| Abstract|| |
Lymphangioleiomyomatosis (LAM) is a rare, genetically determined, progressive interstitial lung disease, which almost exclusively affects women, especially at the childbearing age. The initial symptoms and radiographic changes in a patient with LAM are always associated with the respiratory system. Here, we present a case of mediastinal and abdominal LAM of a 22-year-old male, where LAM cells are negative for human melanoma black-45 ( HMB-45). The report of this uncharacterized LAM case will make a significant contribution to the realization of LAM associated clinical features, diagnostic approaches, and its afterward treatments.
Keywords: Extrapulmonary, HMB-45 negative, lymphangioleiomyomatosis, man
|How to cite this article:|
Wang X, Su F, Zhou F, Feng M. Sporadic lymphangioleiomyomatosis with multiple atypical features: A case report and literature review. Indian J Pathol Microbiol 2018;61:94-7
|How to cite this URL:|
Wang X, Su F, Zhou F, Feng M. Sporadic lymphangioleiomyomatosis with multiple atypical features: A case report and literature review. Indian J Pathol Microbiol [serial online] 2018 [cited 2021 Oct 18];61:94-7. Available from: https://www.ijpmonline.org/text.asp?2018/61/1/94/228200
| Introduction|| |
Lymphangioleiomyomatosis (LAM) classically occurs in women of reproductive age, even in postmenopausal women. It is characterized by excessive proliferation of immature smooth muscle cells in the walls of airways, venules, and lymphatic vessels in the lung. In Europe and the United States, the occurrence rate of LAM is estimated to be about 1/1 million people. However, LAM occurs in up to 40% of women with the tuberous sclerosis complex (TSC), which defined as an autosomal dominant neurocutaneous syndrome. Pulmonary LAM can occur as part of the TSC. The occurrence of TSC involves two tumor supressor gene mutations: TSC1 on chromosome 9 and TSC2 on chromosome 16. Meanwhile, a tiny minority of women do not have TSC, which is sporadic LAM. Both sporadic LAM and LAM with tuberous sclerosis (TSC-LAM) are associated with mutations in tuberous sclerosis 1 genes. Usually, a patient with LAM will present with progressive dyspnea, spontaneous pneumothorax, chylous effusions, and hemoptysis according to observation. Through a combination of respiratory symptoms and computed tomography scanning, LAM is often misdiagnosed as asthma, chronic obstructive lung disease, or bronchitis. In cases of doubt, tissue biopsy is the gold standard for the diagnosis. Previous studies have shown LAM cells consistently stain positive for HMB-45, a monoclonal antibody for melanoma-associated antigen. In this case, we report a sporadic LAM with multiple atypical features, including male, extrapulmonary, and HMB-45 negative.
| Case Presentation|| |
A 22-year-old male patient presented with unprovoked right lower abdominal pain for 1 day. At the local hospital, the patient was initially misdiagnosed as acute appendicitis, and abdominal pain of the patient was relieved after anti-infection treatment. However, abdominal ultrasonography revealed abdominal multiple systic space-occupied lesions. Subsequently, the patient was transferred to the Department of Oncology, Zhongnan Hospital of Wuhan University. Special family history, particularly of tuberous sclerosis, histiocytosis, or chronic lung disease was denied in his self-report. Intravenous contrast-enhanced chest, abdomen, and pelvis computed tomography (Spiral computed tomography [CT]; Siemens, Munich, Germany) scans revealed a thin-walled cysts distributed in the right middle mediastinum [Figure 1]a, and multiple diffuse abdominal cysts, of which the biggest approached 20.2 cm × 15.7 cm × 9.1 cm [Figure 1]c. These low low-density cysts were slight homogeneous enhancement [Figure 1]d. Strikingly, imageological examination presented no obvious lung lesion [Figure 1]b.
|Figure 1: Intravenous contrast-enhanced chest, abdomen, and pelvis. (a) A thin-walled cysts distributed in the right middle mediastinum and (b) no obvious lung lesion. (c) The abdomen presented multiple diffuse abdominal cysts, the biggest measured 20.2 cm × 15.7 cm × 9.1 cm, and (d) these low-density cysts were slight homogeneous enhancement|
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Based on the observation of imageological examination, a laparotomy was performed to confirm the diagnosis and treat the disease. At the time of the operation, thin-walled cystic blebs were noted in abdominal cavity [Figure 2]a, and a mesenteric cystic mass covered with tiny “hills and valley” was located in the upper jejunum, approximately 20 cm × 15 cm × 9 cm in size [Figure 2]b. No metastatic lesions were detected in other organs. Consequently, the pathologically changed jejunum and abdominal cysts were successfully resected.
