rare diseases.

DISCUSSION

A rare case involving a female patient with IDCT who lacked skin lesions is reported. Importantly, the overall clinical development of this type of IDCT was recorded. The patient presented some lesions resembling cholangiocarcinoma, but the biopsy results confirmed the correct diagnosis-IDCT. Finally, this patient was sent to a medical center specializing in rare diseases.

A recent review reported that most patients with IDCT exhibit various papules or nodules in the skin[8]. IDCT can occur directly in other organs, including the spleen[5], pancreas[6], thoracic spine[9], muscle[10] and bile duct. IDCT can imitate other diseases, and therefore, the diagnosis of IDCT patients with abdominal lesions may be delayed. Performing a biopsy on potential IDCT lesions is the optimal means for early diagnosis. It took 2 years to reach the correct diagnosis by performing surgery for biopsy of the abdominal lymph nodes in this patient. The strong mimicry of IDCT was the key factor leading to the initial misdiagnosis of cholangiocarcinoma.

The mimicry of IDCT should be noted. In this patient, the IDCT lesions resembling hepatocarcinoma and bile duct cancer lesions had perplexed the physicians. Additionally, the negative results of examinations for hematological tumors in the bone marrow had puzzled the doctors, not to mention the lack of evidence for Mycobacterium tuberculosis. The increasing levels of CA-125 and γ-GGT suggested that the tumor originated from biliary system tissue. Importantly, histologic examinations of the patient’s ascites failed to provide useful evidence for the diagnosis of IDCT. Therefore, surgery was conducted for biopsy of the abdominal lymph nodes, and the patient was ultimately diagnosed with IDCT. Surprisingly, it took nearly two years until the biopsy was performed to make the correct diagnosis. Timely surgery for biopsy may lead to an earlier diagnosis of IDCT, as has been reported for the rapid diagnosis of IDCT lesions in the pancreas[6].

The clinical traits of IDCT are unclear. According to the results of previous studies[11], patients of any age, ranging from 12 to 90 years, can present with IDCT. Additionally, differences in sex distributions have rarely been reported. Therefore, early biopsy is even more important for early diagnosis. Early diagnosis is beneficial for timely treatment, although there is no standard treatment protocol for IDCT. Cases of IDCT patients without skin lesions are very rare, so treatment regimen data are lacking. Potential chemotherapeutic drugs include cyclophosphamide, prednisone, vincristine and methotrexate[8]. Some patients experience remission and relapse of lesions, although receiving chemotherapy[12]. However, the optimal treatment plan is still unknown. The differences in prognosis between IDCT patients with skin lesions and those without skin lesions are unclear. Our study revealed that the overall duration of the clinical course of this type of IDCT is approximately 3 years.

Therefore, conducting more collective and in-depth studies is critical for clarifying the pathological mechanism of IDCT. First, patients with IDCT should be sent to large specialized medical centers, such as the Peking Union Medical College Hospital[13]. One reason is that it will be more convenient to conduct related clinical trials. For IDCT, blood or tissue specimen information should be recorded and managed in detail in cohort studies. Therefore, full tissue biopsy is the first step. Some studies have reported that BRAF gene mutation analysis in indeterminate dendritic tumors might provide guidelines for targeted therapeutic approaches[14]. Alterations in ETV3-NCOA2 translocation could also be detected in IDCT patients[11]. Gene sequencing is a good tool for conducting further research on IDCT. However, a review showed that only six of all reported cases were tested for BRAF V600E gene mutations[11]. Therefore, collective management of IDCT patients may facilitate further studies.

In addition, the special biological effects of dendritic cells have received increasing attention, especially their role in transmitting information about tumor antigens to lymphocytes[7]. Usually, gene analysis for this tumor is the first step. Further histological and molecular biology studies of tumor cells from IDCT patients may reveal more interesting and key changes for tumor treatment. Additionally, sensitivity tests of some drugs for IDCT can be conducted based on the tumor cells[15]. Unfortunately, the ability to conduct related experiments is limited at our medical center, but we want to participate in more in-depth research on IDCT. Therefore, we have referred this patient to a large specialized medical center for better management.

CONCLUSION

It is very rare for patients without skin lesions to be diagnosed with IDCT. The strong mimicry of IDCT led to our patient being first suspected to have cholangiocarcinoma. Timely surgical biopsy can prevent misdiagnosis. The overall clinical course of patients with this type of IDCT is short, at only a few years. Therefore, cohort studies of this disease conducted at specialized medical centers might be interesting and cost-effective.