|Figure 2: Laparotomy showed (a) abdominal cavity is filled with thin-walled cystic blebs, and (b) a mesenteric cystic mass covered with tiny “hills and valley” is located in the upper of jejunum, approximately 20 cm × 15 cm × 9 cm in size|
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Postoperative pathological examination confirmed the diagnosis of LAM. Pathological section showed nodular proliferation of abnormal smooth muscle and cysts [Figure 3]. Immunohistochemistry (IHC) analysis showed strong reactivity for CD34 [Figure 4]a, DESM [Figure 4]b and smooth muscle actin (SMA) [Figure 4]c, mild reactivity for D2–D40 [Figure 4]e and negativity for Melan-A [Figure 4]d and HMB-45 [Figure 4]f. Since the patient refused to receive further treatments, no additional medical therapy was implemented after surgery. The patient recovered well and has no recurrence after a short-term follow-up.
|Figure 3: Hematoxylin and eosin staining showed nodular proliferation of abnormal smooth muscle and cysts (×100)|
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|Figure 4: Immunohistochemistry analysis (IHC, ×200). Immunohistochemistry showed strong reactivity for (a) CD34, (b) DESM and (c) smooth muscle actin, mild reactivity for (e) D2-40, and negativity for (d) Melan-A and (f) HMB-45|
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| Discussion|| |
LAM is a rare disorder of unknown etiology, linked with mutations in tuberous sclerosis genes, and angiomyolipomas primarily affecting the kidney. For the relationships among LAM, TSC, and angiomyolipomas, LAM and angiomyolipomas can occur as a part of TSC. Consequently, LAM can be classified into two types: Sporadic LAM and TSC-LAM. According to publication, half of the patients with S-LAM manifest angiomyolipomas free. Meanwhile, TSC-LAM shows more likely to accompany angiomyolipomas, and vice versa. Although many studies have confirmed that LAM spreads primarily through axil lymphatic channels, involving thorax, abdominal and pelvic cavity, the precise mechanism of this disease is unclear until now, and more further researches need to be performed.
Conventionally, LAM is a rare, slowly progressive lung disease that almost exclusively affects young women at reproductive age. The pulmonary disease is characterized by various symptoms, including dyspnea, pleural effusion, hemoptysis, and spontaneous pneumothorax. However, more extremely few cases have been reported. A few patients of extrapulmonary LAM with or without TSC are found, presenting with renal angiomyomas (a benign tumor), meningioma and abdominal LAM. In addition, few patients with extrapulmonary LAM have not pulmonary features, such as respiratory symptoms, lung function insufficiency, and pulmonary imaging changes. Although LAM almost exclusively affects women, some investigators have reported individual cases of LAM occurred in the male.,,,,, Moreover, previous studies have also suggested that LAM can occur relatively mild in men with TSC. We herein list other reported abnormal cases of LAM [Table 1]. Due to the rarity and complexity of LAM, many cases of pulmonary LAM are initially misdiagnosed as more common lung diseases, such as asthma, chronic obstructive pulmonary disease, or other cystic lung diseases, while the patients of extrapulmonary LAM can also be easily mistaken for other abdominal diseases, such as lymphoma cancer, ovarian tumor.
|Table 1: Major characteristics of other reported abnormal cases of lymphangioleiomyomatosis|
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The diagnosis of this case was not made until a pathological examination was performed after surgery. At present, the diagnosis of pulmonary LAM almost completely depends on progressive respiratory symptoms and pathognomonic appearance of pulmonary cysts by chest CT. Besides, serum vascular endothelial growth factor (VEGF) index may be a clinically useful diagnostic test for LAM since LAM cells can produce significant VEGF. However, abnormal LAM as our report without pulmonary features, presenting abdominal pain as the initial symptom, is very difficult to be diagnosed. Under these circumstances, pathological examination takes an irreplaceable role in the diagnosis of LAM. Two lesions characterize LAM, namely cysts and a multifocal nodular proliferation of immature smooth muscle cells (LAM cells). When the pathological features of LAM are not completely clear, IHC should be performed to assist the diagnosis. LAM cell is the precursor of the smooth muscle cell, which stains positive for several smooth muscle markers, including SMA and desmin, as well as melanocytic markers, such as Melan-A and HMB-45. The reactivity of HMB-45 is the hallmark of LAM and of greater help for the diagnosis of LAM. However, Jaiswal et al. is the first to report a case of female LAM with HMB-45 negative, just as our report. Although Fiore et al. have previously reported a male LAM case with HMB-45 negative, this finding is suspicious because of the absence of image about immunohistochemical staining with HMB-45 expression.
Currently, there is no curative treatment for the disease. Considering LAM almost exclusively affects women of reproductive age, some scientists suspect that LAM is associated with estrogen. Numerous basic research studies suggest that estrogen is a pivotal driving force in the development of LAM. Hormone therapy including progesterone supplementation, anti-estrogen measures and surgical oophorectomy have become the most widely used therapeutic regimens., However, Its exact mechanism of action remains unknown. Furthermore, complications including pneumothorax, progressive dyspnea and abdominal manifestations have become the key of the treatment of LAM. When managing abdominal LAM, surgical resection is an appropriate option for disease control and symptoms remission because of the uncertain behavior of this entity. Sometimes, lesion resection through surgery is also an appropriate option for disease control and symptoms remission. The patient also received complete resection and recovered well, which confirmed the validity of surgery. As for severe cases of pulmonary LAM, lung transplantation plays an important role.,
The prognosis of LAM is highly variable for different people. The 10-year survival rate of this disease is now about 70% through surgery and/or medical treatment. Some patients with LAM can keep stable for many years and thus obtain long-term survival. Previous studies have indicated that LAM turns to be worsen during pregnancy., With regard to pregnancy, decision should be made on consideration of the patient's actual situation. There is no known familial tendency for LAM. Although LAM is not malignant, some researches have shown that LAM cell can metastasize through axial lymphatics., Regular reexamination including pulmonary function test and thoracoabdominal enhanced CT is extremely necessary for the patients with LAM to prolong the moderate survival time further after rigorous surgery and/or medical treatment.
| Conclusions|| |
We herein present a rare case of sporadic LAM in a 22-year-old male without stigmata of TSC, which is located in the right middle mediastinum and abdominal cavity. More rarely, the current case is negative for HMB-45 expression. Taking into account these peculiar features, we believe this case may be a novel clinicopathologic subtype of LAM and help clinicians to advance their understanding of this rare disease.
Ethics approval and consent to participate
The study was approved by the patient and Ethics Committee of Zhongnan Hospital of Wuhan University and Informed consent was obtained from the patient.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
This research was supported in part by grants from Research Foundation of Health and Family Planning Commission of Hubei Province (grant number WJ2015MA010).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Johnson S. Rare diseases 1. Lymphangioleiomyomatosis: Clinical features, management and basic mechanisms. Thorax 1999;54:254-64.
Jaiswal VR, Baird J, Fleming J, Miller DS, Sharma S, Molberg K, et al.
Localized retroperitoneal lymphangioleiomyomatosis mimicking malignancy. A case report and review of the literature. Arch Pathol Lab Med 2003;127:879-82.
Carel H, Johnson S, Gamble L. Living with lymphangioleiomyomatosis. BMJ 2010;340:848.
McCormack FX. Lymphangioleiomyomatosis: A clinical update. Chest 2008;133:507-16.
Aubry MC, Myers JL, Ryu JH, Henske EP, Logginidou H, Jalal SM, et al.
Pulmonary lymphangioleiomyomatosis in a man. Am J Respir Crit Care Med 2000;162:749-52.
Kang HW, Kim CJ, Kang SK, Lee KS, Lee CS, Kim YH, et al.
Pulmonary lymphangioleiomyomatosis in a male. J Korean Med Sci 1991;6:83-5.
Wakida K, Watanabe Y, Kumasaka T, Seyama K, Mitani K, Hiraki T, et al.
Lymphangioleiomyomatosis in a male. Ann Thorac Surg 2015;100:1105-7.
Schiavina M, Di Scioscio V, Contini P, Cavazza A, Fabiani A, Barberis M, et al.
Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex. Am J Respir Crit Care Med 2007;176:96-8.
Kim NR, Chung MP, Park CK, Lee KS, Han J. Pulmonary lymphangioleiomyomatosis and multiple hepatic angiomyolipomas in a man. Pathol Int 2003;53:231-5.
Fiore MG, Sanguedolce F, Lolli I, Piscitelli D, Ricco R. Abdominal lymphangioleiomyomatosis in a man with Klinefelter syndrome: The first reported case. Ann Diagn Pathol 2005;9:96-100.
Department of Oncology, Zhongnan Hospital of Wuhan University, No 169, Donghu Road, Wuchang District, Wuhan 430071
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]